Protection from paraquat-induced lung damage and lethality in adult rats pretreated with clofibrate

Abstract

Pretreatment of adult rats with the hypolipidemic agent clofibrate (60 mg/kg/day × 6 days) resulted in a marked degree of protection from paraquat-induced lung toxicity and lethality. The 10-day survival of treated rats was 39 56 (70%) compared to 21 76 (28%) (LT 50 = 2.8 days) for controls ( p < 0.001). Although clofibrate reportedly increases catalase activity in the liver, we found no increases in any of the antioxidant enzymes in the lung (catalase, superoxide dismutase, glutathione peroxidase, or G-6-PD) after clofibrate pretreatment. Lung lipid peroxidation at 24 and 48 hr post-paraquat was equivalent in both groups, although the clofibrate-pretreated rats showed significantly reduced lung edema and pathologic changes at these times. Blood paraquat levels were similar in both groups at 1, 3, and 24 hr postinjection. In two experiments, administration of clofibrate after paraquat injection afforded no protective effects. However, since pretreatment with clofibrate provided the best overall survival rate reported to date after a lethal dose of paraquat (35 mg/kg), further studies toward elucidating the mechanism(s) of action of this agent are warranted. Unraveling the protective mechanism(s) of the pretreatment regimen may still provide valuable clues to suggest effective post paraquat treatment approaches.