PHARMACEUTICAL SCIENCES

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3D Rendering of Geo-Spatial Data in XML/GML Using Python
(2012-06) Salisu, Aliyu
Geographic information (also called geo-information, spatial information or geospatial information) plays an increasingly important role in our society. Location-based services, applications for urban planning, disaster management systems rely on up-to-date geospatial data. Geo-spatial data as a major component of every Geographic Information System has been facing many challenges in its use including: portability, maintainability, interoperability, accessibility and unavailability of digital dataset. This work proposes a framework for the 3D rendering of Geo-spatial data in XML/GML which are MarkUp Languages that encodes Geo-spatial information in the Web. With our framework, we were able to extract Geo-spatial information from the satellite imagery of an area covered by the Ahmadu Bello University, Zaria, then store this information in a spatially enabled database interfaced with our Python engine which now renders this geo-spatial information in GML. The basic idea is to render this geographic information in a unique environment (the Web) that will make this data portable, accessible, maintainable and interoperable. The approach reveals interesting results as it was discovered that the framework with a little extension can be adopted to serve geographic data in other XML-base technologies capable of holding geographic information like City GML, X3D and KML.
ACTIVITIES OF SOME ANTIFUNGAL AGENTS AGAINST PHYTOPATHOGENIC YAM ROT FUNGI SPORES IN ZARIA, NIGERIA
(2011-08) CELESTINA, OTEGWU TEMILOLA
Postharvest deterioration has been a major problem associated with yam storage for both farmers and traders and it is caused mostly by micro-organisms especially fungi. The antifungal activity of some commonly used anti-dermatophytic agents (Fluconazole, Terbinafine Hcl, Ketoconazole, Sodium propionate and Griseofulvin) against phytopathogenic fungi such as Aspergillus flavus, Aspergillus niger, Penicillium citrinum and Rhizopus stolonifer spores were investigated. The sensitivity of phytopathogenic isolated fungi spores to test antifungal agents were carried out using zone of inhibition, Minimum Inhibition Concentrations (MICs), Minimum Fungicidal Concentrations (MFCs), Fractional Inhibitory Concentrations (FICs) and Fractional Fungicidal Concentrations (FFCs) to measure the antifungal activities of the test antifungal agents, their fungi toxic effects against A. flavus, A. niger, P. citrinum and R. stolonifer was found to be in the order of: Terbinafine Hcl > Fluconazole > Ketoconazole > Sodium propionate > Griseofulvin The in-vitro MICs of the antifungal agents for example Terbinafine Hcl against A. flavus, A. niger, P. citrinum and R. stolonifer were 1.0, 10.0, 1.0, and 50.0μg/ml respectively. This is an indication that R. stolonifer is the most resistant phytopathogenic fungal spores in this investigation against the observed potent antifungal agents in this study. The effects of fungicidal concentration of the different antifungal agents against viable test fungi spores number at different time interval showed rapid lethal effects. The six potential fungicides combination observed in this study, viz: Terbinafine Hcl, Fluconazole and Ketoconazole in combination each with either Sodium propionate or Griseofulvin displayed synergistic activity with value of FIC 0.19 to 0.83 against the test phytopathogenic fungal spores. The antifungal effects of evaluated fungicide combinations were observed to be stable at temperature ranges of 35-70ºC, but effect reduced as the temperature increased to 100 ºC. At acidic pH, there was general reduction in the antifungal effects of these combinations, but at neutral and alkaline pH the antifungal effects increased. Within six months storage of these combinations, antifungal effects were stable and sustainable. The in-vivo antifungal activity shows that these formulated fungicide combinations can be used to preserve yam as they inhibited Aspergillus niger and Rhizopus stolonifer (1.5 x 106cfu/ml) spores on sliced old and new yam.
ALKALOIDS OF THE AFRICAN RAUWOLFIA SPECIES OF THE SUB-SECTION OPHIOXYLANTHUS
(1978-11) Bamidele, Akinyemi Akinloye
The a l k a l o i d s of t h e Rauwolfia s p e c i e s have been reviewed and s p e c t r o s c o p i c methods of i d e n t i f i c a t i o n d i s c u s s e d. D e t a i l e d phytochemical i n v e s t i g a t i o n s have "been c a r r i e d out on t h e two s p e c i e s of t h e s e c t i o n Ophioxylanthus of P i c h o n ' s c l a s s i f i c a t i on of t h e genus Rauwolfia. In a l l , n i n e t y a l k a l o i d s were i s o l a t e d and t h e i r s t r u c t u r e s e l u c i d a t e d. R. v o l k e n s i i s t a p f root y i e l d e d t w e n t y - s i x a l k a l o i d s i n c l u d i ng two new compounds, t e t r a p h y l l i c i n e - 1 7 - O - a c e t y l and r a u v o l c i n i n e . The stem b a r k gave s e v e n t e e n a l k a l o i d s i n c l u d i n g t h e new a l k a l o id p r e - p e r a k i n e . Thirteen a l k a l o i d s were i s o l a t e d from t h e l e a v e s , four of which are new n a t u r a l p r o d u c t s i . e . m e t h o x y - p l e i o e a r p a m i n e , methoxyp l e i o c a r p a m i n e 2 : 7 d i h y d r o , methoxy-pleioearpamine N-oxide and v o l k e n s i n e . The a l k a l o i d p l e i o c a r p a m i n e and i t s d e r i v a t i v e s have not p r e v i o u s l y been i s o l a t e d from any Rauwolfia s p e c i e s. l\- o r e o g i t o n Mgf. root y i e l d e d t h i r t e e n a l k a l o i d s of which t h r ee have not been p r e v i o u s l y r e p o r t e d i n t h e p l a n t . The l e a v e s y i e l d ed t w e n t y - o n e a l k a l o i d s i n c l u d i n g f i v e new ones , akuammiline-5-formyl, o r e o g U, akuammiline 2 - d i h y d r o , d e a c e t y l akuammiline 2/4 - d i h y d r o and an i m p o r t a n t b i o g e n e t i c i n t e r m e d i a t e a l k a l o i d a d i r u b i n e a c e t a t e 19 : 20 dehydro. The i n t e r - r e l a t i o n s h i p of t h e i s o l a t e d a l k a l o i d s has been d i s c u s s ed and b i o s y n t h e t i c pathways proposed. The evidence o b t a i n e d concerning the a l k a l o i d s of t h e s e c t i o n Ophioxylanthus s p e c i e s has been used t o r e l a te t h e s e c t i o n chemotaxonomically to t h e o t h e r African Rauwolfia s e c t i o n s and t h e c l o s e l y r e l a t e d genus Cabucala.
THE AMELIORATIVE EFFECT OF ACACIA SIEBERIANA D.C. METHANOL ROOT BARK EXTRACT ON INDUCED LIVER INJURY AND ITS SUBCHRONIC TOXICITY PROFILE IN RATS
(2018-03) WATAFUA, Miriam
Acacia sieberiana D.C is traditionally used as a remedy for various ailments including hepatitis. The effect of methanol root bark extract of Acacia sieberiana (ASE) on paracetamol (PCM) - and bile duct ligation (BDL) –induced liver injury wereinvestigated in rats. Rats were divided into six groups (Groups I-VI) of 5 and 6 rats for PCM and BDL, respectively. For the PCM-induced liver injury study, animals were pre-treated with normal saline, silymarin (50mg/kg) and extract (250, 750, 1,500 mg/kg)for 7 days. After the last dose, liver injury was initiated by the administration of PCM (2g/kg). In BDL-induced liver injury study, 6 non-ligated but operated rats were used as control (Group I), Groups I and II received normal saline while Groups III-VI received silymarin (50mg/kg), the extract (125, 250 and 380 mg/kg), respectively, for 7 days. At the end of the experiment, blood and organs were obtainedfor biochemical and histological assay. Results showed the presence of carbohydrates, glycosides, triterpenes, cardiac glycosides, saponins, tannins, flavonoids and alkaloids. The LD50 values for oral and intraperitoneal routes of ASE were >5,000 and 1,300 mg/kg respectively. The subchronic toxicity study revealed that ASE significantly (P<0.05) reduced body weight when compared to the control and significantly (P<0.05) elevated ALP, whereas, serum urea and blood lymphocytes were significantly (P<0.05) increased at the 1500mg/kg dose group. The histology of the heart revealed no effect. However, the liver produced a dose-dependent hepatocellular necrosis and vacuolations. There was also lymphocyte hyperplasia and glomerular necrosis of the kidneys and alveolar congestion of the lungs. PCM significantly (P<0.05) elevated ALT, AST, direct Bilirubin and significantly (P<0.05) decreased total protein and albumin when compared to ASE. Whereas, ASE at 250 and 750 mg/kg was seen to significantly (P<0.05) decrease the levels of ALT and AST, while xix total protein and albumin were significantly (P<0.05) elevated in ASE-treated groups. However, direct bilirubin was significantly (P<0.05) decreased in silymarin group and 750 mg/kg ASE group. Furthermore, PCM significantly (P<0.05) decreased SOD and increased MDA when compared with ASE pre-treated groups. The histology revealed, PCM caused severe necrosis of the hepatocytes with vascular and sinusoid congestions but the impacts were mild with silymarin and lower doses of ASE pre-treated groups. The BDL–induced liver injury study revealed that ASE significantly (P<0.05) decreased AST level at lower doses and significantly decreased ALP level at higher doses. Likewise, ASE significantly (P<0.05) decreased direct and total bilirubin levels in silymarin and ASE treated groups. There was significant (P<0.05) elevation of SOD at lower ASE doses while GPx and CAT were significantly (P<0.05) elevated in ASE-treated groups. Furthermore, MDA was only significantly decreased at 125 mg/kg ASE group. Histology revealed that themorphology of liver tissue was preserved at 125 and 250 mg/kg ASE groups from BDL-induced moderate necrosis and vascular congestion. The study concludes that Acacia sieberiana is relatively non-toxic with acute administration and has hepatoprotective potentials on PCM- and BDL-induced liver injury at its lower doses but could be relatively toxic at its higher doses and/with prolonged use
AMELIORATIVE EFFECT OF RESVERATROL ON LEAD-INDUCED ORGAN TOXICITY IN WISTAR RATS
(2015-11) SALISU, Muhammad Highab
Resveratrol is a potent antioxidant found abundantly in grapes and in lesser quantities in peanuts, fruits and other food items. Dozens of reports have shown that resveratrol prevents or slows the progression of a wide variety of illnesses including cancer (colon and melanoma). The aim of this experiment was to investigate the ameliorative effect of resveratrol on lead-induced organ toxicity in wistar rats. The study employed wistar rats (150 - 250 g) which were administered carboxymethylcellulose 10 g/l (control), lead acetate solution (120 mg/kg), lead acetate solution (120 mg/kg) and succimer (10 mg/kg BW); lead acetate solution (120 mg/kg) and resveratrol (200 mg/kg); lead acetate solution (120 mg/kg) and resveratrol (400 mg/kg); and resveratrol alone (400 mg/kg) then administered lead acetate solution (120 mg/kg) daily for 2 weeks and considered as prophylactic group. All treatments were through the oral routes for different days. The acute toxicity of resveratrol was evaluated using the up and down method via oral routes in rats. The animal‟s body weights were recorded on days 1, 7 and 20. Also after animals were euthanized, relative organ weights were evaluated. Blood, plasma and organs samples were evaluated for blood lead levels (BLLs), heamatological analysis, biochemical analysis and histopathology. The LD50 was found to be above 5000 mg/kg. The results showed no significant (p > 0.05) change in body weight (BW) in resveratrol-treated group compared to the positive control group. Resveratrol-pretreated group showed improved BW compared to that of the positive control rats, although the difference was not significant (p > 0.05). There was significant (p < 0.001) decrease in BLLs of resveratrol-treated groups compared to both negative and positive control groups. No significant (p > 0.05) change was recorded for the liver function parameters viii and electrolytes concentration, when the resveratrol-treated rats were compared to negative and positive control groups. There was significant (p < 0.05) increase in platelet counts in resveratrol-treated group (392.33 ± 31.81) compared to both negative (219.50 ± 30.50) and lead acetate treated group (210.50 ± 24.99). No significant (p > 0.05) change was recorded for the other heamatological parameters, when the resveratrol-treated groups were compared to negative and positive control groups. In the histopathology, the toxic effect of lead recorded in liver, kidney, heart and brain in the positive control group were significant (p < 0.05) when compared to resveratrol-treated groups. The toxic effects caused by lead were reduced to minimal level in resveratrol-treated groups. In conclusion, resveratrol ameliorated the adverse effects induced by lead in male wistar rats. This suggests that resveratrol may contain pharmacological compounds that could be useful in treatment of lead poisoning.
ANALGESIC AND ANTI-INFLAMMATORY EFFECTS OF METHANOL EXTRACT AND FRACTIONS OF LAGGERA AURITA LINN F (COMPOSITAE) IN MICE AND RATS
(2014-08) SHEHU, AISHATU
The plant Laggera aurita is an annual or biennial herb of widespread in dry waste places from across Senegal to Southern Nigeria. The plant has been reportedly used for medicinal purposes including treatment of rheumatic pain, healing of cuts and bruises, and as a last resort to phagedenic and chronic ulcers. The present study investigated the analgesic and anti-inflammatory properties of the methanol extract, saponin and flavonoid fractions of the plant in mice and rats. Acetic acid induced writhes test, thermally induced pain and formalin induced inflammation models in rodents were used to evaluate the antinociceptive properties of the extracts. Phytochemical and acute toxicological screenings were also conducted. The median lethal dose was above 5000 mg/kg in mice and rats for both the methanol extract and the fractions. The histological changes at 5000 mg/kg were slight glomerular necrosis and tubular damage in the kidney, slight vascular congestion, kupfer cell hyperplasia and lymphocyte hyperplasia in liver, lymphocyte hyperplasia on spleen, slight alveolar congestion on lungs and moderate erosion of stomach epithelium on stomach. The methanol extract, saponin and flavonoid fractions at doses of 200, 400 and 800 mg/kg significantly (p<0.05) inhibited the acetic acid induced abdominal writhes in mice dose dependently. Both the extract and fractions at 800 mg/kg showed better activity than 20 mg/kg piroxicam. The methanol extract, saponin and flavonoid fractions of Laggera aurita also significantly (p<0.05) and dose dependently increased the reaction time in the thermally induced pain model. The methanol extract (800 mg/kg) and saponin fraction (400 and 800 mg/kg) showed better activity when compared to the standard morphine (5 mg/kg) at 60, 90 and 120 minutes. Naloxone, a non specific opioid antagonoist blocked the analgesic effect observed with the thermally induced pain model in mice for both the methanol and viii fractions. The methanol extract and saponin fraction of Laggera aurita significantly (p<0.05) decreased formalin induced paw edema in a dose dependent manner. The saponin fraction (800 mg/kg) exhibited better anti-inflammatory effects than ketoprofen (10 mg/kg), the standard anti-inflammatory drug used. These findings suggest that the methanol extract, saponin and flavonoid fractions of the plant Laggera aurita possess analgesic and anti-inflammatory activities that justify the ethnomedical use in the treatment of painful and inflammatory conditions by the herbal practitioners.
ANALGESIC AND ANTI-INFLAMMATORY STUDIES ON METHANOL ROOT EXTRACT OF ANDROPOGON GAYANUS KUNTH (POACEAE) IN MICE AND RATS
(2016-09) UMAR, Suleiman Zandam
The plant Andropogon gayanus is employed in herbal medicine for the treatment of various disease conditions. The dried root of the plant is soaked in milk and taken for the treatment of postpartum pain and bronchitis in North-west Nigeria. In this study the methanol root extract of the plant was screened for phytochemical constituents followed by acute toxicity studies in mice and rats. Analgesic activity was evaluated using acetic acid-induced writhing test in mice, hot plate test in mice and formalin-induced pain test in rats whereas anti-inflammatory activity was evaluated using Carrageenan-induced paw oedema model in rats. Acetic acid induced writhing test in mice is employed in the screening of the involvement of opioid receptors, ATP dependent potassium ion (K+ATP) channels and α2-adrenergic receptors in the mechanism of analgesia. Preliminary phytochemical screening revealed the presence of glycosides, saponins, flavonoids, alkaloids and tannins amongst others. Toxicity studies in both rats and mice revealed oral LD50 value of > 5000 mg/kg and intraperitoneal LD50 value of 1265 mg/kg. The extract at doses of 250, 500 and 1000 mg/kg (p.o) produced a significant (p < 0.05) inhibition of writhing induced by acetic acid. In the hot plate test the extract at all doses increased the reaction time at different intervals; the difference when compared to the negative control group and to the value at time zero was statistically significant (p< 0.05). In formalin-induced pain test, the extract exhibited significant (p< 0.05) analgesic and anti-inflammatory activities in first and second phases of the formalin test respectively. The extract significantly (p< 0.05) reduced oedema induced by carrageenan in rats. Naloxone, a non specific opioid antagonist significantly (p< 0.05 and p< 0.01) blocked the analgesic effect observed with administration of acetic acid in the methanol extract and morphine treated mice respectively. However, glibenclamide (K+ATP channel blocker) did not inhibit the analgesic effect of the extract, neither did the α2 receptor blocker, yohimbine. This study suggests that the root of Andropogon gayanus contains bioactive constituents that possess analgesic and anti-inflammatory effects, the former supposedly being mediated through the action of opioid receptors.
ANALGESIC, ANTI-INFLAMMATORY AND OTHER PHARMACOLOGICAL ACTIVITIES OF METHANOL LEAF EXTRACT OF OLAX SUBSCORPIOIDEA OLIV (OLACACEAE) IN LABORATORY ANIMALS
(2016-06) ODOMA, Saidi
Synthetic analgesic and anti-inflammatory drugs have major side effects such as constipation, nausea and vomiting, sedation and mental clouding, etc.,which have significantly limited their use.There is therefore, an intensification of search for newer analgesic and anti-inflammatory agents from the huge array of medicinal plant resources with better efficacy and fewer side effect profiles. Medicinal plants such as Olax subscorpioidea have been used traditionally for the management of pains, inflammatory diseases, yellow fever, cancer and rheumatism. The study aims at establishing the analgesic and anti-inflammatory potentials of methanol leaf extract of Olax subscorpioidea; and elucidating its possible mechanism of actions. The methanol extract and its fractions were subjected to phytochemical screening; oral and intraperitoneal median lethal dose (LD50) determination; evaluation of analgesic activities using acetic acid-induced writhing, formalin induced pain and hot plate tests in mice; and evaluation of anti-inflammatory activity using carrageenan-induced hind paw oedema model in rats. The doses (oral) used for these studies were 250, 500 and 1,000 mg/kg for the methanol extract, residual aqueous and butanol fractions; while doses of 150, 300 and 600 mg/kg were used for the hexane fraction. The residual aqueous and butanol fractions (1,000 mg/kg, orally) were subjected to sub-acute inflammation studies using cotton-pellet induced granuloma in rats; also the concentrations of inflammatory cytokines in the tissue exudates of rats following carrageenan induced paw oedema was investigated. The roles of opioidergic, (α1, α2 and β)-adrenergic, serotonergic, ATP-sensitive potassium channels and nitric oxide-l-arginine pathways in the analgesic activities of the butanol fraction (1,000 mg/kg, oral) were further investigated. Results of the preliminary phytochemical screening of the methanol extract and the fractions indicated the presence of various phytochemicals such as vii carbohydrates, cardiac glycosides, tannins, flavonoids, alkaloids, saponins, steroid and triterpenes. The oral LD50 of the methanol extract, residual aqueous and butanol fractions was estimated to be greater than 5,000 mg/kg in both rats and mice; that of hexane fraction was estimated to be 2,200 and 3,800 mg/kg in mice and rats respectively. The intraperitoneal LD50 in mice was estimated to be 3,800 mg/kg for the methanol extract; 2,200 mg/kg for the residual aqueous fraction and 1,300 mg/kg for butanol and hexane fractions; it was estimated in rats to be 3,800 mg/kg for the methanol extract, residual aqueous and butanol fractions; and 2,200 mg/kg in the hexane fraction. The acetic acid induced writhes and the formalin induced pain licking effect were significantly (p<0.05, p<0.01 and p<0.001) reduced by the methanol extract and the fractions in a dose-dependent manner. The thermal pain latency was also significantly (p<0.05, p<0.01 and p<0.001) increased by the methanol extract and its fractions (except hexane fraction). The paw oedema was also significantly (p<0.05, p<0.01 and p<0.001) reduced by the methanol extract and the fractions across the time. The residual aqueous and butanol fractions (1,000 mg/kg) significantly (p<0.01 and p<0.001) reduced granuloma formation in the cotton pellet-induced granuloma studies in rats. The residual aqueous and butanol fractions significantly (p<0.05 and p<0.01) decreased the concentrations of vascular endothelial growth factor (VEGF); the butanol fraction significantly decreased ((p<0.05) concentrations of epidermal growth factor (EGF) and interleukin-1α (Il-1α). The residual aqueous and butanol fractions also significantly (p<0.05 and p<0.01) increased the concentration of Il-1β, IL-5 and interferon-γ (IFN-γ) while the residual aqueous fraction significantly(p<0.05) increased the concentration of IL-6 in the rats‘ paw tissue exudates. The pretreatment of mice with l-arginine and metergoline significantly (p<0.01 and p<0.05, respectively) decreased the analgesic effect of the butanol fraction; while pretreatment with viii naloxone, prazosin, yohimbine, propranolol and glibenclamide,each, had no significant effect on its analgesic activity. The results of the studies revealed that Olax subscorpioidea possesses marked analgesic and anti-inflammatory activities; the anti-inflammatory activity is mediated via the inhibition of pro-inflammatory cytokines such as IL-1α, IL-1β, VEGF and EGF and/or via the stimulation of the synthesis of anti-inflammatory cytokines such as IL-5, IL-6 and IFN-γ. These results also suggest the possible involvement of serotonergic and nitric oxide pathways in the analgesic effect of Olax subscorpioidea.
ANALGESIC, ANTI-INFLAMMATORY AND TOXICITY STUDIES ON METHANOLIC LEAF EXTRACT OF ROTHMANNIA LONGIFLORA SALISB (RUBIACEAE) IN RATS AND MICE
(2011-09) MALLAM, DANJUMA.
ABSTRACT The herbalists in several African Countries have used Rothmannia longiflora decoctions as febrifugal and analgesic agent. The present study examined the analgesic, anti-inflammatory and toxicological profile of the methanolic extract of the plant in experimental animals. The preliminary phytochemical screening of the methanolic leaf extract of R.longiflora was carried out and revealed the presence of cardiac glycoside, steroids/terpenoids, tannins, saponins, flavonoids and carbohydrates. The acute toxic effect (median lethal dose values (LD50) of methanolic leaf extract of Rothmannia longiflora was carried out using Lork’s method in intraperitoneal and oral routes in mice and rats and were found to be above 5000mg/kg body weight. The anti-nociceptive effects of the extract was studied using acetic acid induced writhing test in mice, hot plate test in mice and formalin induced pain in rats. The anti-inflammatory effect was studied using Carrageenan induced paw oedema in rats. The extract at doses of 50-1000mg/kg significantly (P<0.05) inhibited the number of acetic acid-induced abdominal writhes in mice dose dependently. The highest inhibition of abdominal constriction (64.9%) observed at 1000mg/kg was greater than that of piroxicam (61.5%), the standard non-steroidal analgesic and anti-inflammatory drug used in the study. The methanolic leaf extract at doses of 250-1000mg/kg R. longiflora significantly (P<0.05) and dose-dependently protected the mice against thermally induced pain stimulus in mice but there was no significant thermal protection with the dose of 50mg/kg. The 500 and 1000mg/kg doses of R.longiflora extract offered more than 100 and 200% respectively while the standard drug (Morphine sulphate) offered more than 300% protection against thermally induced pain stimulus in mice. vi There was no significant inhibition of both the neurogenic pain (early phase) and inflammatory pain (late phase) at 50mg/kg and 250mg/kg doses of the extract. However, there was significant (P<0.05) inhibition of both the neurogenic (early phase) and inflammatory (late phase) pain dose dependently at 500mg/kg and 1000mg/kg with highest inhibition at 1000mg/kg (53.33%). The significant (P<0.05) inhibition of the standard drug (Morphine sulphate) at the late phase was 46.67%; this doubled that of the early phase which was 20%. The methanolic leaf extract of R.longiflora significantly (P<0.05) inhibited Carrageenan induced paw oedema at doses of 250mg/kg; 500mg/kg and 1000mg/kg dose-dependently. There was no significant inhibition at dose of 50mg/kg. The percentage anti-inflammatory effects at the peak of the Carrageenan-induced oedema at the third hour were; 39.39%, 51.52%, 63.63% at respective doses of 250mg/kg, 500mg/kg and 1000mg/kg compared to 69.70% for Piroxicam 20mg/kg (the standard anti-inflammatory drug) Renal function test showed no statistically significant difference (P>0.05) of the levels of Sodium (Na+), Potassium (K+), Chloride (Cl-) ions, Urea and Creatinine compared to that of the control at the end of 30 days (sub-chronic) and 90 days (chronic) studies. In liver function test, there was no statistically significant difference (P>0.05) in the levels of AST, ALT, and ALP enzymes in all the treated groups compared to the control group after the 30 days studies. However, there was statistically significant difference with 500mg/kg and 1000mg/kg after the 90 days treatment. The Histopathological study showed no observable gross lesions during the periods of subchronic and chronic studies. vii These findings suggest that methanolic leaf extract of R.longiflora possesses analgesic and anti-inflammatory potentials/effects that justify the ethnomedical use of the plant in the treatment of painful and inflammatory conditions by the herbal practitioners. In addition, the results of toxicity studies showed that the extract is non-toxic to the kidneys and the heart during the sub-chronic and chronic toxicity studies however; mild fatty change was observed with 500mg/kg in the liver after the chronic studies.
ANALYSIS OF SERUM CALCIUM AND PHOSPHORUS IN RICKETS AND NON RICKETS CHILDREN OF GONIN-GORA, KASO AND JANKASA COMMUNITIES IN KADUNA STATE
(2011-03) OKPE, INUWA
The beginning of the 20th century witnessed the epidemic of nutritional rickets among children in many countries of Asia, North America, Northern Europe and Africa. Nutritional rickets remain a problem in developing countries despite a decline in the prevalence of the condition in developed countries. Prevalence of rickets among infants and young children is high in Nigeria and in Gonin-Gora, Jankasa and Kaso in particular. It was therefore imperative to evaluate some biochemical parameters in rickets disease prevalence areas of Kaduna state namely: Gonin Gora, Jankasa and Kaso. This study aimed at determining the serum levels of calcium and phosphorus together with the levels of associated biochemical parameters for the affected family member in these communities; as an investigation into the scourge of rickets. Randox Diagnostic test kit was used to determine the serum levels of calcium and urea while creatinine and phosphorus serum levels were measured using Agappe Diagnostic kit, serum sodium and potassium levels were determined using flame photometric method. The results obtained showed that serum calcium levels were low with mean values of 2.29± 0.01 S.E.M., 2.34+ 0.01 S.E.M and 2.24 ± 0.01 S.E.M in Gonin Gora, Jankasa and Kaso respectively compared with the 2.25-2.75 mmol/l normal limit. Phosphorous levels were toward the upper limit with mean values of 1.48 ± 0.02 S.E.M and 1.68 ± 0.02 S.E.M in Gonin gora and Jankasa respectively; compared with the normal limit of 0.8-1.9 mmol/l. However the mean serum calcium for rickets children from Kaso community (2.19 ± 0.03S.E.M) was below the normal range value of (2.25-2.75mmol/dL). None of the differences in measured levels was statistically significant. Rickets among rural children has been reported to be attributed to low serum calcium levels. The low serum levels of calcium and high serum phosphorus levels could be the major causes of the disease in these settlements especially during the period of the children growth. Also when the mean biochemical vii parameters for Gonin-Gora, Jankasa and Kaso were compared, the results showed that calcium levels was much more significantly reduced in Kaso compared with the other two communities, and this could be the reason why more rickets children were found in Kaso compared to Gonin-Gora and Jankasa. The results of influence of sex among the rickets and non rickets males and females children showed that, sex had no significant influence in the parameters of rickets male and females children living in Gonin-Gora, Jankasa and Kaso communities. In conclusion, the concentrations of serum calcium for rickets children were at the lower limit of normal range while the concentration of serum phosphorus were at the higher limit of the normal range which can be attributed to rickets disorder among children.
ANTHRACENE DERIVATIVES IN TISSUE CULTURE OF SOME NIGERIAN CASSIA SPECIES
(1983-06) RAI, PREM PRAKASH
This study was undertaken to determine the nature and quantity of anthraquinones produced in callus cultures of four Nigerian species of Cassia: C. nodosa Roxb., c. alata L., .C. occidentalis L. and C. podocarpa Guill. 4 Perr. A visual selection procedure for a high yielding anthraquinone cell line from callus cultures of C. podocarpa was attempted for the first time. The use of plant tissue culture for secondary product biosynthesis, particularly in plants of pharmaceutical importance, holds promise for the controlled production of plant constituents. In all of the Cassia cultures studied, only hydroxyanthraquinones, anthrones, dianthrones, and anthraquinone monoglycosides were produced and the most pharmacologically active dianthrone glycosides based on rhein were particularly absent. Callus cultures from seedling hypocotyls and cotyledons of Cassia nodosa,
ANTI-DIARRHOEAL AND SUBCHRONIC TOXICITY STUDIES ON METHANOLSTEM BARK EXTRACT OF IRIVINGIA WOMBOLU VERMOESEN (IRVINGIACEAE) IN LABORATORY ANIMALS
(2018-10) UHOMOIBHI, Lucia Onoselumhen
Irvingia wombolu is one of the herbal plants used as food for its nutritional values. It is also used as medicinal plant in the south-south and south-eastern part of Nigeria for the management of diarrhoea and other ailments. Although these medicinal plants are believed to be harmless with their utilization, scarcity of scientific evidence on the claimed pharmacological activities of this plant is an issue of concern. This study was aimed at evaluating the antidiarrhoeal and subchronic toxicity studies of methanol stem bark extract of I. wombolu (MEIW) in laboratory animals. Preliminary phytochemical screening, acute and sub-chronic toxicity, in vivo antidiarrhoeal and isolated tissuestudies were carried out according to standard methods. Doses of 500mg/kg, 1000mg/kg and I500mg/kg were used for the in vivo antidiarrhoeal studies. Preliminary phytochemical screening revealed the presence of saponins, steroids/triterpenes, flavonoids, tannins, alkaloids, cardiac glycosides, terpenoids and carbohydrates whereas anthraquinones was absent. The oral median lethal dose (LD50) of the extract in mice was estimated to be greater than 5000 mg/kg. In the subchronic toxicity study, the extract did not produce significant changes on body weights and the relative organ weights of treated rats when compared with control. The extract significantly (p≤0.05) decreased only the white blood cell (WBC) and neutrophils count among the haematological parameters assessed. The extract also significantly (p≤0.05) increased ALP and sodium while AST, ALT, TP, bilirubin, potassium, bicarbonate, chloride, urea, creatinine and albumin showed no significant difference when compared with the control. Histopathological findings indicated that there were some levels of liver injury characterized by centrilobular necrosis and mild hepatocytes vacoulation. The kidney exhibited mild distortion of tubular epithelial cell and widening of the bowman capsule within the glomerular at doses of 500 and 1000 mg/kg with the adhesion of intestinal villi. Results obtained from the castor oil and magnesium sulphate sulphate-induced diarrhoea models indicated that MEIW produced statistically significant inhibition of diarrhoea in both models with reduction of wet faeces (p≤0.05). In the castor oil-induced enteropooling model, MEIW demonstrated an anti-enteropooling effect by reducing significantly (p≤0.05) the volume of intestinal content in a dose-dependent way. In the gastrointestinal transit of charcoal meal model, the movement (transit) of charcoal meal along the intestinal tract of mice treated with the extract of I. wombolu (MEIW) was delayed. With increasing doses of the extract, the peristaltic index decreased significantly (p≤0.05) in all as compared to the negative control. In the guinea pig ileum, the extract produced a marked relaxatory effect on the tissue. Graded concentrations of the extract, produced a reduction in the tone and rate of the spontaneous contraction of rabbit jejunum. Also atropine in synergy with the extract blocked completely the stimulant effect of the rabbit jejunum, this indicates that the extract possess some anticholinergic-like properties. It can be concluded that, the extract is relatively safe with minor histopathological changes in vital organs with significant antidiarrhoeal effect.
ANTIBACTERIAL ACTIVITY OF THE LEAF EXTRACTS OF ALCHORNEA CORDIFOLIA (Euphorbiaceae) AGAINST ISOLATES FROM PATIENTS WITH RESPIRATORY TRACT INFECTION IN AHMADU BELLO UNIVERSITY TEACHING HOSPITAL ZARIA, NIGERIA
(2016-12) YUSUF, Isaiah
Many bacterial species have been reported to develop resistance to antibiotics commonly prescribed for respiratory tract infections. Therefore, the need to search for natural products for remedy of this problem cannot be overemphasized. One hundred and eighty (180) specimens were collected from throat (68) and ear swabs (57) as well as sputum (55) from patients with respiratory tract infection in Ahmadu Bello University Teaching Hospital Zaria, Nigeria. Isolation and identification of the bacterial isolates were carried out using standard microbiological methods. MicroGen identification kit was used for confirmatory identification of the isolates. The ethanol and aqueous extracts of Alchornea cordifolia was carried out using cold maceration extraction method. Agar well diffusion, agar dilution and spread plate methods were employed to determine the zone of inhibition, minimum inhibitory concentration, minimum bactericidal concentration and rate of kill respectively.The aqueous extracts was fractionated using column chromatography. Thin layer Chromatography method was used to identify the phytochemical constituents of the active fraction F2. The bacterial isolates identified were Staphylococcus aureus (7), Pseudomonas aeruginosa (2), Klebsiella pneumoniae (2), Escherichia coli (1) and Streptococcus spps (5). The two extracts showed broad spectrum of activity but the aqueous extract had larger zones of inhibition ranging from 32. 5 mm – 11. 5 mm and lower M.I.C and M.B.C values ranging from 5 mg/ml – 20 mg/ml. The fractionation of the aqueous extract gave thirty five (35) fractions but after pooling together of similar ones, Seven (7) different fractions were obtained. The M.I.C of the fractions showed that F2 had the lowest M.I.C values against all the isolates and better antibacterial activity. The F2 fraction had M.I.C values that ranged between 2.5 – 5 mg/ml against S. aureus and 5 – 10 mg/ml against Strep. spp. The death/survival rate showed that at 1440 minutes, M.I.C concentration of 2.5 mg/ml of F2 had 100 % kill; there was reduction in surviving cells with both the Sub-M.I.C concentration of 1.25 mg/ml and amoxicillin clavulanic acid 30 μg/ml against S. aureus (T38) isolate. A total kill was observed at 240 minutes, with M.I.C concentration of 5 mg/ml and at 1440 minutes, with Sub-M.I.C concentration of 2.5 mg/ml against Klebsiella pneumoniae (S16). There was a decrease in the number of surviving cells in the positive control and increase in the number of surviving cells with time in the negative control. The TLC based phytochemical screening of F2 fraction revealed the presence of phenolic compound and flavonoid as secondary metabolites. This study has justified the traditional use of Alchornea cordifolia leaf extracts in the treatment of respiratory tract infection caused by bacteria.
ANTIBIOGRAM OF UROPATHOGENIC BACTERIA ISOLATED FROM PATIENTS IN SOME HOSPITALS IN BIRNIN KUDU, JIGAWA STATE, NIGER
(2016-08) KACHALLAH, Mohammed
Urinary tract infection (UTI) is a common infection of human being and if untreated could lead to serious complications. This study was conducted to investigate the antibiotic susceptibility pattern of uropathogens from patients in two hospitals in Birnin kudu, Jigawa State, Nigeria. In this study, the antibiotic resistance profile and the plasmid profile of some multi-antibiotic resistant bacteria isolated from urine samples of patients from Birnin kudu community in North-west, Nigeria were analysed. Rapid diagnostic kit systems were used in identification of the isolated bacteria and agar disc diffusion technique was used for the determination of antibiotic susceptibility profiles of the isolated bacteria. Presence of β- lactamase was determined using standardized β-lactamase identification sticks while acridine orange was used for curing of multidrug resistant isolates. The cultures of some multi- antibiotic resistant isolates irreversibly lost their antibiotic resistance with acridine orange treatment, which suggests that the resistant genes could be harboured in the plasmids. The result showed that 94.3% of the isolates were resistant to Ampicillin, Amoxycillin-clavulanic acid (71.5%), Ceftriaxone (35.4%), Cefuroxime (57.3), Cotrimoxazole (73.1%), Nitrofurantoin (24.6%), Chloranphenicol (36.9), Doxycycline (58.0%), Ciprofloxacin (60.0%) and Gentamicin (61.2%). Out of 36 isolates tested for presence of β- lactamse, 66.1% possessed β- lactamases. Plasmid profile studies revealed the presence of plasmid of size range 5184.8kb – 5673.9bp. .
ANTIBIOGRAM OF UROPATHOGENIC BACTERIA ISOLATED FROM PATIENTS IN SOME HOSPITALS IN BIRNIN KUDU, JIGAWA STATE, NIGERIA.
(2016-08) KACHALLAH, Mohammed
Urinary tract infection (UTI) is a common infection of human being and if untreated could lead to serious complications. This study was conducted to investigate the antibiotic susceptibility pattern of uropathogens from patients in two hospitals in Birnin kudu, Jigawa State, Nigeria. In this study, the antibiotic resistance profile and the plasmid profile of some multi-antibiotic resistant bacteria isolated from urine samples of patients from Birnin kudu community in North-west, Nigeria were analysed. Rapid diagnostic kit systems were used in identification of the isolated bacteria and agar disc diffusion technique was used for the determination of antibiotic susceptibility profiles of the isolated bacteria. Presence of β- lactamase was determined using standardized β-lactamase identification sticks while acridine orange was used for curing of multidrug resistant isolates. The cultures of some multi- antibiotic resistant isolates irreversibly lost their antibiotic resistance with acridine orange treatment, which suggests that the resistant genes could be harboured in the plasmids. The result showed that 94.3% of the isolates were resistant to Ampicillin, Amoxycillin-clavulanic acid (71.5%), Ceftriaxone (35.4%), Cefuroxime (57.3), Cotrimoxazole (73.1%), Nitrofurantoin (24.6%), Chloranphenicol (36.9), Doxycycline (58.0%), Ciprofloxacin (60.0%) and Gentamicin (61.2%). Out of 36 isolates tested for presence of β- lactamse, 66.1% possessed β- lactamases. Plasmid profile studies revealed the presence of plasmid of size range 5184.8kb – 5673.9bp. .
ANTIBIOTICS SUSCEPTIBILITY AND MOLECULAR CHARACTERIZATION OF CLINICAL ISOLATES OF E. coli FROM AHMADU BELLO UNIVERSITY TEACHING HOSPITAL SHIKA, ZARIA
(2011-12) IGWE, James Chibueze
Antimicrobial drug resistance is a global challenge with the emergence of resistant bacterial strains worldwide. This study was conducted to determine the incidence of E. coli in ABUTH Shika, Zaria (from March 2011 to February 2012), their antibiotics susceptibility pattern, molecular characterization and possible presence of E. coli serotype O157:H7. Clinical isolates of E. coli from inpatients and outpatients were collected and cultured on eosin methylene blue to obtain pure cultures. A retrospective analysis of records of the Medical Microbiology unit for the same period (March 2011 to February 2012) was carried out. The incidence of E. coli isolates in clinical samples was found to be 50% in stool, 26.7% in urine, 13.3% in blood, 6.6% in urogenital and 3.3% in wounds. The retrospective analysis of the prevalence of E. coli associated infections in ABUTH Shika, showed that out of the 751 patients bio-data evaluated, female patients were mostly infected 62.3%(468) compared with male patients 37.4%(281). Of the 751 patients bio-data evaluated, 150 isolates were collected and 60 isolates were confirmed as E. coli. The antibiotic susceptibility profile of clinical isolates of E. coli to fourteen (14) commonly prescribed antibiotics in the treatment of E. coli associated infections showed that 76.7% of the isolates were resistant to ceftazidime, 78.3% to amoxicillin-clavulanic acid, 70% to ampicillinsulbactam, 56.7% to tetracycline, 43.3% to cefalexin, 41.7% to nalidixic acid, 36.7% to amoxicillin and 30% to cefuroxime. The isolates were also found to be sensitive to ceftriaxone (88.3%), gentamicin (78.3%), chloramphenicol (78.3%), ciprofloxacin (71.7%), nitrofurantoin (78.4%), ofloxacin (73.3%). Higher percentage (80%) of the isolates were multidrug resistant (MDR), 11.7% were extensively drug resistant (XDR). Statistical analysis at p value < 0.05, showed a significant difference in the level of resistance expressed by E. coli from different clinical samples. At MARI ≥ 0.3, 71.6% of the patients showed a frequent use of the antibiotics usually prescribed in the hospital for E. coli infections. The high minimum inhibitory concentration (μg/ml) of amoxicillin–clavulanic acid and ceftriaxone to the transconjugants of the multidrug resistant E. coli showed that the resistance exhibited was plasmid encoded. The extended spectrum β-lactamase (ESBLs) using double disc diffusion method showed that of the 10 isolates tested, all were resistant to amoxicillin-clavulanic acid, 7(70%) to ceftazidime, 5(50%) to ceftriazone and cefpodoxime. Seventy percent 7(70%) of the 10 selected multidrug resistant clinical isolates were ESBLs positive; a ≥ 5mm increase in zone diameter for either antibiotics compared to its zone when tested alone, while 30% (3) of the selected isolates showed production of AmpC gene. E. coli serotype O157:H7 was isolated in 11(18.3%) of the 60 confirmed E. coli isolates (that is, 36.7% (11) of the stool isolates (30) were E. coli serotype O157:H7, while other serotypes in stool isolates amounted to 63.3%). Hetero-resistant isolates of E. coli (small colonies variant, found within the diameter of the zone of inhibition of cefoxitin) showed a far higher resistance to some tested antibiotics than that of their parental clinical isolates. Using molecular characterization by polymerase chain reaction (PCR), the ESBLs encoding genes, TEM, SHV and OXA and plasmid bands were detected in the multidrug resistant isolates, and in line with documented works, this suggests that these genes were plasmid encoded. E. coli expressing ESBLs and AmpC enzyme are present in E. coli isolated from ABUTH, Shika, Zaria. These suggest that patients with infections associated with E. coli producing ESBLs and AmpC enzyme may have complication in therapy and limited treatment options, which will lead to higher mortality rate, high economic burden and longer hospital stays
ANTIBIOTICS SUSCEPTIBILITY STUDIES OF SOME BACTERIAL ISOLATES FROMPACKAGED MILK MARKETED IN ZARIA, NIGERIA
(2012-11) DAMIAN, UMOFIA INIMFON.
ABSTRACT Milk contamination with antibiotic resistant bacteria can be a major threat to public health, as the antibiotic resistant determinants can be transferred to other pathogenic bacteria potentially compromising the treatment of severe bacterial infections. This study was conducted to investigate the antibiotics susceptibility of bacterial isolates frompackaged milks marketed in Zaria. Two hundred packaged milk samples were bought from five locations (forty samples from each) in Zaria. Isolation and identification of the bacteria specieswere carried out using standard microbiological procedures. Antibiotics susceptibility of the isolates was determined using a panel of 12 antibiotics by disc diffusion method following Clinical Laboratory Standard Institute guidelines. Minimum Inhibitory Concentration (M.I.C.)was determined using agar plate dilution method.Conjugative studies were carried out with multiple antibiotics resistant isolates from milk samples. The resistant isolates were subjected to DNA isolation and agarose gel electrophoresis. The result obtained showed that the major contaminants of milk products analysed were Pseudomonas sppclosely followed by Enterobactersppand Escherichia coli and the overall contamination level of bacterial isolates in this study was 76.5%. One hundred and fifty-three bacterial isolates were identified from the milk sample, 27.5% were obtained from the first brand of milk sample, 21.6% from the second brand, 12.4% from the third brand and 38.6% from the fourth brand of milk samples. Susceptibility result showedthat high percentage of isolates were resistant to cloxacillin (99.35%), erythromycin (98%), amoxicillin (83.01%), chloramphenicol (83%) and tetracycline (81.7%) but were however susceptible to ofloxacin (99.3%) and gentamicin (83%). Multiple antibiotics resistance indices (MARI) showed that bacterial isolates from the studied packaged milk samples were multi-resistant with MARI ranging from 0.2 to 1.0. Out of ninety enterobacteriaceae studied, 93.3% of the bacterial isolates had MAR index of 0.3 and above.Conjugation studies revealed that nineteen out of twenty-six.
ANTICONVULSANT AND SUB-CHRONIC TOXICITY STUDIES OF THE METHANOL LEAF EXTRACT OF DIOSPYROS MESPILIFORMIS HOCHST (EBENACEAE) IN LABORATORY ANIMALS
(2014-02) MUHAMMAD, Kasimu
Diospyros mespiliformis hochst (Ebenaceae) known in English as ebony is a plant that is found throughout West Africa. The Plant was reported to have wide ethnomedical application notably in fever, whooping cough, wounds, pneumonia, syphilis, leprosy and epilepsy among others. This study examined the anticonvulsant activity of its methanol leaf extract in mice and day old chicks against pentylenetetrazole, maximal electroshock, strychnine and 4 amino pyridine induced seizure tests. Valproic acid, phenytoin and phenobarbitone respectively were used as reference anticonvulsant drugs for comparison. The sub-chronic toxicity studies was also carried out in rats to determine the effect of twenty eight days p.o.(per oral) administration of the methanol leaf extract of D.mespiliformis on renal and hepatic function parameters followed by histopathological examination. The extract at i.p.(intraperitoneal) doses of 50, 100 and 200mg/kg protected the mice (50%, 66.67% and 66.67%) against pentylenetetrazole induced seizures respectively the mean onset of seizure was however not significantly increased when compared with the negative control at P<0.05. The extract at i.p doses of 250, 500 and 1000 mg/kg did not produced any significant anticonvulsant activity against maximal electroshock induced seizure, similarly, at i.p doses of 50, 100 and 200 mg/kg, the extract also did not show any significant activity against 4-amino pyridine induced seizure even though it showed only 16.67% protection with the 200mg/kg dose. Also no significant activity against strychnine induced seizure even though it significantly (P<0.05) prolonged the onset of seizure induced by strychnine but failed to protect the animals against strychnine induced lethality. The methanol leaf extract of D.mespiliformis causes significant elevation of alkaline phosphatase (ALP) at p.o. doses of 50 mg/kg (P<0.05), 500mg/kg (P<0.05) and 1000 mg/kg (P<0.001), the values of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST), Total bilirubin were however not significantly elevated at p.o doses of 50, 250, 500 and 1000 mg/kg. In the renal function tests, the result showed significantly elevated potassium levels at p.o dose of 250 mg/kg P<0.05 and also significant decrease in creatinine values at p.o. doses of 250, 500 and 1000 mg/kg at P<0.01 respectively. No significant changes in the values of sodium, total calcium, glucose, total cholesterol, urea, total protein and albumin at P<0.05. Histopathological studies on the other hand revealed moderate (with 500 mg/kg p.o dose) to severe (with 1000 mg/kg p.o. dose) degeneration of hepatocytes, hepatocellular necrosis and lose of hepatic architecture with the liver and moderate (with 500 mg/kg p.o. dose) to severe (with 1000 mg/kg p.o dose) loss of renal tubular architecture and degeneration of renal tubules but with intact glomerali with the kidney. The median lethal dose (LD50) values of D.mespiliformis methanol leaf extract were found to be 774.6mg/kg i.p. and >5000 mg/kg p.o. in both rats and mice. While in chicks, the value was found to be >5000 mg/kg intraperitoneally. The preliminary phytochemical screening revealed the presence of alkaloids, saponins, flavonoids, tannins, carbohydrates, cardiac glycosides, and combined anthracene type of anthraquinones. These results suggests that D.mespiliformis leaf extract posses biologically active phytoconstituents that have anticonvulsant activity and are hepatotoxic and nephrotoxic at higher doses
ANTICONVULSANT STUDIES OF THE METHANOL EXTRACT AND FRACTIONS OF CASSIA SIAMEA LAM. (FABACEAE) IN MICE AND CHICKS
(2014-08) BELLO, RAMATU OMENESA
Cassia siamea is a shrub belonging to the Fabaceae family, native of Southeast Asia. The plant is commonly used in traditional medicine to treat hypertension, malaria and diabetes. Due to the easy cultivation of the plant, its widespread and also remarkable biological activities, Cassia siamea has become a worldwide medicine. The study was conducted to assess the anticonvulsant potential of the methanol extract of Cassia siamea (CSME) and its fractions (EAF, NBF and RAF) using Pentylenetetrazole (PTZ) induced seizures in mice and Maximal electroshock (MES) induced seizures in chicks. Acute toxicity was carried out on CSME and fractions. The possible mechanism(s) involved in anticonvulsant action were determined using Picrotoxin and naloxone. The preliminary phytochemical screening of the methanol extract revealed the presence of alkaloids, flavonoids, polyphenols, saponins, steroids, terpenoids and tannins. The LD50 of CSME, its EAF and NBF was found to be greater than 5000mg/kg intraperitoneally (i.p) in chicks and mice, suggesting a non toxic profile of the extractst, while the LD50 of the RAF (i.p) was found to be 1095mg/kg in mice and 3807 mg/kg in chicks implying the RAF is mildly toxic via the intraperitoneal route. The CSME and its EAF were found to have varied anticonvulsant activities; the EAF at 250mg/kg dose protected 40% of mice against hind limb tonic extension induced by maximal electroshock and in convulsed chicks a significant (P < 0.05) decrease in mean recovery time was noted. The ethyl acetate fraction at 250mg/kg and 500mg/kg doses produced a significant (P < 0.05) delay in mean onset of seizures and offered mice a 2/6 and 5/6 quantal protection against mortality, valproic acid the standard anticonvulsant drug used produced a 100% protection against seizures. The EAF did not protect mice against pirotoxin induced seizures indicating lack of activity on chloride ion channels of the GABAA receptor complex. Naloxone did not reverse the anticonvulsant activity of the EAF 2 against Pentylenetetrazole-induced seizures, suggesting lack ogf involvement of GABAA-BDZ receptors and opioid receptors in the anticonvulsant effect of EAF. The CSME and EAF at 100mg/kg dose significantly (P < 0.05) prolonged the total duration of Diazepam induced sleeping time in mice without affecting the mean onset of sleep, indicating sedative action of the extract. The results suggests the presence of bioactive component(s) that posess anticonvulsant and sedative activities. The data may provide pharmacological basis for the use of the plant alone or in combination with other plant(s) in the management of febrile convulsions and insomnia in West African countries including Nigeria
ANTICONVULSANT STUDIES OF THREE SYNTHESIZED DICHLORO-SUBSTITUTED PHENYL PROPANAMIDES AND THEIR ACTION ON VOLTAGE-GATED SODIUM CHANNELS (Nav1.6)
(2015-03) MALAMI, SANI
The field of antiepileptic drug development has become dynamic, affording many promising research opportunities. Continued efforts are being made in the development of antiepileptic drugs employing a range of strategies, including modification of the structures of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening. This research is aimed at conducting anticonvulsant studies on three synthesized dichloro-substituted phenyl propanamides. Isomers of 2,3- (DCP23)- 2,5- (DCP25) and 3,4- (DCP34) Dichloro-substituted Phenyl Propanamides were synthesized from acrylamide and dichloro-substituted anilines. The products were formed by an addition reaction according to Michael’s reaction. The physicochemical properties of the products were determined, and their structures were elucidated using standard analytical procedures; infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy. The test compounds were evaluated for anticonvulsant effect in both acute and chronic animal models, via intraperitoneal (i.p.). In maximal electroshock test (MEST), the percentage protection offered by DCP23, DCP25 and DCP34, at 50 mg/kg, was 71.4%, 57.2% and 42.9% respectively. The middle dose (25 mg/kg) of the compounds offered protection of 42.9% (DCP23), 28.5% (DCP25) and 14.3% (DCP34), while the lowest dose (12.5 mg/kg) offered minimal / no protection. The highest dose (50 mg/kg) of DCP23, DCP25 and DCP34 used in pentylenetetrazole-induced seizure test, offered 66.7%, 66.7 and 0% protections against clonic seizures. Also, DCP23, at doses of 25 and 12.5 mg/kg, produced 16.7% protection while similar doses of DCP25 and DCP34 did not offer any protection. There was statistically significant difference in the mean onset of seizure exhibited by DCP23 at doses of 50 mg/kg (p<0.001) and 25 mg/kg (p<0.001). In 4-aminopyridine-induced seizure test, there was no protection offered by all the tested compounds, but DCP34 at doses of 50 mg/kg and 25 mg/kg viii exhibited statistically (p<0.05) significant difference in the onset of seizures. All test compounds did not offer protection in strychnine-induced seizure test. In Picrotoxin-induced seizure test, DCP23 and DCP25 offered protection against clonic convulsion of 66.7% and 83.3% (50 mg/kg) respectively and 50.0% and 66.7% (25 mg/kg) respectively. There was no protection at 12.5 mg/kg. The medial effective dose (ED50) for DCP23, DCP25 and DCP34 using MEST was found to be 25.12, 39.81 and 44.67 mg/kg respectively, while that of picrotoxin was 35.48 mg/kg (DCP23) and 28.18 mg/kg (DCP25). The median toxic doses (TD50) were 100.0, 100.0 and 104.7 mg/kg for DCP23, DCP25 and DCP34 respectively. The protective index (MEST) was 3.98, 2.51 and 2.33 respectively while that of picrotoxin-induced seizure test was 2.82 (DCP23) and 3.55 (DCP25). In the single oral administration (100 mg/kg) evaluation, DCP23, DCP25 and DCP34 offered 37.5%, 50% and 0.0% protections respectively against tonic hind limb extension (THLE) while a 5-day administration offered higher protection of 50%, 75% and 25% respectively. Co-administration of DCP23 (50 mg/kg), DCP25 (50 mg/kg) and DCP34 (50 mg/kg) each with 5 mg/kg fluphenamic acid, resulted in potentiation as the percentage protection against THLE (MEST) were 100% for DCP23 and DCP25, and 50% for DCP34. When DCP23 and DCP25 at the doses of 25 mg/kg, were coadministered with nickel chloride (5 mg/kg) the percentage protection against PTZ-induced seizure were 66.67% and 33.33% respectively. Similarly, their co-administration produced significant (p<0.05) difference in the mean onset of seizure when compared with the control group. Cyproheptadine at the dose of 4 mg/kg did not affect the anticonvulsant effect of DCP23 (50 mg/kg) and DCP25 (50 mg/kg) against PTZ-induced seizure. DCP23 (50 mg/kg) and DCP25 (50 mg/kg), significantly (p<0.001) decreased the onset of sleep as well as increased the duration of sleep (p<0.05). All the compounds at the dose of 50 mg/kg significantly (p<0.05) reduced the ix severity of seizure episodes induced by kindling. A 28-day sub-chronic study was conducted for DCP25 at doses of 50, 25 and 12.5 mg/kg. The results showed that DCP25 at 50 mg/kg only, caused significant (p<0.05) increase in urea, creatinine and aspartate aminotransferase levels. There was no significant (p<0.05) change in haematological indices, lipid profile parameters as well as other renal and liver function test parameters caused by DCP25. The possible mechanism of action was studied on voltage-gated sodium channels(Nav1.6) at different states of the channel: DCP23 at holding potential of -60 mV, produced concentration-dependent tonic blockade of sodium current of 9.73%, 18.04%, 46.80%, 68.46%, 95.64 and 98.10% at 10μM, 30μM, 60μM, 100μM, 300μM and 600μM respectively. At holding potential of -60 mV, DCP25 at 100μM and 600μM blocked the current by 21.63% and 83.03%; while DCP34 (100μM and 600μM) blocked the current minimally by 3.8% and 16.9%, respectively. DCP23 was further tested at a holding potential of -100 mV at the graded concentration (10μM, 30μM, 60μM, 100μM, 300μM and 600μM) and similarly blocked the sodium currents by 0%, 10%, 28.93%, 50.12%, 88.51% and 90.10% respectively. The IC50 values of DCP23 were 64.76 and 100.37 μM at resting and inactivated states respectively. The activation/inactivation pattern in the presence of DCP23 (100 μM) indicated that there was significant reduction in the elicited current even at depolarized potential where the sodium conductance was found to be highest. The results obtained from this work showed that the compounds possess anticonvulsant effects mediated partly via voltage-gated sodium channel blockade.

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