The hepatotoxic action of chloroform: short-time dynamics of biochemical alterations and dose-effect relationships.

Abstract

Chloroform was administered ip to Balb/c mice as a single dose ranging from 1/8 to 1 of the approximate lethal dose. At different time periods after administration, mice were sacrificed. Serum glutamate-pyruvate transaminase (SGPT) and sorbitol dehydrogenase (SDH) as well as glutathione (GSH) and malondialdehyde (MDA) levels in the liver were determined. Increased SGPT and SDH levels were found for all doses exceeding 1/8 of the approximate lethal dose. The depletion of GSH level was kept within 40% for all doses. A 2-4 fold increase of hepatic MDA level was found. The depletion of hepatic GSH and, to some extent the increase of serum SGPT and SDH, occurred in biphasic fashion. Dose-effect functions for these biochemical alterations could only be constructed for the second, delayed phase of action. It is postulated that the hepatotoxicity of chloroform is mainly dependent on radical formation in the course of biotransformation.