Effect of glutathione and N-acetylcysteine on hepatocellular modifications induced by 2-acetylaminofluorene.
The exposure of rats to a dietary regimen containing 2-acetylaminofluorene induces a sequence of hepatocellular alterations leading to the development of preneoplastic nodules. Groups of 2-acetylaminofluorene-treated rats were given glutathione or N-acetylcysteine to evaluate the effects of these different thiols on the sequence of events that originate transformed cells. It is well known that intracellular thiols protect biological macromolecules from scavenging free radicals and electrophilic compounds produced by the metabolism of chemical agents. Male Wistar rats were maintained on a feeding regimen containing 0.05% 2-acetylaminofluorene. The diet of 2 groups of 2-acetylaminofluorene-treated animals was supplemented with either 0.1% glutathione or N-acetylcysteine. The effects in the liver of the exogenously supplied thiols during 2-acetylaminofluorene treatment were assessed evaluating DNA damage, glutathione levels, activity of marker enzymes glucose-6-phosphatase, gamma-glutamyltranspeptidase, and glutathione-S-transferase, survival rates, and development of salivary gland tumors. Our results demonstrate that the mortality due to 2-acetylaminofluorene exposure was reduced or completely abolished by thiols and that the development of salivary gland tumors was inhibited. Exogenously supplied thiols significantly reduced DNA damage as assessed by alkaline elution. At the doses employed, glutathione and N-acetylcysteine induce early stimulation of glutathione-S-transferase, had little effect on the loss of glucose-6-phosphatase activity and scanty influence on the net increase in gamma-glutamyltranspeptidase activity.
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D004247:DNA / Q000187:drug effects; D004347:Drug Interactions; D005978:Glutathione / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D012468:Salivary Gland Neoplasms / Q000139:chemically induced; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D004247:DNA; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D005978:Glutathione; D000111:Acetylcysteine