Treatment of rats with the peroxisome proliferator ciprofibrate results in increased liver NF-kB activity

Nuclear factor kappaB (NF-kappaB) is an important stress-induced transcription factor in many cell types, including hepatocytes. Previous studies have shown that reactive oxygen species, including hydrogen peroxide, are potent activators of NF-kappaB. Peroxisome proliferators are a group of rodent chemical carcinogens that have been proposed to act by increasing reactive oxygen in the liver. These results led us to consider whether peroxisome proliferators would increase NF-kappaB activity in the liver. Here we demonstrate that rats fed diets containing the peroxisome proliferator ciprofibrate exhibit increased hepatic NF-kappaB DNA-binding activity. This observation suggests that NF-kappaB may contribute, in part, to peroxisome proliferator-mediated changes in the liver.