Acute moderate hypoxia in conscious rabbits: effect on hepatic cytochrome P450 and on reactive oxygen species.

Abstract

This study aimed to document whether acute moderate hypoxia modifies the amount and activity of hepatic cytochrome P450 and in addition, induces changes in the production or the ability to neutralize oxygen reactive species (ORS). Rabbits were exposed to a low partial pressure of oxygen (12%) for 8 or 24 h, killed, and the amount and activity of cytochrome P450, lipid peroxidation, microsomal chemiluminescence and enzymatic scavenger activity were assessed in the liver. After 8 h of hypoxia, total amount but not the activity of cytochrome P450 was decreased, although after 24 h of hypoxia, both the amount and the activity of cytochrome P450 were decreased. Hypoxia for 8 h increased the activity of glutathione peroxidase. However, after 24 h of hypoxia, lipid peroxidation, microsomal chemiluminescence and superoxide dismutase activity were increased, while hepatic glutathione and glutathione peroxidase activity were reduced, modifications that suggest an enhanced presence of ORS. In in-vitro studies, an ORS generating system reduced the activity of cytochrome P450 and enhanced lipid peroxidation of hepatic microsomal membranes, supporting the view that ORS can impair cytochrome P450. The results of the present study show that hypoxia induces changes in the amount and activity of cytochrome P450, as well as in the production or the ability to neutralize ORS, and that these changes are time-dependent.