Objective. Emerging data indicate that oxidative stress is closely associated with the pathogenesis of cardiovascular disease in type 2 diabetes mellitus (T2DM). The present study aimed to assess the effect of the most abundant flavonoid in the human diet quercetin (Q) on the myocardial redox status in rats with T2DM. Methods. T2DM was induced in male Wistar rats by a high caloric diet (for 14 weeks) and two streptozotocin (25 mg/kg b.w.) injections applied in four weeks of the diet, once a week for two weeks. The Q was administered intragastrically by gavage in a dose of 10 or 50 mg/kg of the body weight for 8 weeks starting from the 8th day after the last streptozotocin injection. The control rats received citrate buffer and seven days after the last STZ injection, basal glucose levels were measured in all animals. Results. Administration of Q increased insulin sensitivity in diabetic rats with more pronounced effect at a dose of 50 mg/kg b.w. The Q also decreased free radical oxidation in the heart mitochondria of diabetic animals, thus limiting the formation of advanced oxidation protein products in a dose-dependent manner and normalized the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase) in cardiac mitochondria independently of the dose used. In addition, the Q in both doses prevented the development of oxidative stress in the T2DM rats cardiomyocytes by reducing NADPH oxidase and xanthine oxidase activities. Conclusions. The findings demonstrate that Q in both doses 10 mg/kg and 50 mg/kg can protect from the development of oxidative stress in cardiomyocytes in the diabetic rats. The present data indicate that the use of Q may contribute to the amelioration of cardiovascular risk in patients with T2DM.
The effect of 17β-estradiol on the heme oxygenase activity and TBA-active products level in vessels of variectomized rats with insulin resistance was investigated. Insulin resistance induced by high fructose diet in ovariectomized rats led to increase in heme oxygenase activity and TBA-active products level in vessels. Administration of 17β-estradiol prevented increase in heme oxygenase activity and TBA-active products level, that could be explained by amelioration of insulin resistance and normalization of prooxidant-antioxidant state and could be considered the one of possible mechanisms of vasoprotective estradiol effect.
Dysfunction of cardiac mitochondria appears to play a substantial role in cardiomyopathy and is a promising therapeutic target for many cardiovascular diseases. Persistent hyperglycaemia and hyperlipidemia are believed to be the main causes of increased oxidative stress, mitochondrial dysfunctions, fibrosis and apoptosis of cardiomyocytes in diabetes. We have previously shown that the low-toxic succinate derivative – Phensuccinal (beta-phenylethylamide-2 hydroxy-succinanylic acid, Phe) possesses antioxidant and anti-inflammatory properties. The aim of this study was to assess the effects of Phe on the mitochondrial function and oxidative status in the heart of rats with T2DM. Materials and Methods. T2DM was induced in Wistar rats by a high-caloric diet during 14 weeks combined with intraperitoneal injections of 25 mg/kg streptozotocin twice per week. All diabetic animals were divided into two groups: treated with vehicle or with Phe (in dose 50 mg/kg/day) for four weeks after diabetes induction. Redox status of rats’ heart mitochondria was estimated by determination of reactive oxygen species (ROS) production, GSH level and activity of antioxidant enzymes (Mn-superoxide dismutase, glutathione peroxidase and glutathione reductase). Mitochondrial function was determined by activity of aconitase, succinate dehydrogenase and cytochrome C oxidase in rats’ cardiomyocytes. Results. It was established that Phe inhibited oxidative stress in isolated heart mitochondria of rats with T2DM, which was confirmed by decreasing ROS production and increasing GSH level compared to diabetic rats. The use of Phe led to a normalization of antioxidant enzymes (Mn-superoxide dismutase and glutathione peroxidase) activity in the heart of diabetic rats. In addition, Phe improved metabolic activity of the heart mitochondria activating aconitase and succinate dehydrogenase in cardiomyocytes. We can suggest that Phe ameliorate mitochondrial dysfunction decreasing oxidative stress and preventing deficiency in complex II of ETC in the heart of rats with type 2 diabetes. Conclusion. The data of the present study confirmed the positive effect of Phe on redox homeostasis and functional state of the heart mitochondria in diabetic rats. We suggest that the use of Phe may contribute to the amelioration of cardiovascular risk in type 2 diabetes
Роботу виконано згідно з плановою науковою тематикою лабораторії біохімічних досліджень ДУ «Інститут проблем ендокринної патології ім. В. Я. Данилевського НАМН України» «Визначення біохімічних та функціональних порушень, які обумовлюють статевий диморфізм основних чинників кардіоваскулярного ризику за умов цукрового діабету 2 типу», (державний реєстраційний № 0116U000332). Установою, що фінансує дослідження, є НАМН України. Автори гарантують колективну відповідальність за все, що опубліковано в статті. Автори гарантують відсутність конфлікту інтересів та фінансової зацікавленості при виконанні роботи та написанні статті. Рукопис надійшов до редакції 13.02.2019.
Type 2 diabetes mellitus is known to double mortality from cardiovascular diseases (cVD), in which oxidative stress plays an important role. It is suggested that the impact of diabetes on cVD risk may vary depending on gender. The aim of the study was to assess oxidative stress parameters in the heart of 12 weeks old male and female Wistar rats with type 2 diabetes mellitus (T2DM) induced by high-calorie diet followed by intraperitoneal streptozotocin injections. The level of advanced oxidation protein products, superoxide dismutase, glutathione reductase and glutathione peroxidase activity in the isolated heart mitochondria and NaDph-oxidase and xanthine oxidase activity in the post-mitochondrial supernatant fraction were determined. it was shown that t2DM induced more pronounced oxidative stress confirmed by the increased level of advanced oxidation protein products in the heart mitochondria of males than females. The data obtained indicate that the main reason of oxidative stress in the heart of diabetic males is the activation of non-mitochondrial sources of reactive oxygen species. While in the heart of diabetic female rats it is the decrease in antioxidant enzymes activity in mitochondria. these results justify the necessity of gender-specific therapy for the prevention and management of diabetic cVD.
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