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      Voluntary exercise improves spermatogenesis and testicular apoptosis in type 2 diabetic rats through alteration in oxidative stress and mir-34a/SIRT1/p53 pathway

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          Abstract

          Objective(s):

          This research was designed to demonstrate the impact of voluntary exercise on sperm parameters including sperm count, morphology, motility, viability, testicular apoptosis, oxidative stress, and the mir-34a/SIRT1/p53 pathway in type 2 diabetic rats.

          Materials and Methods:

          32 Wistar male rats were separated into four groups: control (C), voluntary exercise (VE), diabetic (D), and diabetic rats that performed voluntary exercise (VED). To induce diabetes, animals were injected with streptozotocin (35 mg/kg) after receiving a high-fat diet. The testicular protein levels of SIRT1 and P53, miR-34a expression, MDA, GPx, SOD, catalase, and sperm parameters were evaluated.

          Results:

          Diabetes caused increased testicular MDA content, miR-34a expression, acetylated p53 protein expression, and the percent of immotile sperm ( P<0.01 to P<0.001) as well as reduced testicular GPx, SOD and catalase activities, SIRT1 protein expression, and sperm parameters ( P<0.05 to P<0.001). Voluntary exercise reduced testicular MDA content, miR-34a, and acetylated p53 protein expression compared with the D group ( P<0.001), however, GPx, SOD, catalase activities, and sperm parameters in voluntarily exercised rats were elevated compared with diabetic rats ( P<0.05 to P<0.001).

          Conclusion:

          It seems that voluntary exercise has significant positive impacts that can be employed to reduce the complications of type 2 diabetes in the testis of male rats.

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          Most cited references69

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          Transcriptional activation of miR-34a contributes to p53-mediated apoptosis.

          p53 is a potent tumor suppressor, whose biological effects are largely due to its function as a transcriptional regulator. Here we report that, in addition to regulating the expression of hundreds of protein-coding genes, p53 also modulates the levels of microRNAs (miRNAs). Specifically, p53 can induce expression of microRNA-34a (miR-34a) in cultured cells as well as in irradiated mice, by binding to a perfect p53 binding site located within the gene that gives rise to miR-34a. Processing of the primary transcript into mature miR-34a involves the excision of a 30 kb intron. Notably, inactivation of miR-34a strongly attenuates p53-mediated apoptosis in cells exposed to genotoxic stress, whereas overexpression of miR-34a mildly increases apoptosis. Hence, miR-34a is a direct proapoptotic transcriptional target of p53 that can mediate some of p53's biological effects. Perturbation of miR-34a expression, as occurs in some human cancers, may thus contribute to tumorigenesis by attenuating p53-dependent apoptosis.
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            Diabetes, oxidative stress, and antioxidants: a review.

            Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options. Copyright 2003 Wiley Periodicals, Inc.
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              Oxidative stress, insulin signaling, and diabetes.

              Oxidative stress has been implicated as a contributor to both the onset and the progression of diabetes and its associated complications. Some of the consequences of an oxidative environment are the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction, which can lead ultimately to the diabetic disease state. Experimental and clinical data suggest an inverse association between insulin sensitivity and ROS levels. Oxidative stress can arise from a number of different sources, whether disease state or lifestyle, including episodes of ketosis, sleep restriction, and excessive nutrient intake. Oxidative stress activates a series of stress pathways involving a family of serine/threonine kinases, which in turn have a negative effect on insulin signaling. More experimental evidence is needed to pinpoint the mechanisms contributing to insulin resistance in both type 1 diabetics and nondiabetic individuals. Oxidative stress can be reduced by controlling hyperglycemia and calorie intake. Overall, this review outlines various mechanisms that lead to the development of oxidative stress. Intervention and therapy that alter or disrupt these mechanisms may serve to reduce the risk of insulin resistance and the development of diabetes. Published by Elsevier Inc.
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                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                ijbms
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                January 2021
                : 24
                : 1
                : 58-65
                Affiliations
                [1 ]Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
                [2 ]Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                [3 ]Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
                [4 ]Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
                Author notes
                [* ]Corresponding author: Rana Keyhanmanesh. Department of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran. Tel/Fax: +98-41-33364664; Email: keyhanmaneshr@tbzmed.ac.ir
                Article
                10.22038/ijbms.2020.49498
                7894640
                33643571
                2ee434ba-3eef-45a1-9fe7-2a92bf6b91ae

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 June 2020
                : 7 November 2020
                Categories
                Original Article

                apoptosis,mir-34a,oxidative stress,p53,sperm parameters,type 2 diabetes,voluntary exercise

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