PREVENTIVE EFFECT OF FISETIN ON NEUROBEHAVIOURAL, OXIDATIVE STRESS AND HISTOPATHOLOGICAL CHANGES INDUCED BY SUBCHRONIC EXPOSURE TO CHLORPYRIFOS IN MALE ALBINO MICE

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PREVENTIVE EFFECT OF FISETIN ON NEUROBEHAVIOURAL, OXIDATIVE STRESS AND HISTOPATHOLOGICAL CHANGES INDUCED BY SUBCHRONIC EXPOSURE TO CHLORPYRIFOS IN MALE ALBINO MICE

Abstract

Chlorpyrifos (CPF) is one of the common neurotoxicants in Nigeria and the world. Fisetin as an antioxidant (3,3′,4′,7tetrahydroxyflavone) has been used to ameliorate deleterious effects of various neurotoxicants. The aim of the study was to evaluate the preventive effect of fisetin on neurobehavioural, histopathological and oxidative damages, induced by sub-chronic exposure of male mice to CPF. The mice were acclimatised for two weeks and grouped into six groups. Group 1 mice were exposed to distilled water, group 2 was exposed to soya oil at 2 ml/kg, group 3 was exposed to 1% dimethyl sulphoxide at 5 mg/kg, group 4 was exposed to CPF at 6.6 mg/kg, group 5 was administered fisetin at 15 mg/kg, while group 6 was administered fisetin at 15 mg/kg followed by CPF at 6.6 mg/kg 30 minutes later. The mice were administered with this regimen once daily by oral gavage for fifty days, after which they were sacrificed and the organs and tissues harvested for further studies. The neurobehavioural evaluations were carried out on day 0, weeks 3 and 6. Open-field assessment was done using the open-field apparatus, neuromuscular coordination was evaluated using inclined plane and locomotor efficiency was evaluated using ladder walk. The determination of motor strength was done using the forepaw grip time, while excitability score was assessed using the ordinal scale excitability scores. Depression was also evaluated using the forced swimming test and learning and short-term memory was assessed using the step-down inhibitory avoidance task apparatus. The brain sample from each group was used to evaluate CPF-induced histopathological and lipoperoxidative changes, through determination of brain malondialdehyde concentration. The brain was also used to assess activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), using their appropriate kits. The result showed that fisetin significantly (P < 0.05) prevented CPF induced impairments in neuromuscular coordination (67.08 ± 1.24°) and locomotor efficiency (4.42 ± 0.64). It also significantly (P < 0.05) ameliorated CPF effect on brain lipoperoxidative damages MDA (173.90 ± 18.77 nmol/mg protein), activities of antioxidant enzymes, CAT (78.55 ± 7.37 μ/mg protein), GPx (73.96 ± 4.97 mol/min/mL), SOD (143.00 ± 11.09 μ/mL) and acetylcholinesterase activity (11.60 ± 0.55 nmol/min/mL). Fisetin significantly (P < 0.05) mitigated the toxic effects of CPF on the serum lipid profiles of low density lipoprotein (1.14 ± 0.31 mg/gL), high density lipoprotein (0.75 ±0.13 mg/gL), total cholesterol (2.10 ± 0.34 mg/gL) and serum triglycerides (1.10 ± 0.25 mg/gL). It was concluded that fisetin prevented the sub-chronic CPF-induced toxic effects on neurobehavioural, histopathological and oxidative damages in adult male Albino mice.

 

PREVENTIVE EFFECT OF FISETIN ON NEUROBEHAVIOURAL, OXIDATIVE STRESS AND HISTOPATHOLOGICAL CHANGES INDUCED BY SUBCHRONIC EXPOSURE TO CHLORPYRIFOS IN MALE ALBINO MICE

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