Effects of allopurinol, (+)-cyanidanol-3 and dihydroquinoline-type antioxidants on rat hepatic microsomal cytochrome P-450 and monooxygenases.

The cytochrome P-450 system is a sensitive indicator in different forms of experimental liver diseases in the rat. Both CCl4 and ethanol produce a liver damage by free radical mechanisms causing a lesion of liver cell endoplasmic reticulum. Protective effects of antioxidants on CCl4 or ethanol induced liver damage were investigated on this basis in adult Wistar rats. The strongest protective effect in CCl4 treated animals was shown to be exerted by allopurinol. The other three antioxidants (cyanidanol, MTDQ monomer and MTDQ dimer) could not prevent the CCl4 induced changes, measured by liver/body mass quotient, P-450 concentration, ethylmorphine N-demethylation and ethoxycoumarin O-deethylation. Ethanol in the given doses did not produce any distinct effect on the test parameters. The most sensitive parameter was the ethylmorphine N-demethylation. In conclusion CCl4 intoxication is a suitable model for studying radical initiated liver injuries. The mechanisms of the hepatoprotective effects of the four substances are different.