Cytotoxicity of the phytosterol diosgenin and its derivatives in rat cultured hepatocytes and V79 fibroblasts.
In this work, the cytotoxic effects of some spirostane derivatives were examined in cultured hepatocytes and V79 fibroblasts using different viability assays. The derivatives were obtained by modifying the A and B rings of diosgenin. Diosgenin and its derivatives were more toxic in V79 fibroblasts (IC50 40-300 microM) than in hepatocytes (IC50 280-1000 microM). Inhibition of cytochrome P450IIIA in cultured hepatocytes by incubation with 1 mM cimetidine did not alter the toxicity of these compounds in these cells. These observations suggest that other pathways of detoxification may be involved in hepatocytes. In conclusion, the compounds studied merit investigation for their potential pharmacological and industrial applicability.
Melo
Patricia Silva
PS
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), SP. pmelo@unicamp.br
De Azevedo
Mariangela Burgos Martins
MB
Zullo
Marco Antônio Teixeira
MA
Fabrin-Neto
João Batista
JB
Haun
Marcela
M
D000818:Animals; D002452:Cell Count; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000032:analysis; D004144:Diosgenin / Q000031:analogs & derivatives / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009499:Neutral Red / Q000378:metabolism; D051381:Rats; D013778:Tetrazolium Salts / Q000378:metabolism
D004338:Drug Combinations; D013778:Tetrazolium Salts; D009499:Neutral Red; D002927:Cimetidine; D004247:DNA; D004144:Diosgenin