Stress-induced cardiometabolic perturbations, increased oxidative stress and ACE/ACE2 imbalance are improved by endurance training in rats.

AIMS: To investigate the effects of endurance training on stress-induced cardiometabolic perturbations given the elevated release of stress hormones and subsequent glucose homeostasis perturbations. MATERIALS AND METHODS: Rats were randomized into non-trained rats, rats submitted to endurance training, non-trained rats submitted to stress, and trained rats submitted to stress. Endurance training was applied for 8 weeks, while chronic stress was applied at the 4th, 5th, and 6th weeks of the training period. Two weeks after the last stressor stimuli, rats were euthanized, and blood and heart were collected for biochemical tests. KEY FINDINGS: Exacerbated corticosterone levels were observed in both stressed groups, and chronic stress per se impaired glucose tolerance and insulin sensitivity. Training reduced circulating adrenaline, even though noradrenaline levels were elevated in the blood and heart of trained rats. While stress-induced high circulating serotonin levels were further increased by endurance training, cardiac serotonin levels were attenuated in trained rats. Endurance training mitigated the stress-induced higher circulating lipids. Cardiac TBARs and GPx activity increased in trained rats while CAT and GPx were reduced in response to chronic stress. Endurance training not only attenuated the stress-induced higher circulating ACE/ACE2 ratio but also reduced ACE/ACE2 balance in the heart. Glucose intolerance, insulin resistance, and altered stress hormones release were linked to impairment of cardiometabolic responses, elevated oxidative stress, and dysregulation of ACE/ACE2 ratio. SIGNIFICANCE: Endurance training mitigated the stress-related pathophysiological responses, which could be related to improvements in the antioxidant capacity and the balance of ACE/ACE2 activity.

Saccharomyces boulardii exerts renoprotection by modulating oxidative stress, renin angiotensin system and uropathogenic microbiota in a murine model of diabetes.

AIMS: We aimed to investigate whether Saccharomyces boulardii strain might exert renoprotective effects by modulating renal renin angiotensin system, oxidative stress and intestinal microbiota in streptozotocin-diabetic mice. MAIN METHODS: Thirty-six C57BL/6 male mice were divided into four groups: control (C), control + probiotic (CP), diabetes (D), diabetes + probiotic (DP). Diabetes was induced by one intraperitoneal injection of streptozotocin and Saccharomyces boulardii was administered by oral gavage for 8 weeks. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7) and the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined, besides that, renal morphology, serotonin and dopamine levels and also microbiota composition were analyzed. KEY FINDINGS: Probiotics significantly increased C-peptide secretion and reduced blood glucose of diabetic animals. Saccharomyces boulardii also improved renal antioxidant defense, restored serotonin and dopamine concentration, and activated the renin-angiotensin system (RAS) vasodilator and antifibrotic axis. The modulation of these markers was associated with a beneficial impact on glomerular structure and renal function of diabetic treated animals. The phenotypic changes induced by Saccharomyces boulardii were also related to modulation of intestinal microbiota, evidenced by the decreased abundance of Proteus and Escherichia-Shigella, considered diabetic nephropathy biomarkers. SIGNIFICANCE: Therefore, probiotic administration to streptozotocin-induced diabetic mice improves kidney structure and function in a murine model and might represent a reasonable strategy to counteract nephropathy-associated maladaptive responses in diabetes.