title: Hydrogen sulfide alleviates diabetic nephropathy in a streptozotocin-induced diabetic rat model.
abstract: Accumulating evidence has demonstrated that hydrogen sulfide (H2S) plays critical roles in the pathogenesis of chronic kidney diseases. This study was designed to investigate whether H2S has protective effects against diabetic nephropathy. Diabetic rats were induced by intraperitoneal injection of streptozotocin and administrated with H2S donor NaHS for 12 weeks. Rat glomerular mesangial cells were pretreated with NaHS or MAPK inhibitors (U0126, SP600125, and SB203580) prior to high glucose exposure, and cell proliferation was determined. Our findings suggest that H2S can improve renal function and attenuate glomerular basement membrane thickening, mesangial matrix deposition, and renal interstitial fibrosis in diabetic rats. H2S was found to reduce high glucose-induced oxidative stress by activating the Nrf2 antioxidant pathway and to exert anti-inflammatory effects by inhibiting NF-κB signaling. In addition, H2S reduced high glucose-induced mesangial cell proliferation by blockade of MAPK signaling pathways. Moreover, H2S was also found to inhibit the renin-angiotensin system in diabetic kidney. In conclusion, our study demonstrates that H2S alleviates the development of diabetic nephropathy by attenuating oxidative stress and inflammation, reducing mesangial cell proliferation, and inhibiting renin-angiotensin system activity.
authors.affiliation: From the Departments of Cardiology, zhou-xiang@suda.edu.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Endocrinology, and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Nephrology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Zhoubing
authors.initials: Z
authors.lastname: Zhan
authors.affiliation: From the Departments of Cardiology.
authors.forename: Jianchang
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005355:Fibrosis; D005920:Glomerular Mesangium / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000737:chemistry*; D007249:Inflammation; D007668:Kidney / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy; D012084:Renin-Angiotensin System; D013311:Streptozocin
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013311:Streptozocin; D006862:Hydrogen Sulfide
keywords: Diabetes; Diabetic Nephropathy; Hydrogen Sulfide; Inflammation; Mesangial Cell Proliferation; Oxidative Stress; Renin-Angiotensin System