Inhibiting or potentiating effects of flavonoids on carbon tetrachloride-induced toxicity in isolated rat hepatocytes.
Carbon tetrachloride (CCl4) added to isolated rat hepatocytes produces toxic effects which were assessed by monitoring the release of aspartate aminotransferase (ASAT). CBrCl3 was equitoxic with CCl4, while CHCl3 was inactive, suggesting solvent properties not to be involved. The CCl4-mediated toxicity was markedly decreased by carbon monoxide, indicating possible activation by cytochrome P 450. 55 flavonoid compounds were tested for their ability to interfere with CCl4-induced release of ASAT. The compounds are cianidanol, 3-ethers and 3-esters thereof, flavanones, flavanolols, flavones and flavanols. The more hydrophilic compounds inhibit the CCl4-induced toxicity, while the lipophilic derivatives are potentiators. No other structure-activity relationships are apparent. The results are discussed in terms of the mechanisms of action of the compounds and of the validity of the technique as a screening test for hepatotropic agents.
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000503:physiopathology*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000503:physiopathology*; D002725:Chloroform / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D005419:Flavonoids / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship
D005419:Flavonoids; D002725:Chloroform; D003577:Cytochrome P-450 Enzyme System