Biochemical mechanisms involved in the hepatotoxicity of some drugs.

To find out the biochemical mechanisms involved in the hepatotoxicity of certain drugs, the continuous evolution of some related biochemical parameters was investigated. The results obtained showed the decrease of cytochrome P450, glutathione (GSH) and aniline hydroxylase, as well as increases of lipid peroxides and tryptophan oxygenase 2 hours after i.p. administration of carbon tetrachloride (CCl4) and paracetamol. Characteristic changes of hepatotoxicity such as increase of blood glutamate-pyruvate transaminase (GPT) and triglycerides, and decrease of free sulfhydryl (SH) groups were observed 24 hours after drug administration. The peroxidation of microsomal lipids appears to be the biochemical mechanism involved in the acute administration of these drugs. Subsequently this peroxidation leads to morphologic hepatic changes. In our experimental conditions, hepatotoxicity was prevented by concomitant administration of cystamine.