Withdrawal Effects on Antioxidative and Histochemical Deficits in Acetaminophen Induced Neurotoxicity in Cerebellar Cortex of Adult Wistar Rats

Abstract

Introduction: Neurotoxicity refers to the harmful effects of chemical, biological, or physical agents on the nervous system. Acetaminophen, a common pain reliever whose abuse has been linked to neurotoxicity at high doses, causing oxidative stress and neuronal damage. Aim: The present study aimed to assess the withdrawal effects of Acetaminophen use on the Cerebellar cortex of adult wistar rats. Methodology: Thirty (30) Adult wistar rats weighing 200±50g were assigned into three groups (n=10) of Control (C), Treatment 1(T1) and Treatment 2 (T2). The control group C received distilled water, while Treatment groups T1 and T2 received 200mg/kg of acetaminophen for 4 weeks. However, treatment group T2 were allowed a 2-week acetaminophen withdrawal period. At the end of exposure, all animals were sacrificed via cervical dislocation and eventual removal of cerebellar specimens which were processed for some Neurohistochemical staining reactions as well as Biochemical Quantifications of LDH enzyme and Antioxidative stress markers (SOD & CAT). Quantitative analyses of all data obtained including Body weight, brain weight and Cerebellum weight were analysed using GraphPad® (version 8) and plotted using ANOVA followed by Tukey's multiple comparisons test. Significance was set at p<0.05* (95% confidence interval). Result: Results showed a significant increase in body weight (P=.05) and a decrease in cerebellum weight (P=.01) in both acetaminophen groups. SOD and CAT activity decreased significantly (P=.01) in the T1 groups while T2 groups shows a significant increase, LDH activities decreased significantly (P=.01) in both groups. The Neurohistochemical findings showed severe degeneration, loss of the Purkinje neurons and poorly differentiated DNA on the T1 group compared to control group C while the withdrawal group showed onset of regenerative changes in neurons improved differentiation in DNA stained. Conclusion: The study's findings suggest that long-term acetaminophen use can lead to neurotoxic effects on the cerebellum, but partial recovery is possible upon withdrawal.