{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T18:26:15Z","timestamp":1776536775258,"version":"3.51.2"},"reference-count":61,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p>Elevated level of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), is associated with end-stage renal diseases. Hcy metabolizes in the body to produce hydrogen sulfide (H<jats:sub>2<\/jats:sub>S), and studies have demonstrated a protective role of H<jats:sub>2<\/jats:sub>S in end-stage organ failure. However, the role of H<jats:sub>2<\/jats:sub>S in HHcy-associated renal diseases is unclear. The present study was aimed to determine the role of H<jats:sub>2<\/jats:sub>S in HHcy-associated renal damage. Cystathionine-\u03b2-synthase heterozygous (CBS+\/\u2212) and wild-type (WT, C57BL\/6J) mice with two kidney (2-K) were used in this study and supplemented with or without NaHS (30 \u03bcmol\/l, H<jats:sub>2<\/jats:sub>S donor) in the drinking water. To expedite the HHcy-associated glomerular damage, uninephrectomized (1-K) CBS(+\/\u2212) and 1-K WT mice were also used with or without NaHS supplementation. Plasma Hcy levels were elevated in CBS(+\/\u2212) 2-K and 1-K and WT 1-K mice along with increased proteinuria, whereas, plasma levels of H<jats:sub>2<\/jats:sub>S were attenuated in these groups compared with WT 2-K mice. Interestingly, H<jats:sub>2<\/jats:sub>S supplementation increased plasma H<jats:sub>2<\/jats:sub>S level and normalized the urinary protein secretion in the similar groups of animals as above. Increased activity of matrix metalloproteinase (MMP)-2 and -9 and apoptotic cells were observed in the renal cortical tissues of CBS(+\/\u2212) 2-K and 1-K and WT 1-K mice; however, H<jats:sub>2<\/jats:sub>S prevented apoptotic cell death and normalized increased MMP activities. Increased expression of desmin and downregulation of nephrin in the cortical tissue of CBS(+\/\u2212) 2-K and 1-K and WT 1-K mice were ameliorated with H<jats:sub>2<\/jats:sub>S supplementation. Additionally, in the kidney tissues of CBS(+\/\u2212) 2-K and 1-K and WT 1-K mice, increased superoxide (O<jats:sub>2<\/jats:sub><jats:sup>\u2022\u2212<\/jats:sup>) production and reduced glutathione (GSH)-to-oxidized glutathione (GSSG) ratio were normalized with exogenous H<jats:sub>2<\/jats:sub>S supplementation. These results demonstrate that HHcy-associated renal damage is related to decreased endogenous H<jats:sub>2<\/jats:sub>S generation in the body. Additionally, here we demonstrate with evidence that H<jats:sub>2<\/jats:sub>S supplementation prevents HHcy-associated renal damage, in part, through its antioxidant properties.<\/jats:p>","DOI":"10.1152\/ajprenal.00145.2009","type":"journal-article","created":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T01:48:02Z","timestamp":1243475282000},"page":"F410-F419","source":"Crossref","is-referenced-by-count":130,"title":["Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure"],"prefix":"10.1152","volume":"297","author":[{"given":"Utpal","family":"Sen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poulami","family":"Basu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oluwasegun A.","family":"Abe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srikanth","family":"Givvimani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neetu","family":"Tyagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naira","family":"Metreveli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karan S.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Passmore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh C.","family":"Tyagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-03-01066.1996"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401451"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/129.5.928"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2005.10.007"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-007-0011-8"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199104253241701"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.278.1.F122"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-02-005991"},{"key":"R10","unstructured":"Doeller JE, Grieshaber MK, Kraus DW.Chemolithoheterotrophy in a metazoan tissue: thiosulfate production matches ATP demand in ciliated mussel gills.J Exp Biol204: 3755\u20133764, 2001."},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2005.03.024"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-09-03386.2002"},{"key":"R13","unstructured":"Exner R, Wessner B, Manhart N, Roth E.Therapeutic potential of glutathione.Wien Klin Wochenschr112: 610\u2013616, 2000."},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118351"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2008.04.005"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.11.130"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6878"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00044.x"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.661"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-1815fje"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-200101000-00002"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1161\/hy02t2.102992"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.61.02.0010"},{"key":"R24","unstructured":"Lowicka E, Beltowski J.Hydrogen sulfide (H2S)\u2014the third gas of interest for pharmacologists.Pharmacol Rep59: 4\u201324, 2007."},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.79.6.1180"},{"key":"R26","unstructured":"McCully KS.Chemical pathology of homocysteine. 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