COMPARATIVE STUDY ON EFFECTS OF DILTIAZEM VERSUS N-ACETYL CYSTEINE IN ACUTE ACETAMINOPHEN INTOXICATION IN MICE

Abstract

Acetaminophen is one of the most commonly used non narcotic, analgesic antipyretic agents. It has only weak anti-inflammatory activity. Most of the documented acetaminophen poisoning were the result of suicidal attempts. Toxic doses of the drug have been shown to produce acute hepatic necrosis and/or renal failure in man and in experimental animals. Despite considerable research, the mechanism responsible for the acetaminophen induced hepato or nephrotoxicity is unknown. Investigators have postulated that the covalent binding of acetaminophen metabolites to cellular protein may lead to cell toxicity. Also, the disruption of calcium homeostasis has been proposed as a mechanism involved in the pathogenesis ofhepato- and nephrotoxicity. Regarding acetaminophen induced nephrotoxicity, acute renal failure has been reported despite adequate treatment with NAC, the conventional antidote of acetaminophen intoxication. It was suggested that in addition to calcium hypothesis microvascular damage v{a:s an important mechanism for the renal injury after acetaminophen intoxication. The aim of the present work was to evaluate the effect of a new antidote (diltiazem) as compared to the conventional one N­ acetyl cysteine (NAC) on acetaminophen induced hepatotoxicity in mice. Also to study the effect ofN- Acetyl cysteine and diltiazem on the kidney during their use in the treatment of acetaminophen induced toxicity in mice. The present study was carried out on 80 mice of both sexes, their body weight ranged from 25-30 g.