{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:03:48Z","timestamp":1780081428951,"version":"3.54.0"},"reference-count":57,"publisher":"Canadian Science Publishing","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p> Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin\u2013angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl<jats:sub>4<\/jats:sub>-induced liver fibrosis. Mice were treated with silymarin (30 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>), perindopril (1 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>), fosinopril (2 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>), or losartan (10 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>). The administration of RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (\u03b1-SMA) and hepatic content of hydroxyproline. These effects found to be mediated via inactivation of nuclear transcription factor kappa B (NF\u03baB) pathway by the inhibition of NF\u03baB p65 phosphorylation at the Ser536 residue and phosphorylation-induced degradation of nuclear factor kappa-B inhibitor alpha (NF\u03baBia) subsequently inhibited NF\u03baB-induced TNF-\u03b1 and TGF-\u03b21, leading to lower levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). We concluded that the tissue affinity of the angiotensin converting enzyme inhibitors (ACEIs) has no impact on its antifibrotic activity and that interfering the RAS either through the inhibition of ACE or the blockade of AT1R has the same therapeutic benefit. These results suggest RAS inhibitors as promising candidates for further clinical trials in the management of hepatic fibrosis. <\/jats:p>","DOI":"10.1139\/cjpp-2017-0728","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T22:34:33Z","timestamp":1518215673000},"page":"569-576","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Renin\u2013angiotensin system inhibition ameliorates CCl<sub>4<\/sub>-induced liver fibrosis in mice through the inactivation of nuclear transcription factor kappa B"],"prefix":"10.1139","volume":"96","author":[{"given":"Sameh","family":"Saber","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr A.A.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt."},{"name":"Department of Pharmacology, Oman Pharmacy Institute, Ministry of Health, Muscat, Sultanate of Oman."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha S.","family":"Helal","sequence":"additional","affiliation":[{"name":"Department of Pathology, Theodor Bilharz Research Institute, Giza, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"El-Ahwany","sequence":"additional","affiliation":[{"name":"Department of Immunology, Theodor Bilharz Research Institute, Giza, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha H.","family":"Abdelghany","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144509"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70368-4"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00037.2003"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00695-4"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840200104"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0754-5"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313509200"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00447.2006"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.1038\/srep21592"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-940-0:237"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.02.007"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512815200"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.1016\/0531-5565(95)02010-1"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.4236\/snl.2015.52005"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082190"},{"issue":"4","key":"refg18\/ref18","first-page":"219","volume":"50","author":"Freireich E.J.","year":"1966","journal-title":"Cancer Chemother. 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