ABSTRACT
BACKGROUND AND OBJECTIVE: EUK-134 is one of the most promising of the superoxide dismutase (SOD)/catalase mimetic compounds. The antioxidant effects of EUK-134 were tested in a rat model of paraquat pneumotoxicity. METHODS: Male Wistar rats (n = 72) were divided into three groups: group 1, controls; group 2, paraquat alone; group 3, paraquat + EUK-134. Paraquat dichloride was administered per os at a dose of 80 mg/kg. EUK-134 was injected intraperitoneally at 10 mg/kg 2 h before the paraquat and again 4 h later at 5 mg/kg. RESULTS: On days 1, 3 and 5 after treatment with paraquat alone the LDH activity increased (P = 0.0001, P = 0.00001 and P = 0.03, respectively), and the total protein content increased (P = 0.00002, P = 0.001 and P = 0.01, respectively). The levels of acid phosphatase (AcP) in BAL fluid increased on days 1 and 3 (P = 0.006 and P = 0.04). In lung homogenates paraquat alone increased SOD activity on day 1 and decreased it on days 3 and 5. Combined treatment with paraquat and EUK-134 elevated LDH activity on day 3 (significantly less than paraquat alone) and day 5, elevated the total protein content on day 5 only, and did not change AcP activity. The combination of both agents did not alter SOD activity and decreased catalase activity on day 5 significantly less than treatment with paraquat alone (P = 0.05). CONCLUSIONS: EUK-134, a superoxide dismutase/catalase mimetic compound decreased the pneumotoxic effect of paraquat in rats.
Subject(s)
Antioxidants/pharmacology , Herbicides/pharmacology , Lung/drug effects , Organometallic Compounds/pharmacology , Oxidative Stress/drug effects , Paraquat/pharmacology , Salicylates/pharmacology , Animals , Bronchoalveolar Lavage Fluid/chemistry , Catalase , Disease Models, Animal , Lung/metabolism , Lung/pathology , Male , Rats , Rats, Wistar , Superoxide DismutaseABSTRACT
Paraquat is a very toxic herbicide and a dangerous pollutant of the environment. It forms reactive oxygen species and increases the lipid peroxidation in the pulmonary cells. Our aim in this study was to estimate the protective effects of the lazaroid U-74389G possessing antilipidperoxidation activity and membrane-stabilizing effect. The experiment was carried out with 96 male Wistar rats. Paraquat dichloride was administered orally at 80mg/kg. The lazaroid U-74389G was injected intraperitoneally twice - 2h before receiving the paraquat with 10mg/kg and four hours later with 5mg/kg. Isolated application of paraquat increased enzyme activities of lactate dehydrogenase (LDH) and acid phosphatase (AcP) and the total protein content in bronchoalveolar lavage fluid (BALF). In the same experimental group the number of polymorphonuclear cells (PMNs) in BALF is elevated significantly on days 1 and 3. The combined treatment with paraquat and U-74389G did not increase the total protein content and the number of PMNs and it elevated the enzyme activities of LDH and AcP significantly less than the alone application of paraquat. It is concluded that the lazaroid U-74389G reduces the pneumotoxic effects of paraquat, estimated by sensitive cytologic and biochemical markers in BALF. The protective effect of U-74389G is well-expressed until day 3 after the treatment.
