Protector properties of N-acetylcysteine, melatonin and their compatible use for oxidative damage of rat brain cells with experimental diabetes mellitus type 1

Diabetes mellitus (DM) is the most widespread endocrinological disease which associated with increasing risk of Alzheimer’s disease. Diabetic encephalopathy is one of the most common and serious complications of DM. Molecular mechanisms of diabetic encephalopathy are inves-tigated. An important element in the development of DM1 encephalopathy is the activation of oxidative stress. And determination the levels of “free iron” and 8-oxoguanine are important for evaluation of the effectiveness of diabetic encephalopathy therapy. Purpose of the study. To study the effect of N-acetylcysteine, melatonin and their compatible use on the state of oxidative damage of rat brain cells with experimental DM1. Materials and research methods. Experiments were carried out on male Wistar rats. DM1 was induced by administration of streptozotocin (STZ). Rats with induced DM1 was re-ceiving N-acetylcysteine (NAC, 1500 mg/kg), melatonin (Mel, 10 mg/kg) and a combination during 5 weeks, starting at 15 days after control pathology was reproduced. Euthanasia was implemented by decapitation under thiopental anesthesia (40 mg/kg, intraperitoneally) to col-lect blood and brain of rats. Molecular determined by spectrophotometrically. Levels of “free iron” were determined by electron paramagnetic resonance (EPR) on a computerized EPR-spectrophotometer PE-1307. Results and its discussion. During 7-week experiment, the levels of “free iron” in brain tissue and blood in group of animals with DM1 were significantly higher than corresponding values of control group (by 17-times and by 8-times р< 0,05). Under these conditions, the marker of oxidatively damaged DNA, 8-oxoG, significantly raised in brain of diabetic rats by 3.4 times more than in control group (0.61±0.10 nm/g vs 0.18±0.06 nm/g, р< 0,05). The induction of NAC, Mel, and especially their combination, was accompanied with decrease in “free iron” complexes in brain tissues (by 2.1-8.5-times) and blood (by 1.2-1.4-times) of rats with experimental DM1. 0,05). significant 2.0-fold decrease of 8-oxoG Conclusions. Induction of DM1 contributes to the intensification of oxidation processes, which is accompanied by an increasing in the levels of “free iron” complexes in the tissues of the brain and of experimental Under these conditions, oxidative damage to was observed, as evidenced by increasing in the level of 8-oxoG (p <0.05). The induction of N-acetylcysteine, melatonin, and especially their combination, contributed to the antioxidant protection of rat brain cells with experimental DM1, reducing the level of “free iron” and coun-teracting oxidative DNA damage.