The Role of Nitric Oxide Signaling in Renoprotective Effects of Hydrogen Sulfide Against Chronic Kidney Disease in Rats: Involvement of Oxidative Stress, Autophagy and Apoptosis Publisher Pubmed



Shirazi MK¹ ; Azarnezhad A² ; Abazari MF³ ; Poorebrahim M⁴ ; Ghoraeian P³ ; Sanadgol N⁵ ; Bokharaie H⁶ ; Heydari S⁷ ; Abbasi A⁸ ; Kabiri S⁹ ; Aleagha MN³ ; Enderami SE¹⁰ ; Dashtaki AS¹¹ ; Askari H¹²
Source: Journal of Cellular Physiology Published:2019

Abstract

The interplay between H 2 S and nitric oxide (NO) is thought to contribute to renal functions. The current study was designed to assess the role of NO in mediating the renoprotective effects of hydrogen sulfide in the 5/6 nephrectomy (5/6 Nx) animal model. Forty rats were randomly assigned to 5 experimental groups: (a) Sham; (b) 5/6 Nx; (c) 5/6Nx+sodium hydrosulfide-a donor of H 2 S, (5/6Nx+sodium hydrosulfide [NaHS]); (d) 5/6Nx+NaHS+ L-NAME (a nonspecific nitric oxide synthase [NOS] inhibitor); (e) 5/6Nx+NaHS+aminoguanidine (a selective inhibitor of inducible NOS [iNOS]). Twelve weeks after 5/6 Nx, we assessed the expressions of iNOS and endothelial NOS (eNOS), oxidative/antioxidant status, renal fibrosis, urine N-acetyl-b-glucosaminidase (NAG) activity as the markers of kidney injury and various markers of apoptosis, inflammation, remodeling, and autophagy. NaHS treatment protected the animals against chronic kidney injury as depicted by improved oxidative/antioxidant status, reduced apoptosis, and autophagy and attenuated messenger RNA (mRNA) expression of genes associated with inflammation, remodeling, and NAG activity. Eight weeks Nω-nitro-l-arginine methyl ester (L-NAME) administration reduced the protective effects of hydrogen sulfide. In contrast, aminoguanidine augmented the beneficial effects of hydrogen sulfide. Our finding revealed some fascinating interactions between NO and H 2 S in the kidney. Moreover, the study suggests that NO, in an isoform-dependent manner, can exert renoprotective effects in 5/6 Nx model of CKD. © 2018 Wiley Periodicals, Inc.