Oxidative stress is a major cause of various types of tissue damage, especially endothelial dysfunction, which occurs in diabetes mellitus. In a healthy organism the formation of ROS occurs under the strict control of the biological system, on the contrary, under severe stress, many diseases, as well as diabetes, the production of ROS increases curtly. Due to its high reactivity, an increase in the amount of SOR leads to oxidative stress, which disturb the balance between the antioxidant and prooxidant systems. The main prin-ciple of the therapeutic strategy to reduce oxidative stress in diabetes mellitus is to inhibit the formation of free radicals. The results of clinical and experimental experiments demonstrate the administration of antioxidants, especially vitamin E, insulin resistance and therapeutic effect in diabetic conditions. Recently, the use of synthetic, as well as herbal antioxidants, along with other drugs in the pharmacotherapeutic correction of a number of pathologies in medical practice has become widespread. The development of a more effective pharmacotherapeutic strategy for diabetes with antioxidants and the synthesis of potent agents are promising for further research. Key words: diabetes mellitus, antioxidant, oxidative stress, reactive oxygen species (ROS), free radicals

Aim. To define the effect of calcium channel blockers long-term use on blood level of luteinizing hormone and estradiol in female rats. Methods. 82 mature female outbreed rats were distributed to seven groups. The rats of the first (control) group were administered 0.2 ml of 0.9% saline intraperitoneally for 21 day. Instead of saline, 5 and 25 mg/kg of verapamil were used in rats of the second and third groups, 5 and 10 mg/kg of nifedipine - in rats of the 4th and 5th groups, 5 and 20 mg/kg of diltiazem - in rats of the 6th and 7th groups accordingly. Blood levels of luteinizing hormone and estradiol were determined by ELISA after animals were withdrawn from the study. Results. In rats treated with calcium channel blockers, a dose-dependent decrease of luteinizing hormone and estradiol blood levels were observed. High doses of verapamil (group 3) decreased the level of luteinizing hormones and estradiol by 50% compared to control group, high doses of diltiazem (group 7) - by 50%. Only minor changes were observed in rats who were administered nifedipine, even in high doses. Conclusion. Observed decrease of blood estradiol level indicate the influence of calcium channel blockers directly on ovarian function; decrease of blood luteinizing hormone level might by secondary due to positive feedback between the estradiol and luteinizing hormone secretion and reflect decreased estradiol blood level.

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