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Ischaemia\u2010reoxygenation (IR) injury causes several deleterious effects. We evaluated the protective effects of a selective inhibitor of \u03b3\u2010GT in experimentally induced IR injury in rats with obesity and steatosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Otsuka Long\u2010Evans Tokushima Fatty (OLETF) rats with hepatic steatosis were used in the current study. The portal vein and hepatic artery of left lateral and median lobes were clamped to induce ischaemia. Before clamping, 1 ml of saline (IR group) or 1\u2010ml saline containing 1 mg\u00b7kg<jats:sup>\u22121<\/jats:sup> body weight of GGsTop (\u03b3\u2010GT inhibitor; IR\u2010GGsTop group) was injected into the liver via the inferior vena cava. Blood flow was restored after at 30 min of the start of ischaemia. Blood was collected before, at 30 min after ischaemia and at 2 h and 6 h after reoxygenation. All the animals were killed at 6 h and the livers were collected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Treatment with GGsTop resulted in significant reduction of serum ALT, AST and \u03b3\u2010GT levels and hepatic \u03b3\u2010GT, malondialdehyde, 4\u2010hydroxy\u20102\u2010nonenal and HMGB1 at 6 h after reoxygenation. Inhibition of \u03b3\u2010GT retained normal hepatic glutathione levels. There was prominent hepatic necrosis in IR group, which is significantly reduced in IR\u2010GGsTop group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Treatment with GGsTop significantly increased hepatic glutathione content, reduced hepatic MDA, 4\u2010HNE and HMGB1 levels and, remarkably, ameliorated hepatic necrosis after ischaemia\u2010reoxygenation. The results indicated that GGsTop could be an appropriate therapeutic agent to reduce IR\u2010induced liver injury in obesity and steatosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15258","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T06:46:13Z","timestamp":1601189173000},"page":"5195-5207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of \u03b3\u2010glutamyltransferase ameliorates ischaemia\u2010reoxygenation tissue damage in rats with hepatic steatosis"],"prefix":"10.1111","volume":"177","author":[{"given":"Ryuichi","family":"Kubota","sequence":"first","affiliation":[{"name":"Department of Hepatology Kanazawa Medical University  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuhiko","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Hepatology Kanazawa Medical University  Uchinada Japan"},{"name":"Center for Regenerative Medicine Kanazawa Medical University Hospital  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Hepatology Kanazawa Medical University  Uchinada Japan"},{"name":"Center for Regenerative Medicine Kanazawa Medical University Hospital  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Hepatology Kanazawa Medical University  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuaki","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Hepatology Kanazawa Medical University  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshimichi","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Pathology II Kanazawa Medical University  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutsumi","family":"Tsuchishima","sequence":"additional","affiliation":[{"name":"Department of Hepatology Kanazawa Medical University  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikihiro","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Department of Hepatology Kanazawa Medical University  Uchinada Japan"},{"name":"Center for Regenerative Medicine Kanazawa Medical University Hospital  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5354-7884","authenticated-orcid":false,"given":"Joseph","family":"George","sequence":"additional","affiliation":[{"name":"Department of Hepatology Kanazawa Medical University  Uchinada Japan"},{"name":"Center for Regenerative Medicine Kanazawa Medical University Hospital  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.15171\/jrip.2019.18"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"issue":"1","key":"e_1_2_11_4_1","first-page":"S297","article-title":"The Concise Guide to PHARMACOLOGY 2019\/20: Enzymes","volume":"176","author":"Alexander S. 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