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.