Inflammation-induced decrease in hepatic cytochrome P450 in conscious rabbits is accompanied by an increase in hepatic oxidative stress

Abstract

It has been documented that cytokines can induce the formation of reactive oxygen species (ROS) in the liver, and that an inflammatory reaction can locally increase the production of ROS, but it remains unknown whether in vivo a subcutaneous (s.c.) inflammatory reaction can induce the formation of ROS in the liver. To determine in vivo whether an inflammatory reaction, able to decrease the amount of hepatic cytochrome P450, enhances the presence of ROS in the liver, turpentine was injected s.c. to rabbits, which were sacrificed 48 hours later. Control rabbits received saline s.c. The amount and activity of cytochrome P450, as well as several parameters reflecting the presence of ROS were assessed in the liver. Total amount of cytochrome P450 was reduced, as was its activity, assessed by the rates of hydroxylation of aniline and of demethylation of aminopyrine. Moreover, lipid peroxidation increased, while the activity of the enzymatic scavengers, i.e. catalase, glutathione peroxidase and superoxide dismutase decreased. In addition, hepatic concentrations of reduced glutathione were diminished. On the other hand, the activity of the xanthine oxidase system was enhanced by almost 200%. These results strongly suggest an increased presence of ROS. The changes in the amount of cytochrome P450 were inversely correlated with lipid peroxidation. In conclusion, these results show that in vivo an inflammatory reaction, that reduces total cytochrome P450 and its activity, produces simultaneously an oxidative stress in the liver.