CLONAZEPAM INDUCED SUB CHRONIC HEPATORENAL TOXICITY IN RATS AND THE PROTECTIVE ROLE OF ALPHA-TOCOPHEROL

Abstract

Background: Clonazepam (CZP) is an antiepileptic drug approved in 1976 by Food and Drug Administration (FDA) for treatment of various types of seizures, Clonazepam has a high potential for abuse, as well as tolerance, physical dependence, and ultimately addiction. Although many studies confirmed the deleterious effects of other antiepileptic like valproic acid and carbamazepine, those of clonazepam are minimal. Objectives: This research aimed to study and evaluate the hepatotoxic and nephrotoxic effects of sub chronic high dose administration of clonazepam and the protective effect of alpha-tocopherol “vitamin E” (V.E). Methods: Forty (40) healthy male albino rats were included. They were randomly divided into four equal groups (10 rats each): group I (normal saline), group II (CZP misuse), and group III (V.E) and group ΙV (CZP + V.E). All rats received the commenced drugs for 50 days. Serum levels of AST, ALT, ALP, urea, creatinine, and uric acid were measured. Liver and kidney tissues were taken for histopathology. Results: clonazepam in high doses increased hepatic and renal biomarkers levels, disrupted hepatic and renal tissues, and increased the number of degenerated cells. V.E treatment significantly attenuated the deleterious effects induced by clonazepam.