Time- and dose-dependent differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase enzymatic activity and mRNA level by vitamin E in rat blood cells

摘要

Background: Vitamin E is the most important lipid-soluble antioxidant. Recently, it has been proposed as angene regulator, and its gene modulation effects have been observed at different levels of gene expressionnand cell signaling. This study was performed to investigate the effects of vitamin E on the activity andnexpression of themost important endogenous antioxidant enzyme, superoxide dismutase (SOD), in rat plasma.nMethods: Twenty-eight male Sprauge–Dawley rats were divided into four groups: control group and threendosing groups. The control group received the vehicle (liquid paraffin), and the dosing groups receivedntwice-weekly intraperitoneal injections of 10, 30, and 100 mg/kg of vitamin E ((±)-α-Tocopherol) forn6 weeks. Quantitative real-time reverse transcription-polymerase chain reaction and enzyme assays werenused to assess the levels of Cu/Zn-SOD and Mn-SOD mRNA and enzyme activity levels in blood cells atn0, 2, 4, and 6 weeks following vitamin E administration. Catalase enzyme activity and total antioxidantncapacity were also assessed in plasma at the same time intervals.nResults: Mn-SOD activity was significantly increased in the 100 and 30 mg/kg dosing groups after 4 andn6 weeks, with corresponding significant increase in their mRNA levels. Cu/Zn-SOD activity was notnsignificantly changed in response to vitamin E administration at any time points, whereas Cu/Zn-SODnmRNA levels were significantly increased after longer time points with high doses (30 and 100 mg/kg) ofnvitamin E. Catalase enzyme activity was transiently but significantly increased after 4 weeks of vitamin Entreatment in 30 and 100 mg/kg dosing groups. Total antioxidant status was significantly increased aftern4 and 6 weeks in the 100 mg/kg dosing group.nConclusion: Only the chronic administration of higher doses of alpha-tocopherol is associated with thenincreased activity and expression of Mn-SOD in rats. Cu/Zn-SOD activity and expression does notndramatically change in response to vitamin E