{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:51:47Z","timestamp":1790265107158,"version":"4.1.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2019,9,22]],"date-time":"2019-09-22T00:00:00Z","timestamp":1569110400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                    Methotrexate (MTX) is a commonly used anticancer and immunosuppressive agent. However, MTX can induce hepatotoxicity due to oxidative stress, inflammation, and apoptosis. Hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S), the endogenous gaseous molecule, has antioxidant, anti-inflammatory, and anti-apoptotic effects. The present work explored the probable protective effect of H\n                    <jats:sub>2<\/jats:sub>\n                    S against MTX hepatotoxicity in rats and also the possible mechanisms underlying this effect. MTX was given at a single intraperitoneal (i.p.) dose of 20 mg\/kg. Sodium H\n                    <jats:sub>2<\/jats:sub>\n                    S (56 \u00b5mol \/kg\/day, i.p.), as H\n                    <jats:sub>2<\/jats:sub>\n                    S donor, was given for 10 days, starting 6 days before MTX administration. H\n                    <jats:sub>2<\/jats:sub>\n                    S significantly reduced serum alanine aminotransferase, hepatic malondialdehyde, interleukin 6, nuclear factor \u03baB p65, cytosolic cytochrome c, phosphorylated signal transducer and activator of transcription 3, and Bax\/Bcl-2 ratio and significantly increased hepatic total antioxidant capacity and endothelial nitric oxide synthase (eNOS) in rats received MTX. In addition, H\n                    <jats:sub>2<\/jats:sub>\n                    S minimized the histopathological injury and significantly decreased the expression of STAT3 in liver tissue of MTX-challenged rats. The effects of H\n                    <jats:sub>2<\/jats:sub>\n                    S were significantly antagonized by administration of glibenclamide as K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel blocker, N\u03c9-nitro-l-arginine, as eNOS inhibitor, or ruthenium red, as transient receptor potential vanilloid 1 (TRPV1) antagonist. It was concluded that H\n                    <jats:sub>2<\/jats:sub>\n                    S provided significant hepatoprotection in MTX-challenged rats through its antioxidant, anti-inflammatory, anti-apoptotic effects. These effects are most probably mediated by the ability of H\n                    <jats:sub>2<\/jats:sub>\n                    S to act as IL-6\/STAT3 pathway modulator, K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel opener, eNOS activator, and TRPV1 agonist.\n                  <\/jats:p>","DOI":"10.1177\/0960327119877437","type":"journal-article","created":{"date-parts":[[2019,9,22]],"date-time":"2019-09-22T23:06:22Z","timestamp":1569193582000},"page":"77-85","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":44,"title":["Hydrogen sulfide modulates IL-6\/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2079-2781","authenticated-orcid":false,"given":"AA","family":"Fouad","sequence":"first","affiliation":[{"name":"Department of 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