PMID: 109346Aug 1, 1979

Effect of fasting on metabolite-mediated hepatotoxicity in the rat

Dominique PessayreJ P Benhamou


Acetaminophen and bromobenzene are transformed in the liver into chemically reactive metabolites that may either bind to glutathione and be detoxified or bind to hepatic proteins and produce liver cell necrosis. Fasting for 42 hr (a) decreased hepatic glutathione concentration, (b) increased the amount of chemically reactive metabolite irreversibly bound to hepatic proteins after administration of 3H-acetaminophen or 14C-bromobenzene, and (c) increased the hepatotoxicity of acetaminophen or bromobenzene. In rats fasted for various lengths of time, there was an inverse relationship between the concentration of glutathione in the liver and the activity of serum glutamic pyruvic transaminases after administration of acetaminophen or bromobenzene. In vitro, there was an inverse relationship between the concentration of glutathione in the incubate and the amount of chemically reactive metabolite bound to microsomal proteins after incubation of 3H-acetaminophen or 14C-bromobenzene with hepatic microsomes. It is concluded that fasting may decrease the inactivation of chemically reactive metabolites by glutathione, increase their binding to hepatic proteins, and enhance the hepatotoxicity of drugs transformed into chemically reactive m...Continue Reading

Related Concepts

SGPT - Glutamate pyruvate transaminase
Metabolic Biotransformation
Carbon Radioisotopes
Cytochrome P-450 Oxygenase
Enzyme Induction

Related Feeds

Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. Discover the latest research on atopic dermatitis here.

Related Papers

Canadian Journal of Physiology and Pharmacology
R M WalkerW J Racz
Proceedings of the National Academy of Sciences of the United States of America
B B BrodieJ R Gillette
© 2021 Meta ULC. All rights reserved