{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:59:27Z","timestamp":1780538367800,"version":"3.54.1"},"reference-count":50,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"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":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>Hepatic ischemia\/reperfusion (I\/R) injury is a syndrome involved in allograft dysfunction. This work aimed to elucidate carvedilol (CAR) role in hepatic I\/R injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Male rats were allocated to Sham group, CAR group, I\/R group and CAR plus I\/R group. Rats subjected to hepatic ischemia for 30 minutes then reperfused for 60 minutes. Oxidative stress markers, inflammatory cytokines and nitric oxide synthases were measured in hepatic tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Hepatocyte injury following I\/R was confirmed by a marked increase in liver enzymes. Also, hepatic I\/R increased the contents of malondialdehyde however decreased glutathione contents and activities of antioxidant enzymes. Furthermore, hepatic I\/R caused elevation of toll-like receptor-4 (TLR-4) expression and inflammatory mediators levels such as tumor necrosis factor-\u03b1, interleukin-6 and cyclooxygenase-II. Hepatic I\/R caused down-regulation of endothelial nitric oxide synthase and upregulation of inducible nitric oxide synthase expressions. CAR treatment before hepatic I\/R resulted in the restoration of liver enzymes. Administration of CAR caused a significant correction of oxidative stress and inflammation markers as well as modulates the expression of endothelial and inducible nitric oxide synthase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>CAR protects liver from I\/R injury through reduction of the oxidative stress and inflammation, and modulates endothelial and inducible nitric oxide synthase expressions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0960327121999442","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T05:47:37Z","timestamp":1614750457000},"page":"1362-1373","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Role of TLR-4\/IL-6\/TNF-\u03b1, COX-II and eNOS\/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury"],"prefix":"10.1177","volume":"40","author":[{"given":"Mohamed IA","family":"Hassan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fares EM","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2568-4133","authenticated-orcid":false,"given":"Abdel-Gawad S","family":"Shalkami","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, 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