BIOCHEMICAL STUDIES ON THE POTENTIAL ROLE OF HYPERTDYROIDISM IN THE BIOACTIVATION OF PARACETAMOL TO INDUCE HEPATIC LESIONS IN EXPERIHENTAL ANIMALS

Abstract

Paracetamol (acetaminophen, N-acetyl-para-aminophenol , APAP; Pando! and many other trade names elsewhere)is a derivative ofpara­ aminophenol (Black, 1980) . It was synthesized at Johns Hopkins University in 1877 (Spooner and Harvey, 1986) and well-described in 1894 (Hinsberg and Treupe1 , 1894) without side-effect in normal

use . Paracetamol is a safe and effective analgesic and anti-pyretic when taken in the usually recommended dose for limited periods of time (Batterman and Grossman, 1955 ; Piperon et al., 1978; Black, 1980; Tee et a/.,1987) but when taken in overdose it produces serious, often irreversible and fatal heptotoxicity, as well as necrosis in other vital organs (Koch-Weser, 1976) in man and experimental animals (Boyd and Bereczky, 1966 ; Davidson and Easthman, 1966 ; Ameer and Greenblatt, 1977;Spooner, 1993). In 1973 there were about 5000 cases of self-poisoning with paracetamol in Britain with 50 deaths. Up to 1976, over 1000 patients with paracetamol overdose were admitted to hospitals in England and Wales every year and about 3% died (Douglas eta!., 1976).

Hepatotoxicity of paracetamol IS preceded by its metabolic biotransformation by cytochrome P450 mixed-function oxidase to reactive intermediate (Jollow et a/., 1973; Mitchell eta!., 1973 a; Potter et a!., 1973; Hinson, 1982 ). Consequently the severity of the