Effect of pretreatment with antiinflammatory agents on paraquat toxicity in the rat.

Aspirin (ASA), indomethacin (IND), hydrocortisone (HYC) or 0.25% agar (control) were administered (p.o.) daily to rats for 5 days. Following drug pretreatments, the activities of cytosolic superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR) were elevated 30-70%, 5-25% and 8-25%, respectively. In a second experiment, rats pretreated as above were injected (ip) on the 5th day with paraquat (PQ) (29 mg/kg). Rats in each group expired more ethane 2 hours after PQ injection. After 22 hours, expired ethane returned to zero time levels. All control rats died within 48 hours after PQ injection. At the end of 48 hours, rats pretreated with ASA, IND, or HYC demonstrated survival rates of 13%, 31%, and 47%, respectively. PQ injection produces marked elevations of SOD (82%), GP (328%), and GR (36%) in the lungs of PQ-injected controls rats over non-PQ injected controls. Elevation of these enzymes were also noted in drug-treated rats after PQ injection but at values less than PQ-injected controls. Anti-inflammatory drugs were tested in rat liver homogenates for their ability to inhibit thiobarbituric acid (TBA) reactive product formation. Only the addition of HYC resulted in a decrease formation of TBA-reactive products. Thus in vitro studies suggest that the antiinflammatory drugs tested, other than HYC, may have other mechanisms of actions in addition to inhibition of lipid peroxides.