[A selective decrease in cytochrome P450 in the liver microsomes of male rats following phenobarbital and...

The liver microsomal content of cyt. P450 and b5 and activities of selected mixed-function oxidases were compared following phenobarbital (PB)- and 3-methylcholantrene (MC) induction and acute intoxication with carbontetrachloride (CT). PB increased the content of P450 and the activities of both NADPH-cytochrome c reductase and benzphetamin demethylase. MC increased only the content of cytochrome b5. CT after 4 hours damaged selectively the liver monoxidase components: 1. the activity of NADPH-cytochrome c reductase and the content of b5 were not changed in the three groups; 2. the content of P450 was decreased differently: more sensitive to the destructive effect of CT was the PB-inducible P450. Most resistant was the MC-inducible P450; 3. MC decreased the benzphetamin demethylation in control- and PB-microsomes in lower degree than the content of P450. The relative high rates of the benzphetamin demethylase after CT by PB-microsomes was explained by increased activity of NADPH-cytochrome c reductase in this group. The selective damaging effect of CT on P450 was interpreted by complex of local factors: metabolizing of CT to CCL3, lipid peroxidation, phospholipid microenvironment, pO2, antioxidants concentration, activity of heme degrading enzymes.