Differential response of primary cultures of human and rat hepatocytes to aflatoxin B1-induced cytotoxicity and protection by the hepatoprotective agent (+)-cyanidanol-3.
The acute hepatotoxicity induced by aflatoxin B1 (AFB1) and the potential protective effect of (+)-cyanidanol-3 (Catergen) were evaluated in both human and rat hepatocytes in primary cultures. AFB1-induced acute toxicity was visualized by light microscope observation and quantified by measurement of lactic dehydrogenase activity in the medium. Human hepatocytes were susceptible to AFB1-induced cytotoxicity but no evident relationship between the concentration of mycotoxin and the extent of cellular damage was established. (+)-Cyanidanol-3 was not toxic at concentrations up to 2 x 10(-3)M, but no obvious protective effect from AFB1-induced injury was evidenced in human cells. By contrast, rat hepatocytes responded in a dose-related manner to AFB1. (+)-Cyanidanol was toxic at 10(-3)M, but even at this concentration exerted a strong protective effect against AFB1-induced cytotoxicity. Such species differences suggest the existence of metabolic differences in both AFB1 and (+)-cyanidanol-3 activating and deactivating mechanisms.
Bégué
J M
JM
Unité de Recherches Hépatologiques U 49, INSERM, Hôpital de Pontchaillou, Rennes, France.
Baffet
G
G
Campion
J P
JP
Guillouzo
A
A
D000293:Adolescent; D000328:Adult; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D002392:Catechin / Q000494:pharmacology*; D002478:Cells, Cultured; D003603:Cytotoxins; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats
D000348:Aflatoxins; D003603:Cytotoxins; D002392:Catechin; D016604:Aflatoxin B1