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      Antioxidant action of alpha lipoic acid on the testis and epididymis of diabetic rats: morphological, sperm and immunohistochemical evaluation

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          ABSTRACT

          Introduction

          Chronic hyperglycemia is caused by diabetes mellitus-committed genital morphophysiology, and oxidative stress is one of the main factors involved in this process. Alpha lipoic acid (ALA) can prevent metabolic and morphological changes in diabetic individuals.

          Objectives

          In present study, we evaluated the effects of regular ALA consumption on the spermatogenesis and histoarchitecture in the male genital system of diabetic rats.

          Materials and Methods

          Thirty-two Wistar rats were divided into groups: Control (CG); Diabetic Control (DCG), receiving commercial diet: ALA Group (ALAG) and Diabetic ALA Group (DALAG), fed diets with added ALA (300 mg/Kg bw). The diabetic groups received a single injection of streptozotocin (60 mg/kg). After sixty days of the diet, the animals were euthanized, and semen, testis and epididymis samples were collected. A histomorphometric analysis was performed to determine the epithelial height, tubular and luminal diameter, tubular and luminal area of seminiferous tubules and each epididymal region. Sertoli cells were evidenced using the antivimenti antibody and were quantified. The results were statistically analyzed by the ANOVA test.

          Results

          At the end of the experiment, the DALAG glycemia was significantly lower than DCG. The histomorphometric parameters of the seminiferous and epididymal tubules did not show improvement in the DALAG. However, there was an improvement in the DALAG in terms of the concentration, motility and percentage of spermatic pathologies, as well as in the number of Sertoli cells (p<0.001).

          Conclusions

          The results demonstrated that supplementation with the ALA antioxidant retards testicular lesions and preserve the process of spermatogenesis in diabetes.

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          Most cited references31

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          Definition of the stages of the cycle of the seminiferous epithelium in the rat.

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            Insulin dependant diabetes mellitus: implications for male reproductive function.

            Diabetes mellitus (DM) is increasing in men of reproductive age. Despite this, the prevalence of diabetes in men attending fertility clinics is largely unknown. Furthermore, studies examining the effects of DM on sperm fertility potential have been limited to conventional semen analysis. Conventional semen analysis (semen volume, sperm count, motility and morphology) was performed for 27 diabetic (mean age 34+/-2 years) and 29 non-diabetic subjects (control group, men undergoing routine infertility investigations, mean age 33+/-1 years). Nuclear DNA (nDNA) fragmentation was assessed using the alkaline Comet assay and mitochondrial DNA (mtDNA) deletions by Long-PCR. Other than a small, but significant, reduction in semen volume in diabetic men (2.6 versus 3.3 ml; P<0.05), conventional semen parameters did not differ significantly from control subjects. Diabetic subjects had significantly higher mean nDNA fragmentation (53 versus 32%; P<0.0001) and median number of mtDNA deletions (4 versus 3; P<0.05) compared with control subjects. Diabetes is associated with increased sperm nuclear and mtDNA damage that may impair the reproductive capability of these men.
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              Lipoic acid - biological activity and therapeutic potential.

              α-Lipoic acid (LA; 5-(1,2-dithiolan-3-yl)pentanoic acid) was originally isolated from bovine liver by Reed et al. in 1951. LA was once considered a vitamin. Subsequently, it was found that LA is not a vitamin and is synthesized by plants and animals. LA is covalently bound to the ε-amino group of lysine residues and functions as a cofactor for mitochondrial enzymes by catalyzing the oxidative decarboxylation of pyruvate, α-ketoglutarate and branched-chain α-keto acids. LA and its reduced form - dihydrolipoic acid (DHLA), meet all the criteria for an ideal antioxidant because they can easily quench radicals, can chelate metals, have an amphiphlic character and they do not exhibit any serious side effects. They interact with other antioxidants and can regenerate them. For this reason, LA is called an antioxidant of antioxidants. LA has an influence on the second messenger nuclear factor κB (NF-κB) and attenuates the release of free radicals and cytotoxic cytokines. The therapeutic action of LA is based on its antioxidant properties. Current studies support its use in the ancillary treatment of many diseases, such as diabetes, cardiovascular, neurodegenerative, autoimmune diseases, cancer and AIDS. This review was undertaken to gather the most recent information regarding the therapeutic properties of LA and its possible utility in disease treatment.
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                Author and article information

                Journal
                Int Braz J Urol
                Int Braz J Urol
                ibju
                International Brazilian Journal of Urology : official journal of the Brazilian Society of Urology
                Sociedade Brasileira de Urologia
                1677-5538
                1677-6119
                2 September 2019
                Jul-Aug 2019
                : 45
                : 4
                : 815-824
                Affiliations
                [1 ] Departamento de Morfologia, Laboratório de Biomorfologia Celular e Extracelular, Universidade Federal Fluminense - UFF, Niterói, RJ, Brasil;
                [2 ] Departamento de Nutrição e Dietética, Nutrição Experimental, Universidade Federal Fluminense - UFF, Niterói, RJ, Brasil;
                [3 ] Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense - UFF, Niterói, RJ, Brasil
                Author notes
                Correspondence address: Mauricio Alves Chagas, PhD Departamento de Morfologia, Laboratório de Biomorfologia Celular e Extracelular. Universidade Federal Fluminense - UFF. Rua Prof. Ernani de Mello, 101 - São Domingos Niterói, RJ, 22210-130, Brasil Telephone: +55 21 2629-2455 ext. 21 E-mail: chagas.m@ 123456gmail.com

                CONFLICT OF INTEREST

                None declared.

                Author information
                http://orcid.org/0000-0002-4873-616X
                Article
                S1677-5538.IBJU.2018.0774
                10.1590/S1677-5538.IBJU.2018.0774
                6837592
                31184457
                95ce5782-e3a2-43ba-ac2a-8ebda6305d8a

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 November 2018
                : 14 April 2019
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 30, Pages: 10
                Funding
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
                Award ID: 001
                Categories
                Original Article

                testis,epididymis,morphological and microscopic findings,spermatozoa

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