{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:26:42Z","timestamp":1792805202285,"version":"4.5.0"},"reference-count":75,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education of Singapore Tier 2 Research grant","award":["MOE2017-T2-2-029"],"award-info":[{"award-number":["MOE2017-T2-2-029"]}],"id":[{"id":"https:\/\/ror.org\/01kcva023","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Jiangsu Nature Science Foundation","award":["BK20181185"],"award-info":[{"award-number":["BK20181185"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cisplatin, a widely used chemotherapy for the treatment of various tumors, is clinically limited due to its extensive nephrotoxicity. Inflammatory response in tubular cells is a driving force for cisplatin-induced nephrotoxicity. The plant-derived agents are widely used to relieve cisplatin-induced renal dysfunction in preclinical studies. Polysulfide and hydrogen sulfide (H2S) are ubiquitously expressed in garlic, and both of them are documented as potential agents for preventing and treating inflammatory disorders. This study was designed to determine whether polysulfide and H2S could attenuate cisplatin nephrotoxicity through suppression of inflammatory factors. In renal proximal tubular cells, we found that sodium tetrasulfide (Na2S4), a polysulfide donor, and sodium hydrosulfide (NaHS) and GYY4137, two H2S donors, ameliorated cisplatin-caused renal toxicity through suppression of the massive production of inflammatory cytokines, including tumor necrosis factor \u03b1 (TNF-\u03b1), interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Mechanistically, the anti-inflammatory actions of Na2S4 and H2S may be mediated by persulfidation of signal transducer and activator of transcription 3 (STAT3) and inhibitor kappa B kinase \u03b2 (IKK\u03b2), followed by decreased phosphorylation of STAT3 and IKK\u03b2. Moreover, the nuclear translocation of nuclear transcription factor kappa B (NF-\u03baB), and phosphorylation and degradation of nuclear factor kappa B inhibitor protein alpha (I\u03baB\u03b1) induced by cisplatin, were also mitigated by both polysulfide and H2S. In mice, after treatment with polysulfide and H2S donors, cisplatin-associated renal dysfunction was strikingly ameliorated, as evidenced by measurement of serum blood urea nitrogen (BUN) and creatinine levels, renal morphology, and the expression of renal inflammatory factors. Our present work suggests that polysulfide and H2S could afford protection against cisplatin nephrotoxicity, possibly via persulfidating STAT3 and IKK\u03b2 and inhibiting NF-\u03baB-mediated inflammatory cascade. Our results might shed light on the potential benefits of garlic-derived polysulfide and H2S in chemotherapy-induced renal damage.<\/jats:p>","DOI":"10.3390\/ijms21207805","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T10:27:58Z","timestamp":1603362478000},"page":"7805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Polysulfide and Hydrogen Sulfide Ameliorate Cisplatin-Induced Nephrotoxicity and Renal Inflammation through Persulfidating STAT3 and IKK\u03b2"],"prefix":"10.3390","volume":"21","author":[{"given":"Hai-Jian","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7909-6388","authenticated-orcid":false,"given":"Bin","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Yuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Song","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"},{"name":"National University of Singapore (Suzhou) Research Institute, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.tips.2019.03.003","article-title":"Rethinking Alkylating(-Like) Agents for Solid Tumor Management","volume":"40","author":"Lajous","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.3390\/cancers3011351","article-title":"Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects","volume":"3","author":"Florea","year":"2011","journal-title":"Cancers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/S0272-6386(86)80112-3","article-title":"Nephrotoxicity Induced by Cancer Chemotherapy With Special Emphasis on Cisplatin Toxicity","volume":"8","author":"Ries","year":"1986","journal-title":"Am. J. Kidney Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrd1691","article-title":"Cellular processing of platinum anticancer drugs","volume":"4","author":"Wang","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/sj.ki.5002786","article-title":"Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies","volume":"73","author":"Pabla","year":"2008","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"F505","DOI":"10.1152\/ajprenal.90545.2008","article-title":"The copper transporter Ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity","volume":"296","author":"Pabla","year":"2009","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Holditch, S.J., Brown, C.N., Lombardi, A.M., Nguyen, K.N., and Edelstein, C.L. (2019). Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123011"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/ki.2013.330","article-title":"Pharmacological activation of NQO1 increases NAD+ levels and attenuates cisplatin-mediated acute kidney injury in mice","volume":"85","author":"Oh","year":"2014","journal-title":"Kidney Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/967826","article-title":"Pathophysiology of Cisplatin-Induced Acute Kidney Injury","volume":"2014","author":"Ozkok","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/4320374","article-title":"Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity","volume":"2016","author":"Ojha","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.biopha.2018.12.010","article-title":"Phytochemicals: Current strategy to sensitize cancer cells to cisplatin","volume":"110","author":"Sun","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1089\/jmf.2008.0033","article-title":"Garlic Powder Ameliorates Cisplatin-Induced Nephrotoxicity and Oxidative Stress","volume":"11","author":"Chirino","year":"2008","journal-title":"J. Med. Food"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"136338","DOI":"10.1016\/j.scitotenv.2019.136338","article-title":"Impact of garlic (Allium sativum) oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats","volume":"710","author":"Dessouki","year":"2020","journal-title":"Sci. Total. Environ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.niox.2014.02.006","article-title":"Hydrogen sulfide and the liver","volume":"41","author":"Mani","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rodrigues, C., and Percival, S.S. (2019). Immunomodulatory Effects of Glutathione, Garlic Derivatives, and Hydrogen Sulfide. Nutrients, 11.","DOI":"10.3390\/nu11020295"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.fct.2016.07.016","article-title":"Garlic-derived natural polysulfanes as hydrogen sulfide donors: Friend or foe?","volume":"95","author":"Yagdi","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.redox.2018.01.012","article-title":"Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity","volume":"15","author":"Cao","year":"2018","journal-title":"Redox Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cao, X., Zhang, W., Moore, P.K., and Bian, J.S. (2019). Protective Smell of Hydrogen Sulfide and Polysulfide in Cisplatin-Induced Nephrotoxicity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020313"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/ars.2017.7157","article-title":"Renal Protective Effect of Hydrogen Sulfide in Cisplatin-Induced Nephrotoxicity","volume":"29","author":"Cao","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108647","DOI":"10.1016\/j.biopha.2019.108647","article-title":"Renoprotective effect of scutellarin on cisplatin-induced renal injury in mice: Impact on inflammation, apoptosis, and autophagy","volume":"112","author":"Sun","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.intimp.2015.06.020","article-title":"Saikosaponin-D reduces cisplatin-induced nephrotoxicity by repressing ROS-mediated activation of MAPK and NF-\u03baB signalling pathways","volume":"28","author":"Ma","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.bbi.2018.07.005","article-title":"Hydrogen sulfide inhibits ATP-induced neuroinflammation and A\u03b21\u201342 synthesis by suppressing the activation of STAT3 and cathepsin S","volume":"73","author":"Cao","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1042\/CS20190514","article-title":"Endogenous hydrogen sulfide sulfhydrates IKK\u03b2 at cysteine 179 to control pulmonary artery endothelial cell inflammation","volume":"133","author":"Zhang","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1089\/ars.2017.7076","article-title":"Hydrogen Sulfide and Polysulfide Signaling","volume":"27","author":"Kimura","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4202","DOI":"10.3390\/ijms20174202","article-title":"Hydrogen Sulfide Prevents Elastin Loss and Attenuates Calcification Induced by High Glucose in Smooth Muscle Cells through Suppression of Stat3\/Cathepsin S Signaling Pathway","volume":"20","author":"Zhou","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"172422","DOI":"10.1016\/j.ejphar.2019.172422","article-title":"Tetramethylpyrazine guards against cisplatin-induced nephrotoxicity in rats through inhibiting HMGB1\/TLR4\/NF-\u03baB and activating Nrf2 and PPAR-\u03b3 signaling pathways","volume":"857","author":"Michel","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-019-0518-9","article-title":"Molecular mechanisms of cisplatin-induced nephrotoxicity: A balance on the knife edge between renoprotection and tumor toxicity","volume":"26","author":"Volarevic","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ebiom.2018.09.031","article-title":"Celastrol ameliorates cisplatin nephrotoxicity by inhibiting NF-kappaB and improving mitochondrial function","volume":"36","author":"Yu","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101411","DOI":"10.1016\/j.redox.2019.101411","article-title":"Salusin-beta mediates tubular cell apoptosis in acute kidney injury: Involvement of the PKC\/ROS signaling pathway","volume":"30","author":"Lu","year":"2020","journal-title":"Redox Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.tips.2018.03.009","article-title":"Garlic and Gaseous Mediators","volume":"39","author":"Rose","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1016\/j.foodchem.2016.10.076","article-title":"Boiling enriches the linear polysulfides and the hydrogen sulfide-releasing activity of garlic","volume":"221","author":"Tocmo","year":"2017","journal-title":"Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/cr.2010.183","article-title":"NF-\u03baB and STAT3\u2013key players in liver inflammation and cancer","volume":"21","author":"He","year":"2010","journal-title":"Cell Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s40620-017-0392-z","article-title":"Cisplatin nephrotoxicity: A review of the literature","volume":"31","author":"Manohar","year":"2017","journal-title":"J. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.3390\/toxins2112490","article-title":"Mechanisms of Cisplatin Nephrotoxicity","volume":"2","author":"Miller","year":"2010","journal-title":"Toxins"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.intimp.2017.06.011","article-title":"RETRACTED: Diallyl trisulfide, a garlic polysulfide protects against As-induced renal oxidative nephrotoxicity, apoptosis and inflammation in rats by activating the Nrf2\/ARE signaling pathway","volume":"50","author":"Miltonprabu","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.pharep.2015.01.005","article-title":"Hydrogen sulfide in pharmacology and medicine\u2013An update","volume":"67","year":"2015","journal-title":"Pharmacol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/5350161","article-title":"Total Coumarins fromHydrangea paniculataProtect against Cisplatin-Induced Acute Kidney Damage in Mice by Suppressing Renal Inflammation and Apoptosis","volume":"2017","author":"Sen","year":"2017","journal-title":"Evidence-Based Complement. Altern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Probst, B.L., McCauley, L., Trevino, I., Wigley, W.C., and Ferguson, D.A. (2015). Cancer Cell Growth Is Differentially Affected by Constitutive Activation of NRF2 by KEAP1 Deletion and Pharmacological Activation of NRF2 by the Synthetic Triterpenoid, RTA 405. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135257"},{"key":"ref_39","first-page":"3098","article-title":"IKK phosphorylation of NF-\u03baB at serine 536 contributes to acquired cisplatin resistance in head and neck squamous cell cancer","volume":"5","author":"Li","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0092-8674(01)00495-0","article-title":"Nitrosylation. The prototypic redox-based signaling mechanism","volume":"106","author":"Stamler","year":"2001","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1089\/ars.2013.5223","article-title":"STAT3 Regulation by S-Nitrosylation: Implication for Inflammatory Disease","volume":"20","author":"Kim","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8945","DOI":"10.1073\/pnas.0400588101","article-title":"Nitric oxide represses inhibitory \u03baB kinase through S-nitrosylation","volume":"101","author":"Reynaert","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"599","DOI":"10.2174\/138945010791011938","article-title":"NF-kappaB signaling: Multiple angles to target OA","volume":"11","author":"Marcu","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1007\/s00228-013-1568-7","article-title":"Signalling mechanisms involved in renal pathological changes during cisplatin-induced nephropathy","volume":"69","author":"Jaiman","year":"2013","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1600-065X.2011.01088.x","article-title":"The noncanonical NF-\u03baB pathway","volume":"246","author":"Sun","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1600-065X.2012.01098.x","article-title":"Regulation of NF-\u03baB by ubiquitination and degradation of the I\u03baBs","volume":"246","author":"Kanarek","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zhu, P., Wang, Y., Wei, Z., Tao, L., Zhu, Z., Sheng, X., Wang, S., Ruan, J., and Liu, Z. (2015). Antimetastatic Therapies of the Polysulfide Diallyl Trisulfide against Triple-Negative Breast Cancer (TNBC) via Suppressing MMP2\/9 by Blocking NF-\u03baB and ERK\/MAPK Signaling Pathways. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123781"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41598-017-00557-2","article-title":"Hydrogen sulfide ameliorates chronic renal failure in rats by inhibiting apoptosis and inflammation through ROS\/MAPK and NF-\u03baB signaling pathways","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/7432845","article-title":"A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice","volume":"2016","author":"Liu","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_50","first-page":"337","article-title":"Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors","volume":"230","author":"Whiteman","year":"2015","journal-title":"Bile Acids Their Recept."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1016\/j.juro.2016.05.029","article-title":"GYY4137, a Slow-Releasing Hydrogen Sulfide Donor, Ameliorates Renal Damage Associated with Chronic Obstructive Uropathy","volume":"196","author":"Lin","year":"2016","journal-title":"J. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/691070","article-title":"Hydrogen Sulfide Donor GYY4137 Protects against Myocardial Fibrosis","volume":"2015","author":"Meng","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_53","first-page":"493","article-title":"Effect of synthesized GYY4137, a slowly releasing hydrogen sulfide donor, on cell viability and distribution of hydrogen sulfide in mice","volume":"42","author":"Yu","year":"2010","journal-title":"Beijing Da Xue Xue Bao. Yi Xue Ban J. Peking Univ. Health Sci."},{"key":"ref_54","first-page":"121","article-title":"Hydrogen sulfide ameliorates the kidney dysfunction and damage in cisplatin-induced nephrotoxicity in rat","volume":"5","author":"Ahangarpour","year":"2014","journal-title":"Vet. Res. Forum Int. Q. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"150","DOI":"10.15171\/jnp.2017.26","article-title":"Sodium hydrogen sulfide (NaHS) ameliorates alterations caused by cisplatin in filtration slit diaphragm and podocyte cytoskeletal in rat kidney","volume":"6","author":"Karimi","year":"2017","journal-title":"J. Nephropathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1089\/ars.2019.7728","article-title":"S-Sulfhydration of SIRT3 by Hydrogen Sulfide Attenuates Mitochondrial Dysfunction in Cisplatin-Induced Acute Kidney Injury","volume":"31","author":"Yuan","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/ndt\/gfq447","article-title":"Inhibition of hydrogen sulphide formation reduces cisplatin-induced renal damage","volume":"26","author":"Francescato","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"925","DOI":"10.3109\/0886022X.2014.900599","article-title":"Protective effect of hydrogen sulfide on gentamicin-induced renal injury","volume":"36","author":"Otunctemur","year":"2014","journal-title":"Ren. Fail."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1124\/jpet.105.087601","article-title":"Protection against Cisplatin-Induced Toxicities by N-Acetylcysteine and Sodium Thiosulfate as Assessed at the Molecular, Cellular, and in Vivo Levels","volume":"314","author":"Dickey","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.niox.2016.04.005","article-title":"Hydrogen sulfide: A novel nephroprotectant against cisplatin-induced renal toxicity","volume":"57","author":"Dugbartey","year":"2016","journal-title":"Nitric Oxide"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/labinvest.2008.73","article-title":"Generation of endogenous hydrogen sulfide by cystathionine gamma-lyase limits renal ischemia\/reperfusion injury and dysfunction","volume":"88","author":"Tripatara","year":"2008","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"F27","DOI":"10.1152\/ajprenal.00096.2009","article-title":"Ischemia-reperfusion reduces cystathionine-beta-synthase-mediated hydrogen sulfide generation in the kidney. American journal of physiology","volume":"297","author":"Xu","year":"2009","journal-title":"Renal Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1113\/expphysiol.2011.059725","article-title":"Cytoprotective actions of hydrogen sulfide in ischaemia-reperfusion injury","volume":"96","author":"King","year":"2011","journal-title":"Exp. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ejphar.2009.01.041","article-title":"Characterisation of cystathionine gamma-lyase\/hydrogen sulphide pathway in ischaemia\/reperfusion injury of the mouse kidney: An in vivo study","volume":"606","author":"Tripatara","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/ki.2013.449","article-title":"Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy","volume":"85","author":"Song","year":"2014","journal-title":"Kidney Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"111779","DOI":"10.1016\/j.yexcr.2019.111779","article-title":"H2S alleviates renal injury and fibrosis in response to unilateral ureteral obstruction by regulating macrophage infiltration via inhibition of NLRP3 signaling","volume":"387","author":"Zhou","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1016\/j.bbadis.2013.06.015","article-title":"Involvement of hydrogen sulfide and homocysteine transsulfuration pathway in the progression of kidney fibrosis after ureteral obstruction","volume":"1832","author":"Jung","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"28827","DOI":"10.1074\/jbc.M114.596593","article-title":"Hydrogen Sulfide Alleviates Diabetic Nephropathy in a Streptozotocin-induced Diabetic Rat Model","volume":"289","author":"Zhou","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1093\/ndt\/gfq749","article-title":"Rescue of mesangial cells from high glucose-induced over-proliferation and extracellular matrix secretion by hydrogen sulfide","volume":"26","author":"Yuan","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"F1354","DOI":"10.1152\/ajprenal.00301.2006","article-title":"Detrimental role of homocysteine in renal ischemia-reperfusion injury","volume":"292","author":"Prathapasinghe","year":"2007","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"F912","DOI":"10.1152\/ajprenal.00040.2008","article-title":"Inhibition of cystathionine-beta-synthase activity during renal ischemia-reperfusion: Role of pH and nitric oxide. American journal of physiology","volume":"295","author":"Prathapasinghe","year":"2008","journal-title":"Renal Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1161\/CIRCULATIONAHA.107.753467","article-title":"Characterization of a Novel, Water-Soluble Hydrogen Sulfide\u2013Releasing Molecule (GYY4137)","volume":"117","author":"Li","year":"2008","journal-title":"Circulation"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.3390\/ijms18061097","article-title":"C1q\/TNF-Related Protein-9 Ameliorates Ox-LDL-Induced Endothelial Dysfunction via PGC-1alpha\/AMPK-Mediated Antioxidant Enzyme Induction","volume":"18","author":"Sun","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1159\/000478920","article-title":"Interactions of TLR4 and PPAR\u03b3, Dependent on AMPK Signalling Pathway Contribute to Anti-Inflammatory Effects of Vaccariae Hypaphorine in Endothelial Cells","volume":"42","author":"Sun","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_75","first-page":"7007","article-title":"Diosmetin Attenuates Akt Signaling Pathway by Modulating Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-kappaB)\/Inducible Nitric Oxide Synthase (iNOS) in Streptozotocin (STZ)-Induced Diabetic Nephropathy Mice","volume":"24","author":"Jiang","year":"2018","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7805\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:25:41Z","timestamp":1760178341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,21]]},"references-count":75,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21207805"],"URL":"https:\/\/doi.org\/10.3390\/ijms21207805","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,21]]}}}