Saccharomyces boulardii modulates oxidative stress and renin angiotensin system attenuating diabetes-induced liver injury in mice

Leticia Barssotti,Isabel C M E Abreu,Carla R Taddei,Kátia De Angelis,Miguel A C Salgado,Dulce E Casarini,Lívia B Souza,Rodrigo Yokota,Raquel C M F Albuquerque,Danielle D S Dias,Fabiana G Ferreira,Tatiana S Cunha,Ana Beatriz P Brandão

doi:10.1038/s41598-021-88497-w

Leticia Barssotti, Isabel C M E Abreu + Show 11 more

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https://doi.org/10.1038/s41598-021-88497-w

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Abstract

Type 1 diabetes (T1DM) is a chronic disease characterized by hyperglycemia due to a deficiency in endogenous insulin production, resulting from pancreatic beta cell death. Persistent hyperglycemia leads to enhanced oxidative stress and liver injury. Several studies have evaluated the anti-diabetic and protective effects of probiotic strains in animal models. In the present study, we investigated, through histopathological and biochemical analyses, the effects of eight weeks of administration of Saccharomyces boulardii (S. boulardii) yeast on the liver of streptozotocin (STZ) induced diabetic C57BL/6 mice. Our results demonstrated that S. boulardii attenuates hepatocytes hydropic degeneration and hepatic vessels congestion in STZ-induced diabetic mice. The treatment attenuated the oxidative stress in diabetic mice leading to a reduction of carbonylated protein concentration and increased activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase, compared to untreated diabetic animals. The results also show the beneficial influence of S. boulardii in regulating the hepatic concentration of renin angiotensin system (RAS) peptides. Therefore, our results demonstrated that S. boulardii administration to STZ-induced diabetic mice reduces oxidative stress and normalizes the concentration of RAS peptides, supporting the hypothesis that this yeast may have a role as a potential adjunctive therapy to attenuate diabetes-induced liver injury.

Highlights

Type 1 diabetes (T1DM) is a chronic disease characterized by hyperglycemia due to a deficiency in endogenous insulin production, resulting from pancreatic beta cell death
The diabetic group that received a daily dose of S. boulardii presented a 30% reduction of blood glucose compared to the untreated group (DP = 251.9 ± 36.40 mg/dl vs. D = 362.9 ± 21.26 mg/dl), showing the beneficial effect of the probiotic on glucose homeostasis (Fig. 1b)
Some studies have already evaluated the anti-diabetic effects of probiotic strains in animal models[16,34,35,36,37], as well as the close association between the gut microbiota and the development of liver injury[19,21,23,38,39,40]

Summary

Introduction

Type 1 diabetes (T1DM) is a chronic disease characterized by hyperglycemia due to a deficiency in endogenous insulin production, resulting from pancreatic beta cell death. Our results demonstrated that S. boulardii administration to STZ-induced diabetic mice reduces oxidative stress and normalizes the concentration of RAS peptides, supporting the hypothesis that this yeast may have a role as a potential adjunctive therapy to attenuate diabetes-induced liver injury. The formation of ROS combined with a decrease in the antioxidant defense leads to an increase in oxidative stress, which in turn can cause oxidation of proteins and lipids, excessive activation of pro-inflammatory pathways and DNA damage. In the liver, these cell injuries are associated with hepatocyte necrosis and a poptosis[7,8,9]. The local RAS might affect tissue angiogenesis, proliferation, cell growth, apoptosis, tissue inflammation and fibrosis, stimulating insulin resistance, de novo lipogenesis and mitochondrial dysfunction, especially during injury[15]

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