{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T12:10:30Z","timestamp":1767183030054,"version":"build-2238731810"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST-102-2320-B-003-001-MY3"],"award-info":[{"award-number":["MOST-102-2320-B-003-001-MY3"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Chronic kidney disease (CKD) progression may be evoked through dysregulated mitochondrial dynamics enhanced oxidative stress and inflammation contributing to high cardiovascular morbidity and mortality. Previous study has demonstrated sodium thiosulfate (STS, Na\n                    <jats:sub>2<\/jats:sub>\n                    S\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>3<\/jats:sub>\n                    ) could effectively attenuate renal oxidative injury in the animal model of renovascular hypertension. We explored whether the potentially therapeutic effect of STS is available on the attenuating CKD injury in thirty-six male Wistar rats with 5\/6 nephrectomy. We determined the STS effect on reactive oxygen species (ROS) amount in vitro and in vivo by an ultrasensitive chemiluminescence-amplification method, ED-1 mediated inflammation, Masson\u2019s trichrome stained fibrosis, mitochondrial dynamics (fission and fusion) and two types of programmed cell death, apoptosis and ferroptosis by western blot and immunohistochemistry. Our\n                    <jats:italic>in vitro<\/jats:italic>\n                    data showed STS displayed the strongest scavenging ROS activity at the dosage of 0.1 g. We applied STS at 0.1 g\/kg intraperitoneally 5 times\/week for 4 weeks to these CKD rats. CKD significantly enhanced the degree in arterial blood pressure, urinary protein, BUN, creatinine, blood and kidney ROS amount, leukocytes infiltration, renal 4-HNE expression, fibrosis, dynamin-related protein 1 (Drp1) mediated mitochondrial fission, Bax\/c-caspase 9\/c-caspase 3\/poly (ADP-ribose) polymerase (PARP) mediated apoptosis, iron overload\/ferroptosis and the decreased xCT\/GPX4 expression and OPA-1 mediated mitochondrial fusion. STS treatment significantly ameliorated oxidative stress, leukocyte infiltration, fibrosis, apoptosis and ferroptosis and improved mitochondrial dynamics and renal dysfunction in CKD rats. Our results suggest that STS as drug repurposing strategy could attenuate CKD injury through the action of anti-mitochondrial fission, anti-inflammation, anti-fibrosis, anti-apoptotic, and anti-ferroptotic mechanisms.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0277652","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T13:24:32Z","timestamp":1676553872000},"page":"e0277652","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sodium thiosulfate through preserving mitochondrial dynamics ameliorates oxidative stress induced renal apoptosis and ferroptosis in 5\/6 nephrectomized rats with chronic kidney diseases"],"prefix":"10.1371","volume":"18","author":[{"given":"Yu-Hsuan","family":"Cheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-An","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Ching","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Ping","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7580-7069","authenticated-orcid":true,"given":"Chiang-Ting","family":"Chien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"pone.0277652.ref001","doi-asserted-by":"crossref","first-page":"S173","DOI":"10.1097\/01.ASN.0000070079.54912.B6","article-title":"Anemia management and the delay of chronic renal failure progression","volume":"14","author":"JB Rossert","year":"2003","journal-title":"J Am Soc Nephrol"},{"key":"pone.0277652.ref002","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0140-6736(05)17789-7","article-title":"Chronic kidney disease: the global challenge","volume":"365","author":"Nahas El","year":"2005","journal-title":"Lancet"},{"key":"pone.0277652.ref003","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1046\/j.1523-1755.2003.00118.x","article-title":"Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced water","volume":"64","author":"KC Huang","year":"2003","journal-title":"Kidney Int"},{"key":"pone.0277652.ref004","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/sj.ki.5001576","article-title":"Electrolyzed-reduced water reduced hemodialysis-induced erythrocyte impairment in end-stage renal disease patients","volume":"70","author":"KC Huang","year":"2006","journal-title":"Kidney Int"},{"key":"pone.0277652.ref005","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1093\/ndt\/gfq082","article-title":"Electrolysed-reduced water dialysate improves T-cell damage in end-stage renal disease patients with chronic haemodialysis","volume":"25","author":"KC Huang","year":"2010","journal-title":"Nephrol Dial Transplant"},{"key":"pone.0277652.ref006","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1160\/th14-03-0258","article-title":"Glucagon-like peptide-1 receptor agonist activation ameliorates venous thrombosis-induced arteriovenous fistula failure in chronic kidney disease","volume":"112","author":"CT Chien","year":"2014","journal-title":"Thromb Haemost"},{"key":"pone.0277652.ref007","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1681\/ASN.V125973","article-title":"De novo demonstration and co-localization of free-radical production and apoptosis formation in rat kidney subjected to ischemia\/reperfusion","volume":"12","author":"CT Chien","year":"2001","journal-title":"J Am Soc Nephrol"},{"key":"pone.0277652.ref008","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/toxsci\/kfu121","article-title":"Sialic acid rescues repurified lipopolysaccharide-induced acute renal failure via inhibiting TLR4\/PKC\/gp91-mediated endoplasmic reticulum stress, apoptosis, autophagy, and pyroptosis signaling","volume":"141","author":"CC Yang","year":"2014","journal-title":"Toxicol Sci"},{"key":"pone.0277652.ref009","first-page":"5080843","article-title":"Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis","volume":"2019","author":"LJ Su","year":"2019","journal-title":"Oxid Med Cell Longev"},{"issue":"7","key":"pone.0277652.ref010","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.tibs.2020.03.009","article-title":"Reciprocal regulation of mitochondrial fission and fusion","volume":"45","author":"R Sabouny","year":"2020","journal-title":"Trends in Biochemical Sciences"},{"key":"pone.0277652.ref011","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.2215\/CJN.10241110","article-title":"Sodium thiosulfate pharmacokinetics in hemodialysis patients and healthy volunteers","volume":"6","author":"S Farese","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"pone.0277652.ref012","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1525-139X.2010.00738.x","article-title":"Sodium thiosulfate: new hope for the treatment of calciphylaxis","volume":"23","author":"MR Hayden","year":"2010","journal-title":"Semin Dial"},{"issue":"1","key":"pone.0277652.ref013","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000510047","article-title":"Sodium Thiosulfate Ameliorates Renovascular Hypertension-Induced Renal Dysfunction and Injury in Rats","volume":"46","author":"PL Chou","year":"2021","journal-title":"Kidney Blood Press Res"},{"key":"pone.0277652.ref014","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ajem.2009.09.014","article-title":"Acute cyanide poisoning among jewelry and textile industry workers","volume":"29","author":"L Coentrao","year":"2011","journal-title":"Am J Emerg Med"},{"key":"pone.0277652.ref015","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1039\/c2mt20076g","article-title":"The effect of sodium thiosulfate on the metabolism of cis-platin in human plasma in vitro","volume":"4","author":"M Sooriyaarachchi","year":"2012","journal-title":"Metallomics"},{"key":"pone.0277652.ref016","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1161\/hs0202.103410","article-title":"Safety of intraventricular sodium nitroprusside and thiosulfate for the treatment of cerebral vasospasm in the intensive care unit setting","volume":"33","author":"JE Thomas","year":"2002","journal-title":"Stroke"},{"key":"pone.0277652.ref017","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.niox.2014.10.002","article-title":"Sodium thiosulfate attenuates angiotensin II-induced hypertension, proteinuria and renal damage","volume":"42","author":"PM Snijder","year":"2014","journal-title":"Nitric Oxide"},{"key":"pone.0277652.ref018","doi-asserted-by":"crossref","first-page":"e0124881","DOI":"10.1371\/journal.pone.0124881","article-title":"Sodium thiosulfate ameliorates oxidative stress and preserves renal function in hyperoxaluric rats","volume":"10","author":"RK Bijarnia","year":"2015","journal-title":"PLoS One"},{"key":"pone.0277652.ref019","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1161\/01.ATV.15.2.190","article-title":"The Effect of \u03b1-tocopherol supplementation on LDL oxidation. A dose-response study. Arterioscler","volume":"15","author":"I Jialal","year":"1995","journal-title":"Thrombosis Vasc. Biol"},{"issue":"2","key":"pone.0277652.ref020","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.cardiores.2003.11.024","article-title":"Interactions between the sympathetic nervous system and the kidneys in arterial hypertension","volume":"61","author":"O Grisk","year":"2004","journal-title":"Cardiovasc. Res"},{"issue":"2014","key":"pone.0277652.ref021","doi-asserted-by":"crossref","first-page":"F418","DOI":"10.1152\/ajprenal.00014.2014","article-title":"Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease","volume":"307","author":"CR Martens","year":"2014","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"pone.0277652.ref022","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1001\/jamadermatol.2013.4565","article-title":"Intralesional sodium thiosulfate for the treatment of calciphylaxis","volume":"149","author":"L Strazzula","year":"2013","journal-title":"JAMA Dermatol"},{"key":"pone.0277652.ref023","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1056\/NEJMc1809501","article-title":"Sodium thiosulfate and cisplatin-induced hearing loss","volume":"379","author":"DR Freyer","year":"2018","journal-title":"N Engl J Med"},{"key":"pone.0277652.ref024","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/nep.13081","article-title":"Systematic review of sodium thiosulfate in treating calciphylaxis in chronic kidney disease patients","volume":"23","author":"T Peng","year":"2018","journal-title":"Nephrology (Carlton)"},{"key":"pone.0277652.ref025","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1525-139X.2011.00848.x","article-title":"Unexpectedly severe metabolic acidosis associated with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathy","volume":"24","author":"N Selk","year":"2011","journal-title":"Semin Dial"},{"key":"pone.0277652.ref026","doi-asserted-by":"crossref","first-page":"220","DOI":"10.3747\/pdi.2011.00088","article-title":"Chemical peritonitis after intraperitoneal sodium thiosulfate","volume":"32","author":"DR Gupta","year":"2012","journal-title":"Perit Dialysis Int J Int Soc Perit Dial"},{"key":"pone.0277652.ref027","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cbi.2017.07.002","article-title":"Sodium thiosulfate post-conditioning protects rat hearts against ischemia reperfusion injury via reduction of apoptosis and oxidative stress","volume":"274","author":"S Ravindran","year":"2017","journal-title":"Chem Biol Interact"},{"key":"pone.0277652.ref028","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s10557-017-6751-0","article-title":"Sodium Thiosulfate preconditioning ameliorates ischemia\/reperfusion injury in rat hearts via reduction of oxidative stress and apoptosis","volume":"31","author":"S Ravindran","year":"2017","journal-title":"Cardiovasc Drugs Ther"},{"key":"pone.0277652.ref029","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1089\/ars.2013.5354","article-title":"Cystathionine \u03b3-lyase deficiency protects mice from galactosamine\/lipopolysaccharide-induced acute liver failure","volume":"20","author":"K Shirozu","year":"2014","journal-title":"Antioxid Redox Signal"},{"key":"pone.0277652.ref030","doi-asserted-by":"crossref","first-page":"650968","DOI":"10.3389\/fphar.2021.650968","article-title":"Cardiac Protection by Oral Sodium Thiosulfate in a Rat Model of L-NNA-Induced Heart Disease","volume":"12","author":"ITN Nguyen","year":"2021","journal-title":"Front Pharmacol"},{"key":"pone.0277652.ref031","first-page":"41","article-title":"Lung changes in rats under the action of paraquat and the importance of antioxidants","volume":"9","author":"VP Novoselova","year":"1989","journal-title":"Probl Tuberk"},{"key":"pone.0277652.ref032","doi-asserted-by":"crossref","first-page":"258","DOI":"10.2215\/CJN.03250906","article-title":"Nephrogenic systemic fibrosis: A mysterious disease in patients with renal failure\u2014Role of gadolinium-based contrast media in causation and the beneficial effect of IV sodium thiosulfate","volume":"2","author":"P Yerram","year":"2007","journal-title":"Clin J Am Soc Nephrol"},{"key":"pone.0277652.ref033","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/978-981-13-8871-2_29","article-title":"Oxidative Stress and Renal Fibrosis: Mechanisms and Therapies","volume":"1165","author":"H Su","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"pone.0277652.ref034","doi-asserted-by":"crossref","first-page":"153947","DOI":"10.1016\/j.phymed.2022.153947","article-title":"Shen Shuai \u2161 Recipe attenuates renal fibrosis in chronic kidney disease by improving hypoxia-induced the imbalance of mitochondrial dynamics via PGC-1\u03b1 activation","volume":"98","author":"M Wang","year":"2022","journal-title":"Phytomedicine"},{"issue":"3","key":"pone.0277652.ref035","doi-asserted-by":"crossref","first-page":"405","DOI":"10.33549\/physiolres.934392","article-title":"Contribution of selected vasoactive systems to blood pressure regulation in two models of chronic kidney disease","volume":"69","author":"N Dr\u00e1bkov\u00e1","year":"2020","journal-title":"Physiol Res"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0295162","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"record-id":"49740"},{"DOI":"10.1371\/journal.pone.0295162","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0277652","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T13:53:46Z","timestamp":1701179626000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0277652"}},"subtitle":[],"editor":[{"given":"Hiroyasu","family":"Nakano","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,2,16]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0277652","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,16]]}}}