Add time:09/03/2019         Source:sciencedirect.com

The hepatotoxicity of the 3 isomers of para-substituted thiobenzamides and the 3 isomers of 2-(para-substituted phenyl)-4-methylthiazoles was evaluated in mice depleted of glutathione (GSH) by pretreatment with buthionine sulfoximine (BSO). In accordance with previous studies with the rat, p-methoxythiobenzamide was more toxic than thiobenzamide, and conversely p-chlorothiobenzamide was markedly less toxic as assessed by serum alanine aminotransferase (ALT) activity. The hepatotoxicity of 2-phenyl-4-methylthiazole was also altered by the addition of para-substituents to the phenyl ring in the same way as observed for thiobenzamide derivatives: the rank order of toxicity was 4-methylthiazoles having p-methoxyphenyl > phenyl ⪢ p-chlorophenyl at the 2-position. This good correlation of the rank order of hepatotoxicity between series of 2-(para-substituted phenyl)-4-methylthiazoles and para-substituted thiobenzamides supports the concept that thiobenzamides as ring cleavage metabolites play a role in the hepatotoxicity of 2-phenylthiazole derivatives.

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