EVALUATION OF THE IN-VIVO ANTIMALARIAL ACTIVITY OF
EVALUATION OF THE IN-VIVO ANTIMALARIAL ACTIVITY OF
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Date
2015-11
Authors
ATULUKU, VICTOR ATAMODU
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Abstract
Malaria control still remains a challenge in Africa where 45 countries, including Nigeria, are endemic for malaria, and about 588 million people are at risk with an attendant mortality rate of roughly 125 deaths per minute. Using mice model, the study was undertaken to evaluate the antimalarial activity of L-isoleucine Hydroxamatein early and established malaria infection by carring out Peter 4-day suppressive test and Rane’s test respectively. The oral acute toxicity for Isoleucine Hyroxamate using the fixed dose procedure was found to begreater than 2000mg/kg body weight. For the anti-malarial evaluation, all experimental groups except the healthy control group (HC) were intraperitoneallyinnoculated with approximately 1.5×107 million parasitized erythrocytes and grouped as; negative control group (NCPD) which received 0.2 ml/day distilled water, Standard group (SGPC) which received 10mg/kg/day Chloroquine, treatment group that received 50 mg/kg body weight L-Isoleucine hydroxamate (TGPIH 50), treatment group that received 100 mg/kg body weight L-Isoleucine hydroxamate (TGPIH 100) and treatment group that received 200 mg/kg body weight L-Isoleucine hydroxamate (TGPIH 200). The antimalarial activity of L-Isoleucine hydroxamatein early malaria infection showed that the TGPIH200 group recorded an average parasitemia of 20.45±6.05% which was not significantly different (P>0.05) from the SGPC group which recorded 5.8±2.21% nor the NCPD group which recorded 34.96±9.10%. Evaluation ofblood glucose, plasmaprotein, packed cell volume, rectal temperature and Body weight during early malaria infection showed that L-Isoleucinehydroxamate significantlyaffected only the packed cell volume and rectal temperature. Packed cell volume for the NCPD group (19.00±6.60 %)was significantly lower than the TGPIH 50 group (30.52±5.94 %) and the TGPIH 200 group (26.00±3.81%). Similarly, rectal temperature for the NCPD group (34.56±0.50 oC) was significantly lower than the L-Isoleucine hydroxamatetreatment groups; TGPIH 50 (35.90±1.58 oC), TGPIH 100 (35.70±0.93 oC) and TGPIH 200 (35.98±0.18 oC) groups.The HC group (52.00±3.06 %, 37.9±0.34 oC) and the SGPC group (45.80±1.90 %, 38.24± 0.46 oC) recorded significantly higher (p<0.05) packed cell volume and rectal temperature values respectively, when compared to the other groups. The antimalarial activity of L-Isoleucine hydroxamate in established malaria infection was lost on day-4 of the rane’s test. The average parasitemia for the TGPIH 200 group was 18.09±9.02% and was significantly (P<0.05) higher than that of the NCPD group (6.19±1.30 %) and the SGPC group (0.00±0.00%). Thus there was no significant difference (P>0.05) in blood glucose, plasma protein, Packed cell volume, rectal temperature and Body weight, when especially the TGPIH 200 group was compared with the NCPD group. The SGPC group recorded significantly (P<0.05) longer survival time of 28.00±0.00 days compared to the other groups. There was no significant difference (P>0.05) in survival time between the NCPD group (19.60±2.39 days) and the TGPIH group (19.20±3.78 days).These findings show that L-Isoleucine Hydroxamate has antimalarial activity in early malaria infection. However, in established malaria, its antimalarial activity was not sufficient to provide a lasting suppressive action to bring about a curative response.
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A DISSERTATION SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES, AHMADU BELLO UNIVERSITY, ZARIA IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE AWARD OF MASTER DEGREE IN BIOCHEMISTRY DEPARTMENT OF BIOCHEMISTRY, FACULTY OF SCIENCE AHMADU BELLO UNIVERSITY, ZARIA NIGERIA
Keywords
IN-VIVO ANTIMALARIAL, L-ISOLEUCINE HYDROXAMATE