The use of primary hepatocyte cultures for the evaluation of chemoprotective agents.
Primary cultures of human and rat hepatocytes are widely used in pharmacotoxicological research. This model presents the advantages of retaining liver function for at least a few days, expressing both phase 1 and phase 2 enzymes, and responding to inducers. Recently we made use of primary hepatocytes to investigate the effects of chemoprotective agents on drug-metabolizing enzyme expression and activities. The treatment of rat and human hepatocytes with two chemoprotective agents, oltipraz (a synthetic derivative of 1,2-dithiole-3-thione) and sulforaphane (an isothiocyanate found in broccoli), clearly demonstrated that both of these compounds are inducers of glutathione transferases and transient inhibitors of cytochrome P450, suggesting that these two compounds could exert their chemoprotective effects by both reducing the formation of reactive metabolites of chemicals and enhancing their inactivation.
Morel
F
F
INSERM U 456, Unité Détoxication et Réparation Tissulaire, Université de Rennes 1, Faculté de Pharmacie, France.
Langouët
S
S
Mahéo
K
K
Guillouzo
A
A
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D015197:Carcinogenicity Tests; D002478:Cells, Cultured; D006801:Humans; D017879:Isothiocyanates; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology; D013871:Thiones; D013876:Thiophenes; D018675:Toxicity Tests
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D011719:Pyrazines; D013454:Sulfoxides; D013861:Thiocyanates; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz; C016766:sulforaphane