Archivum Immunologiae et Therapiae Experimentalis, 1996, 44, 39

Inhibition of Mouse Liver Cytochrome P-450 by Gram-Negative Bacteria Lipopolysaccharides


Abstract. 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 lm g/mouse reduced the cytochrome P-450 activity to 59%. E. coli 055: B5, S. typhimurium, P. mirabilis 03, and C. burnetii LPSs, at dose 10 m g/mouse, decrease cytochrome P-450 level from 56 to 69%. B. ouatus LPS significantly suppressed the expression of cytochrome P-450 only at the highest dose used - 100 m g/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 03 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.

Keywords: Proteus lipopolysaccharides; mouse cytochrome P-450; non-enterobacterial endotoxin.