{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:31:33Z","timestamp":1784287893109,"version":"3.55.0"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The present research focused on estimating, for the first time, the potential protective effects of bromelain against D-galactosamine-induced acute liver injury in rats as well as identifying the possible underlying mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Silymarin (100 mg\/kg\/day, p.o.) as a reference drug or bromelain (20 and 40 mg\/kg\/day, p.o.) were administered for 10 days, and on the 8th day of the experiment, a single dose of galactosamine (400 mg\/kg\/i.p.) induced acute liver injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Pretreatment with bromelain improved liver functions and histopathological alterations induced by galactosamine. Bromelain ameliorated oxidative stress by inducing SIRT1 protein expression and increasing LKB1 content. This resulted in phosphorylating the AMPK\/GSK3\u03b2 axis, which stimulated Nrf2 activation in hepatic cells and thus increased the activity of its downstream antioxidant enzymes [HO-1 and NQO1]. Besides, bromelain exerted significant anti-apoptotic and anti-inflammatory effects by suppressing hepatic contents of TNF-\u03b1, NF-\u03baB p65, as well as caspase-8 and caspase-9. The protective effects of bromelain40 were proved to be better than silymarin and bromelain20 in most of the assessed parameters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results highlight the significant hepatoprotective effects of bromelain against acute liver injury through modulation of SIRT1\/LKB1\/AMPK, GSK3\u03b2\/Nrf2 signalling in addition to NF-\u03baB p65\/TNF-\u03b1\/ caspase-8 and -9 pathway.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgac071","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T15:48:26Z","timestamp":1665676106000},"page":"1765-1775","source":"Crossref","is-referenced-by-count":32,"title":["Bromelain ameliorates D-galactosamine-induced acute liver injury: role of SIRT1\/LKB1\/AMPK, GSK3\u03b2\/Nrf2 and NF-\u03baB p65\/TNF-\u03b1\/caspase-8, -9 signalling pathways"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6602-6815","authenticated-orcid":false,"given":"Manar A","family":"Didamoony","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, Egyptian Russian University ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M","family":"Atwa","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, Egyptian Russian University ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enas A","family":"Abd El-Haleim","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamiaa A","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, 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