Shopova Veneta L, Dancheva Violeta Y, Salovsky Pencho T, Stoyanova Angelina M
Sectors of Disaster Medicine, Medical University-Pleven, Pleven, Bulgaria.
Respirology. 2009 May;14(4):504-10. doi: 10.1111/j.1440-1843.2009.01531.x.
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.
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.
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).
EUK-134, a superoxide dismutase/catalase mimetic compound decreased the pneumotoxic effect of paraquat in rats.
EUK - 134是最具前景的超氧化物歧化酶(SOD)/过氧化氢酶模拟化合物之一。在百草枯肺毒性大鼠模型中测试了EUK - 134的抗氧化作用。
将雄性Wistar大鼠(n = 72)分为三组:第1组为对照组;第2组为单独给予百草枯组;第3组为百草枯 + EUK - 134组。以80 mg/kg的剂量经口给予二氯百草枯。在给予百草枯前2小时腹腔注射10 mg/kg的EUK - 134,4小时后再注射5 mg/kg。
单独给予百草枯治疗后第1、3和5天,乳酸脱氢酶(LDH)活性升高(分别为P = 0.0001、P = 0.00001和P = 0.03),总蛋白含量升高(分别为P = 0.00002、P = 0.001和P = 0.01)。支气管肺泡灌洗液(BAL)中酸性磷酸酶(AcP)水平在第1天和第3天升高(P = 0.006和P = 0.04)。在肺匀浆中,单独给予百草枯在第1天增加了超氧化物歧化酶(SOD)活性,在第3天和第5天降低了该活性。百草枯与EUK - 134联合治疗在第3天(显著低于单独使用百草枯组)和第5天提高了LDH活性,仅在第5天提高了总蛋白含量,且未改变AcP活性。两种药物联合使用未改变SOD活性,并且在第5天过氧化氢酶活性降低的程度明显低于单独使用百草枯治疗(P = 0.05)。
超氧化物歧化酶/过氧化氢酶模拟化合物EUK - 134降低了百草枯对大鼠的肺毒性作用。