MODULATORY ROLE OF VITAMINS A AND E ON LEARNING, MEMORY, MOTOR STRENGTH AND COORDINATION OF CYANIDE INDUCED NEUROTOXICITY IN ALBINO MICE

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Department of Medicine

ABSTRACT
To evaluate effect of sublethal administration of KCN on motor functions, visuo-spatial learning and memory. Some biochemical parameters which include brain malondialdehyde concentration, superoxide dismutase, catalase and acetylcholinesterase activities in adult swiss albino mice and possible ameliorative roles of vitamins A and E. Methods: Thirty five adult swiss albino mice weighing between 18-22g were used. In each group served as subjects for this study. An acute toxicity study was carried out and LD50 was calculated as 15mg/kg. The animals were randomly divided into five groups (n = 7) and exposed to sublethal concentration of potassium cyanide (10% LD50; 1.5 mg/kg). The groupings were as follows; group I (control received 10 ml deionised water), group II (1.5mg/kg KCN), group III (1.5mg/kg KCN + 25mg/kg vitamin A), group IV (1.5mg/kg KCN + 50mg/kg vitamin E) and group V (1.5mg/kg KCN + 25mg/kg vitamin A + 50mg/kg). The animals were fed for 28 days during which neurobehavioral tests using different paradigms was carried out prior to sacrifice and isolation of tissues for biochemical assays. During the study period, Mice were examined for signs of toxicity. Results: From the results obtained from this study, it suggests that motor strength was considerably reduced in the KCN treated group as compared to the vitamins groups. Group2 displayed hypolocomotion on the stationary beam in week 4 (15.8±0.58) while group III recorded decrease in transfer latencies to traverse the beam in week 4 (3.20±0.58). In acquisition and retention, using EPM, group II recorded an increase in transfer latencies (50.40±1.72) and (57.60±0.93) as compared to group IV (29.40±0.68; 5.60±0.60), mice spent more time in the open arms than in the closed arms. Increase in MDA concentration induced by KCN (3.35±0.19) which is an index of lipid peroxidation was mitigated when administered with vitamins A and E (1.82±0.21). Brain SOD activity was significantly (p<0.05) decreased in group2 (1.30±0.27) as compared to group V (2.78±0.10). Brain acetylcholinesterase activity as a biomarker in cyanide toxicity was increased in group II (32.10±0.90) as compared to group III (14.80±0.86). Conclusion:the study suggests that motor deficits and cognitive impairments were correlated with cyanide induced neurotoxicity with increased MDA concentration levels and decreased antioxidant enzymes while the ameliorative effects of vitamins A and E may be due to the inhibition of free radicals overproduction and maintenance of antioxidant defence mechanisms.