Abstract

Acetaminophen is a safe analgesic and an antipyretic agent that is available without a prescription. However, high doses of acetaminophen are a direct cause of hepatic toxicity, neurotoxicity, and even death through induction of oxidative stress. The study aimed to evaluate the possible prophylactic and therapeutic effects of nicotinamide (500 mg/kg B.W.) on the behavioral changes examined by forced swim test and open field test, as well as on the antioxidants status in the brain of male Wistar rats that were intoxicated with a single overdose of acetaminophen (5 g/kg B.W.). Acetaminophen showed depressant like behavior, impaired locomotor activity, induced oxidative damage and neurotoxicity through elevation of lipid peroxidation level, reduction of glutathione level, glutathione peroxidase and catalase activities. On the other hand, nicotinamide showed an obvious antidepressant-like effect in the forced swim test in the acetaminophen-intoxicated rats and treated with nicotinamide either in prophylactic or therapeutic ways. However, nicotinamide increased motor deficits and impaired antioxidants status. Neurohistology of the cerebellum showed neuropil vacuolation, and degenerating Purkinje cells with pyknotic nuclei in groups treated with acetaminophen, nicotinamide or both together. In conclusion, caution must be taken upon administration of overdoses of nicotinamide due to its potential neurotoxicity, particularly, upon combination with acetaminophen therapy.

Key words: Acetaminophen; nicotinamide; forced swim test; open field test; oxidative stress; neurotoxicity.