THE AMELIORATIVE EFFECTS OF VITAMINS C AND E ON NEUROTOXIC, HAEMATOLOGIC AND BIOCHEMICAL CHANGES INDUCED BY CHRONIC CHLORPYRIFOS IN ADULT WISTAR RATS
THE AMELIORATIVE EFFECTS OF VITAMINS C AND E ON NEUROTOXIC, HAEMATOLOGIC AND BIOCHEMICAL CHANGES INDUCED BY CHRONIC CHLORPYRIFOS IN ADULT WISTAR RATS
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Date
2009-02
Authors
AMBALI, SULEIMAN FOLORUNSHO
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Abstract
Experiments were performed with the aim of evaluating the effect of chronic exposure to
chlorpyrifos (CPF) on neurotoxieological, clinicopathological, haematologieal and
biochemical changes, and the effect of antioxidant vitamins C and/or E on these changes in
Wistar rats. Fifty adult Wistar rats divided into 5 groups of 10 animals each (5 males and 5
females in each group) served as subjects for this study. Rats in group I were given soya oil
(S/oil) only at a dose of 2ml/kg daily. Rats in group II (CPF only) were exposed to CPF only
at 10.6 mg/kg (l/8th of LD50), while those in group 111 were pretreated with vitamin C at a
dose of 100 mg/kg before exposure to CPF (10.6 mg/kg) (VC+CPF) 30 minutes later. Rats in
group IV were pretreated with vitamin E at a dose of 75 mg/kg before being administered
with CPF (10.6 mg/kg) (VEiCPF) 30 minutes later, while those in group V were pretreated
with a combination of vitamins C+E followed by exposure to CPF (10.6 mg/kg)
(VC+VE+CPF) 30 minutes later. The regimens were orally administered to each animal in
all the groups once daily for 17 weeks. During this period, the rats were examined for clinical
signs, weekly body weight changes and death. The effect of the different regimens on motor
activity, anxiety, habituation learning, sensorimotor reflex, motor strength, learning and
memory were assessed using appropriate ncurobehavioural asessment protocols. At the end
of the study period, the rats in each group were sacrificed for haematologieal, serum
biochemical and tissue pathological examinations. The haematologieal parameters analysed
were packed cell volume (PCV), haemoglobin (lib) concentration, red blood cell (RBC)
count, absolute and differential white blood cell (WBC) count, and in-vitro erthrocyte
osmotic fragility. The scrum biochemical parameters analysed included aspartate
aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AFP),
y-glutamyl transferase (GGT), creatine kinase (CK), Na1, K', CI" and HCO3 Other
parameters evaluated included total proteins albumin, globulin, urea, uric acid, creatinine.
glucose, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4),
triglycerides (TG), cholesterol (TC), high density lipoprotein-cholestcrol (HDL-c) and lowdensity
lipoprotein-cholesterol (LDL-c). Gross examination of tissues and organs were
carried out, while histopathological examinations on sections of the brain, liver, stomach,
intestine, pancreas, kidneys, lungs and spleen were evaluated. In addition, the effect of the
regimen on lipid peroxidation was analysed by evaluating the concentration of thiobarbituric
acid reactive substances (TBARS), malonaldehyde (MDA) in the liver, brain and the serum.
The results showed that rats exposed to CPF only manifested toxic signs, reduce body weight
gain, increased anxiety; caused impairment of motor activity, coordinated gait,
neuromuscular coordination, motor strength, sensorimotor reflex, learning and memory.
Pretreatment with vitamins C and/or E ameliorated the CPF-induccd neurobchavioural and
cognitive changes. Exposure to CPF resulted in reduction in the values of PCV, RBC, Hb
and WBC, uric acid, IP, albumin, CK, TSH, T3, T4,TC, TG and IIDL-c. Exposure to CPF
also caused increased erythrocyte osmotic fragility, globulin, glucose, creatinine, AST, ALT,
AEP, GGT, LDL-c, serum and tissue MDA. No difference in the electrolytes level was
observed in all the groups. Pretreatment with vitamins C and E but not the combination of
both vitamins caused further increase in LDL-c. On the whole, pretreatment with vitamin C
and/or E ameliorated CPF-induced haematological and biochemical changes. Severe
degenerative changes involving neuronal and glial cells of the cerebrum, hepatocytes,
myocardial cells, glomeruli and renal tubules, glandular and non-glandular portion of the
stomach, intestinal villi, submucosal and muscular layer of the intestine; pancreas and spleen
were observed in rats exposed to CPF only. Pretreatment with antioxidant vitamins C and/or
E generally resulted in milder pathological lesions in the organs compared to those exposed
to CPF only. The study has shown that chronic exposure to CPF induces clinicopathological,
neurobchavioural, cognitive, haematological and serum biochemical changes in Wistar rats,
and that pretreatment with antioxidant vitamins C and/or E ameliorated the changes. The
study has further shown that induction of increased lipid per-oxidation by chronic CPF
exposure plays an important role in the molecular mechanisms of these changes.
Description
A DISSERTATION SUBMITTED TO THE
POSTGRADUATE SCHOOL, AHMADU BELLO
UNIVERSITY, ZARIA, NIGERIA
IN PARTIAL FULFILLMENT FOR THE AWARD OF
DOCTOR OF PHILOSOPHY IN VETERINARY
TOXICOLOGY
DEPARTMENT OF VETERINARY PHYSIOLOGY
AND PHARMACOLOGY
AHMADU BELLO UNIVERSITY, ZARIA
NIGERIA
FEBRUARY 2009
Keywords
AMELIORATIVE,, EFFECTS,, VITAMINS C AND E, NEUROTOXIC,, HAEMATOLOGIC,, BIOCHEMICAL,, CHANGES,, INDUCED,, CHRONIC,, CHLORPYRIFOS,, ADULT,, WISTAR,, RATS