{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:46:52Z","timestamp":1789958812277,"version":"4.0.1"},"reference-count":68,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T00:00:00Z","timestamp":1572912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at King Saud University","award":["RG-1440-018"],"award-info":[{"award-number":["RG-1440-018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Lead (Pb) is a toxic heavy metal pollutant with adverse effects on the liver and other body organs. Curcumin (CUR) is the principal curcuminoid of turmeric and possesses strong antioxidant and anti-inflammatory activities. This study explored the protective effect of CUR on Pb hepatotoxicity with an emphasis on oxidative stress, inflammation and Akt\/GSK-3\u03b2 signaling. Rats received lead acetate and CUR and\/or ascorbic acid (AA) for seven days and samples were collected for analyses. Pb(II) induced liver injury manifested by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as histopathological alterations, including massive hepatocyte degeneration and increased collagen deposition. Lipid peroxidation, nitric oxide, TNF-\u03b1 and DNA fragmentation were increased, whereas antioxidant defenses were diminished in the liver of Pb(II)-intoxicated rats. Pb(II) increased hepatic NF-\u03baB and JNK phosphorylation and caspase-3 cleavage, whereas Akt and GSK-3\u03b2 phosphorylation was decreased. CUR and\/or AA ameliorated liver function, prevented tissue injury, and suppressed oxidative stress, DNA damage, NF-\u03baB, JNK and caspase-3. In addition, CUR and\/or AA activated Akt and inhibited GSK-3\u03b2 in Pb(II)-induced rats. In conclusion, CUR prevents Pb(II) hepatotoxicity via attenuation of oxidative injury and inflammation, activation of Akt and inhibition of GSK-3\u03b2. However, further studies scrutinizing the exact role of Akt\/GSK-3\u03b2 signaling are recommended.<\/jats:p>","DOI":"10.3390\/biom9110703","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T02:48:31Z","timestamp":1573094911000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Curcumin Ameliorates Lead-Induced Hepatotoxicity by Suppressing Oxidative Stress and Inflammation, and Modulating Akt\/GSK-3\u03b2 Signaling Pathway"],"prefix":"10.3390","volume":"9","author":[{"given":"Ahlam","family":"Alhusaini","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Fadda","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman H.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enas","family":"Zakaria","sequence":"additional","affiliation":[{"name":"Pharmaceutics Department, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer M.","family":"Alenazi","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-6500","authenticated-orcid":false,"given":"Ayman M.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/bmb\/ldg032","article-title":"Hazards of heavy metal contamination","volume":"68","author":"Jarup","year":"2003","journal-title":"Br. 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