백서의 Paraquat 투여에 의한 간과 폐 조직의 산화성 손상에서 Vitamin C 와 Deferoxamine 의 항산화 효과에 관한 연구 = The Antioxidant Effect of Vitamin C and Deferoxamine on Paraquat Induced Lipid Peroxidation in Rats

다국어 초록 (Multilingual Abstract)

Background: The toxicity of paraquat has been known to be caused by oxygen free radicals which leads to the lipid peroxidation and multiple organ failure. Although vitamin C has been known to be a potent antioxidant, recently there are numerous data which have shown that a low dose of vitamin C may act as a prooxidant due to the stimulation of the Fenton reaction with metal ions, which produces hydroxyl radicals. It has been reported that a deferoxamine in paraquat intoxication could reduce the production of the hydroxyl radicals by the inhibition of the Fenton reaction through the reduction of iron ion in tissue. The aim of this study was to evaluate the effect of the high and low dose of vitamin C and deferoxamine on lipid peroxidation and plasma TNF-αin paraquat intoxication. Methods: Female Sprague-Dawley rats were divided into seven groups: control group which was not given paraquat(20 mg/kg), P group which was given paraquat only, PVH group given paraquat and high dose of vitamin C(100 mg/kg), PVL group given paraquat and low dose of vitamin C(10 mg/kg), PVHD given paraquat, high dose of vitamine C and deferoxamine(100 mg/kg), PVLD given paraquat, low dose of vitamin C and deferoxamine, and PD given paraquat and deferoxamine. Animals were killed at 6 and 24 hours after treatment. Malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione(GSH) contents, catalase activity, plasma TNF-α, and histologic changes in the lung and liver tissue were measured. Results: The lung histology in the PVH and PD or PVHD groups showed the significant decreases in the alveolar edema and interstitial thickness compared to the P group. The liver histololgy in the PVH and PVHD groups demonstrated marked differences in the central venous and sinusoidal dilatation compared to that of the P group. While the MDA levels of the lung and liver in the PVH and PD groups showed the significant reduction compared to that of the P group at 6 hours after treatment, all groups showed the significant changes compared to the P group at 24 hours. There was no significant change of the SOD levels of the lung and liver at 6 hours among all groups. At 24 hours, the SOD levels of the lung in PVH, PVL, and PVHD groups showed the significant increases compared to the P group. The increase of the SOD level in groups combined with deferoxamine, however, revealed a little reduction. The SOD level of the liver in PVH group only significantly increased compared to the P group at 24 hours. There was no significant change of the GSH level of the lung and liver among all groups at 6 hours. At 24 hours, the GSH level of the lung and liver were significantly increased in both PVH and PD group and PVH group, respectively, compared to the P group. Although the catalase activity of the lung was not significantly increased, that of liver was significantly increased in both PVHD and PD groups compared to the P group at 6 hours. The catalase activities of the lung and liver were significantly increased in PVH, PD, and PVHD at 24 hours. The concentrations of the plasma TNF-αwere slightly decreased at 6 hours and slightly increased at 24 hours compared to that of the P group, but they were not significant. Conclusion: This study showed that although the low dose of vitamin C had no effect, the high dose of vitamin C revealed a decrease of the MDA level and an increase of SOD, GSH, and catalase activity in the lung and liver tissues, and the effect of the high dose of vitamin C increased with time. The administration of the deferoxamine with or without high dose of vitamin C, however, significantly showed the inhibition of the lipid peroxidation and antioxidant effect and low dose vitamin C decreased the effect of deferoxamine. The effects of the vitamin C and deferoxamine on plasma TNF-αwere not clearly shown.