Fatty liver induced by high doses of rifampicin in the rat: possible relation with an inhibition of RNA polymerases in eukariotic cells.
The steatogenic effect on the liver of Rifampicin, a potent inhibitor of the DNA-dependent RNA polymerase in bacteria, was investigated in male and female rats which received either 200 mg or 400 mg of Rifampicin/kg/24 h for 8 days. The determination of total lipids (TL), triglycerides (TG), total cholesterol (TC) and phospholipids (PL) showed a significant increase of TL, TG and TC in the liver at a dose of 400 mg. There was better reproducibility in the male whose blood TG and PL were significantly decreased. These results showed that fatty liver can be induced by very high doses of Rifampicin in rats. A blockage of the very low density lipoproteins (VLDL) biosynthesis and/or secretion can be expected. As a potent steatogenic toxin, alpha-amanitin, is a strong inhibitor of RNA polymerase II in eukariotic cells, a relationship between the RNA polymerase inhibition induced by both of substances and a subsequent inhibition of the biosynthesis of the protein moiety of lipoproteins can be considered. Nevertheless Rifampicin is at present not considered as an inhibitor in eukariotic cells and it will be of great interest to test such a possibility with the high doses used in these experiments, in further work.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D005057:Eukaryotic Cells / Q000201:enzymology; D005234:Fatty Liver / Q000139:chemically induced* / Q000201:enzymology; D005260:Female; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D012293:Rifampin / Q000633:toxicity*
D012321:DNA-Directed RNA Polymerases; D012293:Rifampin