Experimental skin ischemia in rats was induced by suturing a skin fold on the back with a silk thread. Combined pretreatment with superoxide dismutase (intraperitoneally) and Reamberin (intravenously) in doses of 0.01 and 6.25 mg/kg (by succinate concentration), respectively, produced a strong protective effect on the skin. The index of cytolysis decreased by 39%. The more pronounced antinecrotic effect of combined treatment with superoxide dismutase and Reamberin compared to the effect of Reamberin alone was related to a sharp increase in the reserve capacity of the antioxidant system. After combined therapy, activity of antioxidant defense enzymes not only increased, but even exceeded the normal level. The increase in activity of endogenous superoxide dismutase under the influence of combined therapy was accompanied by suppression of superoxide anion production.

Antinecrotic activity of SOD was studied in rats with experimental skin ischemia. Treatment with SOD increased activity of endogenous SOD in skin homogenates (by 70 and 26% compared to the ischemic and intact skin, respectively). However, the rate of superoxide anion generation remained unchanged after SOD treatment. Creatine phosphate content and NAD/NADH redox potential increased by 16 and 21%, respectively, on day 3 after SOD administration. The increase in functional activity of the energy supply system and rise in the reserve capacity of the antioxidant protection system contribute to inhibition of lactate dehydrogenase and creatine phosphokinase and decrease in the cytolysis index under the influence of SOD. Our results indicate that SOD produces the antinecrotic effect and holds much promise for the therapy of skin ischemia.

Reamberin in a dose of 25 mg/kg (succinate concentration) was injected intravenously for 3 days starting from the 1st hour after skin ischemia modeling. This treatment decreased activities of lactate dehydrogenase, aspartate transaminase, and creatine phosphokinase in skin homogenates by 1.6 times, 19%, and 51.3%, respectively. The index of cytolysis decreased by 18%. Reamberin had an energotropic effect, which manifested in an increase in the total ATP content and concentration of creatine phosphate (by 16 and 10%, respectively). After administration of Reamberin, activity of the succinate-ubiquinone reductase system increased by 17%. Under these conditions succinate dehydrogenase activity exceeded the normal by 21%. Reamberin had no effect on the mitochondrial NADH-ubiquinone reductase system in dermal cells during skin ischemia. Superoxide dismutase activity in the area of necrosis increased to the control level on day 3 of treatment with Reamberin. Activities of catalase and glutathione peroxidase increased by 13 and 19%, respectively. Our results indicate that the course of intravenous treatment with Reamberin for 3 days contributes to an increase in reserve capacities of the antioxidant protection system and produces a protective effect during skin ischemia.