Endotoxic glycolipid as a potent depressor of the hepatic drug-metabolizing enzyme systems in mice.
Inhibitory effects of the endotoxic glycolipid from Salmonella minnesota R595 on hepatic drug-metabolizing enzyme activities in mice were investigated, and the depressor activity of the glycolipid in the enzyme systems was confirmed. Among degradation products of lipopolysaccharides tested, lipid A preparations derived from the mild acetic acid hydrolysates of lipopolysaccharides were the most active, but the lipid A fractions prepared from the hydrolysates with 1 N-HCl were almost inactive. A degraded polysaccharide fraction from E. coli lipopolysaccharide was inactive. The activities of the glycolipid and the lipid A preparation were markedly reduced by treatment with alkaline-hydroxylamine, mild alkali or hydrazine. The data showed that the lipid A moiety of the glycolipid may be responsible for the inhibitory activity on the hepatic drug-metabolizing enzyme systems.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D006017:Glycolipids / Q000494:pharmacology*; D008050:Lipid A / Q000008:administration & dosage; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013997:Time Factors
D004731:Endotoxins; D006017:Glycolipids; D008050:Lipid A; D008070:Lipopolysaccharides; D004364:Pharmaceutical Preparations; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase