Inhibition of mouse liver cytochrome P-450 by gram-negative bacteria lipopolysaccharides.

The ability of bacterial endotoxins, of different origin, to modify the level of mouse liver cytochrome P-450 was investigated. Endotoxins, (lipopolysaccharides, LPSs) were isolated from Proteus, Escherichia, Salmonella, Bacteroides and Coxiella strains. The most potent inhibitor of cytochrome P-450 activity was S. typhi 0101 LPS, which at a dose of 1 microgram/mouse reduced the cytochrome P-450 activity to 59%. E. coli O55:B5, S. typhimurium, P. mirabilis O3, and C. burnetii LPSs, at dose 10 micrograms/mouse, decrease cytochrome P-450 level from 56 to 69%. B. ovatus LPS significantly suppressed the expression of cytochrome P-450 only at the highest dose used-100 micrograms/mouse. The comparison of inhibitory activity of P. mirabilis complete, S and R types of LPSs indicate that lipid A portion of LPSs are sufficient to decrease the cytochrome P-450 level. However, the core oligosaccharide of LPS significantly enhance that inhibition. The isolated O-specific polysaccharide part of P. mirabilis O3 LPS did not decrease cytochrome P-450 level. The comparison of biological activity of Proteus LPSs, tested by chromogenic Limulus amebocyte lysate (LAL) test, demonstrated the enhancement effect of O-polysaccharide part of tested LPSs.