It is well known that inflammatory stimuli can depress concentrations and activities of hepatic cytochromes P450. This phenomenon has been studied with gram-negative bacterial cell wall endotoxin, but has not yet been reported with gram positive bacterial products. Because critically ill septic patients are more likely to have infections with gram positive organisms (often staph sp.) we decided to see if purified SEB (Toxin Tech, Inc. - 3 mg/kg) would affect P450s in male C3H/HeN mice (25 g) and compared it to endotoxin [lipopolysaccharide (LPS), E. coli 0111:B4-0.5 mg/kg]. Both agents were injected ip and microsomes prepared from mice killed 24h later. Total P450 concentrations were 0.95+/-0.09 nmol/mg protein in saline controls, 0.62+/-0.09 after LPS, and 0.66+/-0.06 after SEB. Paranitro-phenol hydroxylase, a specific activity of P450 2E1, was 74+/-19 pmol/mg/min in saline controls, 28+/-12 after LPS, and 40+/-9 after SEB. (Values are mean +/- SD for 5 mice). We conclude that a gram-positive stimulus like SEB can also depress cytochrome P450 concentrations and at least the activity of the 2El isozyme in mice.
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