Administração associativa do cloridrato de metformina e melatonina na reversão da policistose ovariana e os efeitos sobre o fígado e reprodução em ratas albinas

Abstract

The polycystic ovary syndrome (PCOS) is endocrine disorder in women of reproductive age extremely common and heterogeneous clinical features. In cases of patients with ovarian polycystic wishing to treat infertility, metformin hydrochloride is the drug most widely used and considered safer compared to the other treatments. When diagnosing the syndrome, it has been observed that women have a high prevalence of nonalcoholic fatty liver disease, steatosis, fibrosis, abnormal liverenzyme factors and increased indicators of oxidative stress in plasma, raising concern among doctors about the disease in the liver. Furthermore, recent studies have linked oxidative stress in the pathogenesis of diseases which cause infertility, for this reason, research has suggested the use of antioxidants such as melatonin, due to liver protecting effect in the pharmacological treatment or supplementation to combat these types of disease. However, there are no reports in the literature about association of metformin hydrochloride and melatonin for the treatment of PCOS. The objective of this work was to investigate the effects of combination therapy of these drugs in rats induced to PCOS on to reproductive and liver. Thus, we used 75 albino rats were divided randomly into five groups of 15 animals. All rats except those in group I were subjected to induction of PCOS by constant illumination, and the rats of groups III, IV and V received treatment with the drug melatonin, metformin hydrochloride and the drug combination, respectively. After confirmation of PCOS and treatments, we analyzed the effects of plasma biochemical and hormonal treatments, and rats were mated and monitored during pregnancy for analysis of implantation sites, ovarian, weight gain, reproductive viability and levels of oxidative stress. At the end of the experiment was conducted histopathology, and immunohistochemistry staining of liver of rats and analysis of the puppies. Pharmacological treatments decreased the time allowed copulation, increased plasma levels of progesterone, the number and weight of pups and reduced plasma levels of estrogen and endometrial content of collagen fibers. In the liver, treatment with metformin hydrochloride, melatonin and more significantly the association of these drugs reduced plasma levels of the liver enzyme alanine trasaminase, nitric oxide and total glutathione, leading to results similar to the control group, were also observed similarities between those of control rats and rats that received a combination of drugs for the content of hepatic polysaccharide, and of proinflammatory cytokines. Thus, we conclude that the association of metformin with melatonin provides the best results compared to the other treatments, in order to regulate hormonal and histochemical the reproductive system and increase the chance of conception resembling the control group, and the liver, the combination of drugs works more effectively against liver toxicity produced by PCOS, favoring normalization of biochemical parameters and oxidative stress during pregnancy, compared to therapies only these drugs.