RESUMO
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.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glicemia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Masculino , Oxirredução , Estresse Oxidativo , Quercetina/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Even 30 years after the accident, an association between breast cancer incidence and ionizing radiation exposure from Chernobyl fallout remains uncertain. We studied breast cancer incidence in the most contaminated regions of Belarus (Gomel and Mogilev) and Ukraine (Kyiv, Zhytomyr and Chernihiv) before (1978-1986) and after (1987-2016) the accident. Breast cancer cases and female population size data were received from the national cancer registries and the state departments of statistics. The study included 85 132 breast cancers with 150 million person-years at risk. We estimated annual rayon (district)-average absorbed doses to the breast from external and internal irradiation of the adult female population over the period of 1986-2016. We studied an association between rayon-average cumulative absorbed breast dose with 5-year lag, that is, excluding the exposure in 5 years prior to breast cancer diagnosis, and breast cancer incidence using negative binomial regression models. Mean (median) cumulative breast dose in 2016 was 12.3 (5.0) milligray (mGy) in Belarus and 5.7 (2.3) mGy in Ukraine, with the maximum dose of 55 mGy and 54 mGy, respectively. Breast cancer incidence rates statistically significantly increased with calendar year and attained age, and were higher in urban than in rural residents. Adjusting for time, age and urbanicity effects, we found no evidence of increasing incidence with rayon-average 5-year lagged cumulative breast dose. Owing to ecological study design limitations, a case-control study covering this area with individually reconstructed absorbed breast doses is needed testing for association between low-dose protracted radiation exposure and breast cancer risk after Chernobyl.