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This study aims to identify differentially expressed proteins (DEPs) associated with the protective effects of hydrogen-rich saline (HRS) against N-methyl-N-nitrosourea (MNU)-induced cataracts, utilizing the antioxidant properties of hydrogen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sprague\u2013Dawley rats were assigned to control, MNU-only, MNU\u2009+\u2009normal saline (NS), MNU\u2009+\u2009pirenoxine(PRX), and MNU\u2009+\u2009HRS groups. Cataracts were induced with MNU (postnatal day 15), and treatments (postnatal days 8\u201321) included intraperitoneal injections and eye drops. Cataract severity was assessed using slit-lamp examinations, Pentacam analysis, and spectrophotometry. Proteomic analysis of lens tissues from the MNU\u2009+\u2009HRS and MNU\u2009+\u2009NS groups employed tandem mass tag (TMT) labeling and mass spectrometry. DEPs were identified, grouped based on fold changes, and analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG),, and domain enrichment. Parallel reaction monitoring (PRM) validated selected DEPs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HRS reduced MNU-induced cataract incidence to 50% versus 100% in MNU-only and NS groups and preserved lens clarity comparable to normal controls. Proteomic analysis identified 90 upregulated and 303 downregulated proteins in the HRS-treated group versus the NS-treated group. DEPs were enriched in GO terms related to ion transport, homeostasis, and ATP hydrolysis, as well as KEGG pathways like oxidative phosphorylation and arginine biosynthesis. Domain enrichment showed links to ATPase activity and energy metabolism. DEPs were grouped into Q1\u2013Q4, with Q1 showing enrichment in oxidative phosphorylation and metabolic pathways. PRM confirmed the downregulation of 14 stress-response and metabolic proteins in the HRS-treated group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HRS mitigates MNU-induced cataracts possibly by reducing oxidative stress and downregulating stress-response and metabolic proteins.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10792-025-03915-6","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T06:51:24Z","timestamp":1768891884000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydrogen-rich saline treatment modulates proteomic profiles to mitigate cataract development in a N-methyl-N-nitrosourea-induced rat model"],"prefix":"10.1007","volume":"46","author":[{"given":"Yingxin","family":"Qu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runpu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"3915_CR1","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/S0140-6736(22)01839-6","volume":"401","author":"MV Cicinelli","year":"2023","unstructured":"Cicinelli MV, Buchan JC, Nicholson M, Varadaraj V, Khanna RC (2023) Cataracts. 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