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ECPB 2019, 88(4): 16–21
https://doi.org/10.25040/ecpb2019.04.016
Research articles

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

O.A. TEMIROVA1, M.V. KHAITOVYCH1, A.P. BURLAKA2, A.V. VOVK2
Abstract

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 investigated. 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 receiving 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 collect blood and brain of rats. Molecular marker of oxidatively damaged DNA in brain – 8-oxoguanine (8-охоG) was 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. NAC significantly reduced the 8-oxoG level by 1.6 times less than in DM1 group (р<0,05). Exposure to Mel significantly reduced the 8-oxoG level by 1.7 times less than in DM1 group (р<0,05). While treatment with combination of NAC and Mel showed significant 2.0-fold decrease of 8-oxoG level compared to DM1 group. 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 blood of experimental animals. Under these conditions, oxidative damage to DNA 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 counteracting oxidative DNA damage.

Received: 28.11.2019

Keywords: type 1 diabetes mellitus, encephalopathy, N-acetylcysteine, melatonin, 8-oxoguanine, “free iron”

Full text: PDF (Ukr) 497K

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