Efeito do quefir sobre os sistemas cardiovascular e renal em camundongos submetidos ao modelo de estresse crônico

Abstract

Chronic stress affects thousands of people worldwide and brings with it changes that can trigger a series of diseases, reducing the quality of life. In stressful situations there is a direct activation of the hypothalamus-pituitary axis, which releases glucocorticoids, responsible for the increase in oxidative stress and the development of chronic diseases. On the other hand, several studies have shown kefir as a promising product in preventing oxidative damage and reducing anxiety. The aim of this study was to assess oxidative damage caused by unpredictable chronic stress and to verify whether treatment with kefir would prevent them. For this, Swiss mice were divided into 4 groups (milk control, kefir control, milk stress and kefir stress). The animals in the stress groups were subjected to unpredictable chronic stress induction for 20 days. Both control and stress animals were treated with kefir for 30 days (10 before the start of stress induction and during the induction protocol). The animals' weight was monitored throughout the protocol. At the end of the experimental protocol, the elevated plus-maze behavioral test was performed. After euthanizing the animals, blood, heart and kidneys were collected for the following biochemical analyzes: corticosterone levels, renal function assessment, renal and cardiac oxidative stress levels (superoxide dismutase (SOD) activity, catalase and levels glutathione (GSH), determination of lipid peroxidation (TBARS) and immunohistochemistry for 3-nitrotyrosine and determination of metalloproteinase-2 (MMP-2) by zymography and immunohistochemistry). The procedures were approved by CEUA / UNIFAL (61/2018). Statistical analysis: ANOVA two way, followed by Sidak’s post-hoc test (p <0.05). There was a change in body weight of animals submitted to stress (p <0.05) with 10 days of protocol, but there were no significant differences with 20 days of protocol (p> 0.05). In addition, there were changes in behavioral tests towards an increase in anxious behavior, as well as in corticosterone levels (p <0.05) in animals subjected to chronic stress and kephir was able to attenuate this behavior (p <0.05). There were no significant differences in renal assessment between groups (p> 0.05). However, kefir alone led to a significant decrease in creatinine levels (p <0.05). In addition, there were no changes in the renal and cardiac levels of GSH and TBARS, nor in the activity of SOD and CAT (p> 0.05). However, there was an increase in the activity of the SOD and CAT enzymes in animals that consumed kefir and were subjected to stress in both tissues (p <0.05). There were no changes in the levels of nitrotyrosine and MMP-2 in the cardiac tissue (p> 0.05). In the renal tissue, an increase in the levels of 3-nitrotyrosine and MMP-2 was demonstrated in the animals that were submitted to stress in relation to the control groups (p <0.05) and the treatment with the kefir was able to revert only the levels of MMP -2 (p <0.05). Therefore, our study suggests that kefir has anxiolytic properties capable of reversing the effects of unpredictable chronic stress, in addition to acting on antioxidant enzymes regulating its levels or decreasing the production of free radicals.