Paradoxical dose- and time-dependent regulation of superoxide dismutase and antioxidant capacity by vitamin E in rat

Background: Previous data about the regulation of SOD activity as the key part of the endogenous antioxidant system by vitamin E is conflicting. Methods: We investigated the effect of different nontoxic doses of vitamin E on erythrocyte SOD activity and plasma total antioxidant capacity in rats, receiving 0 (control group), 100, 300 and 600 mg vitamin E/kilogram of body weight intramuscularly twice a week over 6-weeks. Results: We observed a linear increase in SOD activity in the first dosing group, which was significant (p < 0.05) after 6th week compared to the control level. There was an increase in SOD activity at the end of 2nd and significant increase after 4th weeks, which was followed by a significant decrease at the end of 6th week in the second dosing group. In the third dosing group, there was a significant increase at the end of 2nd week and a significant decrease at the end of 4th and 6th weeks in the SOD activity. The changes in plasma antioxidant capacity were parallel to that of SOD activity with a significant and strong degree of correlation in the 4th and 6th weeks (r = 0.7 and r = 0.8, respectively). Serum levels of Vitamin E also increased in a time- and dose-dependent manner; the highest level was achieved in the 600 mg/kg dosing group after 6 weeks. Conclusions: Non-toxic doses of vitamin E at some levels can up-regulate SOD activity, but cumulative effect of the same doses can lead to attenuation of SOD activity and hence antioxidant defense. (c) 2005 Elsevier B.V. All rights reserved.