파라콰트 중독 흰쥐에서 항산화제 U-74389G의 치료 효과

Abstract

Background: This study was conducted to verify the hypothesis that the suppression of lipid peroxidation with the antioxidant, U-74389G, could improve the survivability of paraquat intoxicated rats. Methods: First, we obtained the 24-h mortality by using several paraquat dosages and calculated the 24-h LD50 in 24 male Wistar rats(250~350 g). To examine the effect of U-74389G, we divided the rats in 4 groups: a control group and U-74389G only group, a paraquat only group, and a paraquat plus U-74389G group(n=10 each). Paraquat, 35 mg/kg, was injected intraperitoneally at 0 h. U-74389G, 10mg/kg, was administered intraperitoneally at 0, 12 h or at 1, 12 h in the respective groups. The rats were observed for 24 hours. At 24 h, plasma and lung, liver, and idney tissues were obtained after sacrificing the surviving rats to determine the degree of lipid peroxidation by using a thiobarbituric acid reactive substances(TBARS) quantitative analysis. Results: The 24-h LD50 of paraquat was calculated as 40 mg/kg in our rats. The 24-h mortality was as follows: control group and U-74389G group 0%, paraquat group 30%, and paraquat plus U-74389G group 10%. The TBARS analysis showed no differences between the U-74389G and the control groups. The paraquat group showed significantly increased TBARS levels in the serum and in the kidney and lung tissue compared to the control group(p<0.05). With U-74389G, the increased TBARS levels were significantly decreased in the plasma, kidney, and lung tissues compared to the paraquat group(p<0.05). However, in the liver tissue, there were no significant differences among the groups. Conclusion: A 21-aminosteroid antioxidant, U-74389G, improved the survivablity of paraquatintoxicated rats through the suppression of lipid peroxidation. Our result suggests the possibility of clinical application of this drug as an antidote for paraquat poisoning.