Protective effect of flavonoids on drug-induced hepatotoxicity in vitro.
Primary cell cultures of neonatal hepatocytes were used to examine the protective effect of flavonoids in the presence of hepatotoxins. Catechin (CAT) and silybin (SIL) protected the hepatocytes against cell injury produced by erythromycin estolate (EE), amitriptyline (AT), nortriptyline (NT), and tert-butylhydroperoxide (TBOOH). Leakage of lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as morphological parameters, were used as indices of hepatotoxicity. Hepatocytes were exposed to EE (1 X 10(-4) M and 2 X 10(-4) M), AT, NT, and TBOOH (1 X 10(-4) M and 1 X 10(-3) M) for a 2-h period. These hepatotoxins caused significant LDH, AST, and ALT leakage (P less than 0.05) when compared to untreated control groups. NT was less toxic than its parent compound, AT. Changes in morphology were evident after 1 h of treatment with the toxicants, including: vacuole formation, size deformation and cell necrosis. As the concentration of hepatotoxins was increased, the changes were more pronounced. Pretreatment of the cultures with either CAT or SIL resulted in less enzyme leakage and morphological alterations by the hepatotoxins. The results of this study suggest that CAT and SIL may act by stabilizing the plasma membrane against toxic insult.
Davila
J C
JC
Department of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin 78712.
Lenherr
A
A
Acosta
D
D
D000410:Alanine Transaminase / Q000032:analysis; D000639:Amitriptyline / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001219:Aspartate Aminotransferases / Q000032:analysis; D002392:Catechin / Q000494:pharmacology*; D002478:Cells, Cultured; D004918:Erythromycin Estolate / Q000633:toxicity; D005419:Flavonoids / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009661:Nortriptyline / Q000633:toxicity; D010545:Peroxides / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012838:Silymarin / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide
D005419:Flavonoids; D010545:Peroxides; D012838:Silymarin; D000639:Amitriptyline; D002392:Catechin; D020122:tert-Butylhydroperoxide; D009661:Nortriptyline; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D004918:Erythromycin Estolate