Xenobiotic tolerance of primary cultured hepatocytes in rats fed a high-fat or high-protein diet.
The diet and nutritional status dominate a tolerance to environmental xenobiotics. In this study, the cytotoxic action of carbon tetrachloride (CCl4) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), one of the dietary carcinogens, was investigated using primary cultured hepatocytes from rats fed a high-fat (23% corn oil) or high-protein (50% casein) diet for three weeks. Both chemicals showed strong cytotoxicity to hepatocytes, which was judged by measurement with the MTT-test and lactate dehydrogenase leakage test. A dietary effect on cytotoxicity was observed; hepatocytes from rats fed the high-protein diet were more susceptible to cytotoxicity than the cells from rats fed a standard diet. On the other hand, ureogenesis, as a cellular function of hepatocytes, was markedly decreased in the cells from rats fed the high-fat diet. These activities were affected in the CCl4-treated cells but not in the Trp-P-1-treated cells. The same trend of both diet and chemical effects was observed in gluconeogenesis from fructose. We conclude that the hepatocytes from rats fed a high-protein diet have high susceptibility to the cytotoxicity of CCl4 and Trp-P-1, but cytotoxicity was not related to the reduction of cellular functions.
Ashida
H
H
Department of Biofunctional Chemistry, Faculty of Agriculture, Kobe University, Japan.
Nakai
R
R
Kanazawa
K
K
Danno
G
G
D000818:Animals; D002243:Carbolines / Q000633:toxicity; D002251:Carbon Tetrachloride / Q000633:toxicity; D002273:Carcinogens; D002470:Cell Survival; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D004044:Dietary Proteins / Q000008:administration & dosage*; D004361:Drug Tolerance; D005943:Gluconeogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009752:Nutritional Status; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism; D015262:Xenobiotics / Q000633:toxicity*
D002243:Carbolines; D002273:Carcinogens; D004041:Dietary Fats; D004044:Dietary Proteins; D015262:Xenobiotics; D014508:Urea; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole