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Protective effect of diethylmaleate pretreatment on carbon tetrachloride hepatotoxicity

1981; Elsevier BV; Volume: 57; Issue: 3 Linguagem: Inglês

10.1016/0041-008x(81)90232-5

1096-0333

Kenneth A. Suarez, Kathryn A. Griffin, R.P. Kopplin, P Bhonsle,

Drug Transport and Resistance Mechanisms

The administration of diethylmaleate (DEM) to fed and fasted rats produced a marked depletion of hepatic reduced glutathione (GSH) to 26 and 20% of respective saline control values 30 min after drug administration. When carbon tetrachloride (CCl4) was administered to fasted animals pretreated with saline or DEM, the serum enzymes GOT, GPT, and ICDH were elevated 24 hr after intoxication, but the increases were greater in the saline-pretreated group (p < 0.05). The administration of CCl4 to fed animals produced elevations in serum GOT, GPT, and ICDH 24 hr after intoxication that were of similar magnitude in the saline- and DEM-pretreated groups (p > 0.05). CCl4 administration to fed rats produced altered hepatocellular architecture that was of similar magnitude in saline- and DEM-pretreated animals. However, in fasted animals, the histological changes following CCl4 administration were more severe in saline-pretreated animals when compared to the DEM-pretreated group. The data suggest that DEM pretreatment exerts a protective effect against CCl4-induced hepatic injury in fasted rats that may be related to the ability of DEM to inhibit hepatic microsomal drug metabolism.