Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet-Induced Obese Mice

Oxidative Medicine and Cellular Longevity, Jun 2016

Obesity is prevalent worldwide and is a major risk factor for the development and progression of kidney disease. Hydrogen sulfide (H2S) plays an important role in renal physiological and pathophysiological processes. However, whether H2S is able to mitigate kidney injury induced by obesity in mice remains unclear. In this study, we demonstrated that H2S significantly reduced the accumulation of lipids in the kidneys of high fat diet- (HFD-) induced obese mice. The results of hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining showed that H2S ameliorated the kidney structure, decreased the extent of interstitial injury, and reduced the degree of kidney fibrosis in HFD-induced obese mice. We found that H2S decreased the expression levels of tumor necrosis factor-α, interleukin- (IL-) 6, and monocyte chemoattractant protein-1 but increased the expression level of IL-10. Furthermore, H2S treatment decreased the protein expression of p50, p65, and p-p65 in the kidney of HFD-induced obese mice. In conclusion, H2S is able to mitigate renal injury in HFD-induced obese mice through the reduction of kidney inflammation by downregulating the expression of nuclear factor-kappa B. H2S or its releasing compounds may serve as a potential therapeutic molecule for obesity-induced kidney injury.

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Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet-Induced Obese Mice

Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet-Induced Obese Mice Dongdong Wu,1 Biao Gao,1,2 Mengling Li,1 Ling Yao,1 Shuaiwei Wang,1 Mingliang Chen,1 Hui Li,1 Chunyan Ma,2 Ailing Ji,1 and Yanzhang Li1 1School of Medicine, Henan University, Kaifeng, Henan 475004, China 2Kaifeng Central Hospital, Kaifeng, Henan 475000, China Received 28 March 2016; Revised 6 May 2016; Accepted 8 May 2016 Academic Editor: Guangdong Yang Copyright © 2016 Dongdong Wu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Obesity is prevalent worldwide and is a major risk factor for the development and progression of kidney disease. Hydrogen sulfide (H2S) plays an important role in renal physiological and pathophysiological processes. However, whether H2S is able to mitigate kidney injury induced by obesity in mice remains unclear. In this study, we demonstrated that H2S significantly reduced the accumulation of lipids in the kidneys of high fat diet- (HFD-) induced obese mice. The results of hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining showed that H2S ameliorated the kidney structure, decreased the extent of interstitial injury, and reduced the degree of kidney fibrosis in HFD-induced obese mice. We found that H2S decreased the expression levels of tumor necrosis factor-α, interleukin- (IL-) 6, and monocyte chemoattractant protein-1 but increased the expression level of IL-10. Furthermore, H2S treatment decreased the protein expression of p50, p65, and p-p65 in the kidney of HFD-induced obese mice. In conclusion, H2S is able to mitigate renal injury in HFD-induced obese mice through the reduction of kidney inflammation by downregulating the expression of nuclear factor-kappa B. H2S or its releasing compounds may serve as a potential therapeutic molecule for obesity-induced kidney injury. 1. Introduction Obesity, well known as a major public health issue worldwide, has been reported to be associated with many diseases, such as hypertension and type 2 diabetes mellitus [1–3]. Accumulating evidence suggests that obesity is also a major risk factor for the development and progression of chronic kidney disease (CKD) [3–5]. Along with the development of obesity, fast body weight gain increases tubular sodium reabsorption in the kidney, which in turn leads to renal vasodilation and glomerular hyperfiltration and eventually results in an increased glomerular filtration rate. Excess body weight gain may raise blood pressure, which can lead to increased renal blood flow. Consequently, these hemodynamic changes cause an increase of glomerular size accompanied by mesangial matrix expansion and podocyte injury [6–8]. Both hemodynamic and morphological changes, together with other factors, such as renal inflammation [9, 10], oxidative stress [9, 11], lipotoxicity [12, 13], insulin resistance [14], and fibrosis [15, 16], may result in renal dysfunction and ultimately lead to end-stage renal disease (ESRD). Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule in mammalian tissues, which is enzymatically synthesized by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) [17–19]. All three enzymes are abundantly expressed in the kidney and are involved in renal H2S production [18, 20]. Accumulating evidence supports the roles of H2S in renal physiology and pathology [18–21]. Under physiological conditions, basal renal H2S regulates tubular functions and renal hemodynamics, including changes of renal blood flow, natriuresis, kaliuresis, glomerular filtration rate, and urinary excretion [18, 19, 22]. H2S can also act as an oxygen sensor in the renal medulla, where its accumulation in hypoxic conditions could restore oxygen balance by increasing medullary blood flow, reducing energy requirements for tubular transport, and directly inhibiting mitochondrial respiration [23, 24]. Because medullary hypoxia is a common pathologic feature of CKD, H2S deficiency may contribute to progression of CKD by limiting the important adaptive mechanism [23, 25]. Under pathological conditions, H2S plays a renoprotective role in the kidney. For instance, treatment with NaHS (a donor of H2S) could effectively attenuate ischemia/reperfusion-induced acute kidney injury by accelerating tubular cell proliferation and reducing superoxide formation and lipid peroxidation [26]. Importantly, the significant reduction of plasma H2S concentration and the downregulation of H2S-producing enzymes have been found in a rodent model of kidney injury and ESRD patients [23, 27]. H2S supplementation has been shown to reduce macrophage infiltration, glomerulosclerosis, and interstitial fibrosis as well as inhibit the blunt upregulation of adhesion molecules and inflammatory mediators [28]. Pla (...truncated)


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Dongdong Wu, Biao Gao, Mengling Li, Ling Yao, Shuaiwei Wang, Mingliang Chen, Hui Li, Chunyan Ma, Ailing Ji, Yanzhang Li. Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet-Induced Obese Mice, Oxidative Medicine and Cellular Longevity, 2016, 2016, DOI: 10.1155/2016/2715718