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 |
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| Authors: | Mohammad Khabbaz Shirazi Asaad Azarnezhad Mohammad Foad Abazari Mansour Poorebrahim Pegah Ghoraeian Nima Sanadgol Hanieh Bokharaie Sahar Heydari Amin Abbasi Sahra Kabiri Maryam Nouri Aleagha Seyed Ehsan Enderami Amir Savar Dashtaki Hassan Askari |
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| Affiliation: | 1. Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;2. Cellular and Molecular Research Center, Kurdistan niversity of Medical Sciences, Sanandaj, Iran;3. Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran;4. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran;6. Department of Genetics, Islamic Azad University, Tehran Medical Branch, Tehran, Iran;7. Department of genetic, Biology Research Center, Zanjan Branch, Islamic Azad University, Zanjan, Iran;8. Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran;9. Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran;10. Stem Cell Technology Research Center, Tehran, Iran;11. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran;12. Cardiac Surgery and Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran |
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| Abstract: | The interplay between H2S 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 2S, (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 2S 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. |
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| Keywords: | autophagy chronic kidney disease (CKD) hydrogen sulfide nitric oxide (NO) oxidative stress |
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