Alteration of precocene II-induced hepatotoxicity by modulation of hepatic glutathione levels.

Abstract

Precocene II (6,7-dimethoxy-2,2-dimethyl-2H-benzo[b]pyran), an insect growth regulator that is structurally related to several naturally occurring carcinogenic and non-carcinogenic alkenylbenzenes, is genotoxic and produces hepatic centrolobular necrosis in rats. This investigation was conducted to evaluate the effects of modulation of hepatic glutathione levels on the toxicity of precocene II. Administration of a toxic dose of precocene II (175 mg/kg) to male Sprague-Dawley rats rapidly depleted hepatic GSH, produced histopathological changes in the liver, and induced increases in serum aminotransferase activity. Concurrent administration of the cysteine pro-drug L-2-oxothiazolidine-4-carboxylic acid (OTC) prevented these toxic effects of precocene II. In contrast, pretreatment of rats with DL-buthionine-SR-sulfoximine (BSO), an inhibitor of glutathione synthesis, potentiated the toxicity of an otherwise non-toxic dose of precocene II (100 mg/kg). These results indicate that glutathione is important for protection from precocene II-induced hepatotoxicity.

• Authors: S K Duddy, M T Hsia
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 71 Issue 2-3 Pg. 187-99 ( 1989) ISSN: 0009-2797 [Print] Ireland
• PMID: 2598296 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzopyrans
• Insecticides
• Thiazoles
• Thiazolidines
• Methionine Sulfoximine
• precocene II
• Buthionine Sulfoximine
• Aspartate Aminotransferases
• Alanine Transaminase
• Glutathione
• Pyrrolidonecarboxylic Acid
• 2-oxothiazolidine-4-carboxylic acid

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Benzopyrans (toxicity)
• Buthionine Sulfoximine
• Glutathione (metabolism)
• Insecticides (toxicity)
• Liver (drug effects, metabolism, pathology)
• Male
• Methionine Sulfoximine (analogs & derivatives, pharmacology)
• Plants
• Pyrrolidonecarboxylic Acid
• Rats
• Rats, Inbred Strains
• Reference Values
• Thiazoles (pharmacology)
• Thiazolidines