{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:15:20Z","timestamp":1789398920125,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research &amp; Innovation, Ministry of Education in Saudi Arabia","award":["IFP22UQU4340212DSR168"],"award-info":[{"award-number":["IFP22UQU4340212DSR168"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Paracetamol or acetaminophen (PAC) is a commonly used analgesic and antipyretic drug. It has been shown that overdoses beyond the therapeutic range can cause hepatotoxicity and acute liver injury. The most common cause of drug-induced liver injury (DILI) in Saudi Arabia and worldwide is paracetamol overdose. Fucoxanthin (FUC) is an allenic carotenoid that is found in edible brown seaweeds, and it has antioxidant and anti-inflammatory effects. Several studies have shown the potential therapeutic effects of FUC in diabetes, cancers, and inflammatory disorders. This study aims to investigate the protective effect of FUC against PAC-induced acute liver injury in rats. FUC was administered (100, 200, and 500 mg\/kg, p.o.) for 7 days, and then the liver injury was induced by the administration of PAC (2000 mg\/kg, oral). Blood and liver tissue samples were collected from PAC-positive untreated, treated, and negative control rats. Biochemical and inflammatory parameters in the blood were measured. In addition, RT-PCR, Western blotting, and immunohistochemistry were performed for liver tissue. The serum levels of liver biomarkers (ALT, AST, and ALP) increased after PAC-induced liver toxicity; FUC-treated rats showed lower levels compared to the positive control. There was an increase in the expression of TNF-\u03b1, IL-1, IL-6, NF-kB, INF-\u03b3, and iNOS and a decrease in IL-10, IL-22, and IL-10R expression after the FUC treatment of injured liver rats. For the hepatic inflammation and PAC-toxicity-induced oxidative stress genes and proteins, FUC-treated rats (100, 200, and 500 mg\/kg) showed a reduction in the expression of oxidative stress genes. These results showed that FUC protected the liver against PAC-induced injury through antioxidant and anti-inflammatory actions. However, further clinical studies are required to confirm the findings.<\/jats:p>","DOI":"10.3390\/md21110592","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T02:20:37Z","timestamp":1699928437000},"page":"592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Antioxidative and Anti-Inflammatory Protective Effects of Fucoxanthin against Paracetamol-Induced Hepatotoxicity in Rats"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0224-3122","authenticated-orcid":false,"given":"Maimonah Fuad","family":"Koshak","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah 24381, Saudi Arabia"},{"name":"Laboratory of Clinical Chemistry, King Salman Armed Forces Hospital, Tabuk 47512, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0252-2370","authenticated-orcid":false,"given":"Mahmoud Zaki","family":"El-Readi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah 24381, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6335-1778","authenticated-orcid":false,"given":"Mohamed Elzubier","family":"Elzubier","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah 24381, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4267-1016","authenticated-orcid":false,"given":"Bassem","family":"Refaat","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, P.O. Box 7607, Makkah 24381, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7944-2597","authenticated-orcid":false,"given":"Riyad Adnan","family":"Almaimani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah 24381, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakir","family":"Idris","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, P.O. Box 7607, Makkah 24381, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-3188","authenticated-orcid":false,"given":"Mohammad","family":"Althubiti","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah 24381, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba Saeed","family":"Al-Amodi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah 24381, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safaa Yehia","family":"Eid","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah 24381, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ji, M., Deng, Z., Rong, X., Li, R., You, Z., Guo, X., Cai, C., Zhao, Y., Gao, P., and Cao, G. (2022). Naringenin Prevents Oxidative Stress and Inflammation in LPS-Induced Liver Injury through the Regulation of LncRNA-mRNA in Male Mice. Molecules, 28.","DOI":"10.3390\/molecules28010198"},{"key":"ref_2","first-page":"2525","article-title":"Acute liver failure","volume":"369","author":"Bernal","year":"2013","journal-title":"Lancet"},{"key":"ref_3","first-page":"147","article-title":"Alcoholic Liver Disease: Pathogenesis and Current Management","volume":"38","author":"Osna","year":"2017","journal-title":"Alcohol Res. Curr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1111\/j.1572-0241.2007.01388.x","article-title":"Population-based surveillance for acute liver failure","volume":"102","author":"Bower","year":"2007","journal-title":"Am. J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/hep.23937","article-title":"Drug induced acute liver failure: Results of a US multicenter, prospective study","volume":"52","author":"Reuben","year":"2010","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"491","DOI":"10.4254\/wjh.v9.i10.491","article-title":"Drug-induced liver injury: Do we know everything?","volume":"9","author":"Alempijevic","year":"2017","journal-title":"World J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1001\/jama.296.1.87","article-title":"Aminotransferase elevations in healthy adults receiving 4 g of acetaminophen daily: A randomized controlled trial","volume":"296","author":"Watkins","year":"2006","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3109\/15360288.2014.908993","article-title":"Patient perception and knowledge of acetaminophen in a large family medicine service","volume":"28","author":"Herndon","year":"2014","journal-title":"J. Pain Palliat. Care Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.cld.2013.07.005","article-title":"Acetaminophen-related hepatotoxicity","volume":"17","author":"Bunchorntavakul","year":"2013","journal-title":"Clin. Liver Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Agrawal, S., and Khazaeni, B. (2022). Acetaminophen Toxicity, StatPearls Publishing.","DOI":"10.1287\/fa7d97f0-ba96-4959-a51b-cf12b34c6d20"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"947","DOI":"10.7326\/0003-4819-137-12-200212170-00007","article-title":"Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States","volume":"137","author":"Ostapowicz","year":"2002","journal-title":"Ann. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1016\/0006-2952(81)90576-1","article-title":"Drug-induced lipid peroxidation in mice\u2014I Modulation by monooxegenase activity, glutathione and selenium status","volume":"30","author":"Wendel","year":"1981","journal-title":"Biochem. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3109\/03602532.2011.602688","article-title":"Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity","volume":"44","author":"Jaeschke","year":"2012","journal-title":"Drug Metab. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/toxsci\/kfw158","article-title":"Editor\u2019s highlight: Metformin protects against acetaminophen hepatotoxicity by attenuation of mitochondrial oxidant stress and dysfunction","volume":"154","author":"Du","year":"2016","journal-title":"Toxicol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.30699\/jambs.31.145.170","article-title":"Hepatoprotective properties of Cuminum cyminum seeds powder as post-treatment for acetaminophen-induced acute hepatic injury","volume":"31","author":"Mozaffarinia","year":"2023","journal-title":"J. Adv. Med. Biomed. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1074\/mcp.RA118.000875","article-title":"Reactive Metabolite-induced Protein Glutathionylation: A Potentially Novel Mechanism Underlying Acetaminophen Hepatotoxicity","volume":"17","author":"Chan","year":"2018","journal-title":"Mol. Cell. Proteom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.redox.2016.10.001","article-title":"Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential","volume":"10","author":"Du","year":"2016","journal-title":"Redox Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, F.C., Lee, H.C., Liao, C.C., Chou, A.H., and Yu, H.P. (2023). Role of NADPH Oxidase-Derived ROS-Mediated IL-6\/STAT3 and MAPK\/NF-kappaB Signaling Pathways in Protective Effect of Corilagin against Acetaminophen-Induced Liver Injury in Mice. Biology, 12.","DOI":"10.3390\/biology12020334"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2147\/IMCRJ.S74563","article-title":"N-acetylcysteine overdose after acetaminophen poisoning","volume":"8","author":"Astaraki","year":"2015","journal-title":"Int. Med Case Rep. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nishino, A., Maoka, T., and Yasui, H.J.A. (2022). Preventive effects of \u03b2-cryptoxanthin, a potent antioxidant and provitamin A carotenoid, on lifestyle-related diseases\u2014A central focus on its effects on non-alcoholic fatty liver disease (NAFLD). Antioxidants, 11.","DOI":"10.3390\/antiox11010043"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Abenavoli, L., Procopio, A.C., Paravati, M.R., Costa, G., Mili\u0107, N., Alcaro, S., and Luzza, F. (2022). Mediterranean diet: The beneficial effects of lycopene in non-alcoholic fatty liver disease. J. Clin. Med., 11.","DOI":"10.3390\/jcm11123477"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"153280","DOI":"10.1016\/j.phymed.2020.153280","article-title":"The carotenoid fucoxanthin can sensitize multidrug resistant cancer cells to doxorubicin via induction of apoptosis, inhibition of multidrug resistance proteins and metabolic enzymes","volume":"77","author":"Eid","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1021\/jf405032f","article-title":"Purple sweet potato (Ipomoea batatas L.) anthocyanins: Preventive effect on acute and subacute alcoholic liver damage and dealcoholic effect","volume":"62","author":"Sun","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13183","DOI":"10.1021\/acs.jafc.8b05756","article-title":"Inhibition of P2X7R\u2013NLRP3 Inflammasome Activation by Pleurotus citrinopileatus: A Possible Protective Role in Alcoholic Hepatosteatosis","volume":"66","author":"Li","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14090","DOI":"10.1038\/s41598-018-32497-w","article-title":"Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity","volume":"8","author":"Han","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zheng, J., Tian, X., Zhang, W., Zheng, P., Huang, F., Ding, G., and Yang, Z. (2019). Protective effects of fucoxanthin against alcoholic liver injury by activation of Nrf2-mediated antioxidant defense and inhibition of TLR4-mediated inflammation. Mar. Drugs, 17.","DOI":"10.3390\/md17100552"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Shih, P.-H., Shiue, S.-J., Chen, C.-N., Cheng, S.-W., Lin, H.-Y., Wu, L.-W., and Wu, M.-S. (2021). Fucoidan and fucoxanthin attenuate hepatic steatosis and inflammation of NAFLD through modulation of leptin\/adiponectin axis. Mar. Drugs, 19.","DOI":"10.3390\/md19030148"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/aid2.13125","article-title":"Low-molecular-weight fucoidan and high-stability fucoxanthin decrease serum alanine transaminase in patients with nonalcoholic fatty liver disease\u2014A double-blind, randomized controlled trial","volume":"6","author":"Cheng","year":"2019","journal-title":"Adv. Dig. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1463-1326.2009.01132.x","article-title":"The effects of Xanthigen\u2122 in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat","volume":"12","author":"Abidov","year":"2010","journal-title":"Diabetes Obes. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12944-020-01419-z","article-title":"Association between the alanine aminotransferase\/aspartate aminotransferase ratio and new-onset non-alcoholic fatty liver disease in a nonobese Chinese population: A population-based longitudinal study","volume":"19","author":"Zou","year":"2020","journal-title":"Lipids Heal. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"26087","DOI":"10.3390\/ijms161125942","article-title":"The Role of Oxidative Stress and Antioxidants in Liver Diseases","volume":"16","author":"Li","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_32","first-page":"163","article-title":"STAT3, a key parameter of cytokine-driven tissue protection during sterile inflammation\u2013the case of experimental acetaminophen (paracetamol)-induced liver damage","volume":"7","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1021\/jf502990n","article-title":"Protective effect of panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress","volume":"63","author":"Ding","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"321S","DOI":"10.1378\/chest.112.6_Supplement.321S","article-title":"Proinflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock","volume":"112","author":"Dinarello","year":"1997","journal-title":"Chest"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.fct.2013.10.011","article-title":"Hepatoprotective effect of mulberry water extracts on ethanol-induced liver injury via anti-inflammation and inhibition of lipogenesis in C57BL\/6J mice","volume":"62","author":"Tang","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1039\/C8FO00650D","article-title":"Function, Targeting heme oxygenase-1 by quercetin ameliorates alcohol-induced acute liver injury via inhibiting NLRP3 inflammasome activation","volume":"9","author":"Liu","year":"2018","journal-title":"Food Funct."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jhep.2017.08.023","article-title":"IL-1 receptor like 1 protects against alcoholic liver injury by limiting NF-\u03baB activation in hepatic macrophages","volume":"68","author":"Wang","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1500899","DOI":"10.1002\/mnfr.201500899","article-title":"Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake, an effect related to the modulation of the gut microbiota","volume":"61","author":"Neyrinck","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mohammed, H.A., Eldeeb, H.M., Khan, R.A., Al-Omar, M.S., Mohammed, S.A.A., Sajid, M.S.M., Aly, M.S.A., Ahmad, A.M., Abdellatif, A.A.H., and Eid, S.Y. (2021). Sage, Salvia officinalis L. Constituents, Hepatoprotective Activity, and Cytotoxicity Evaluations of the Essential Oils Obtained from Fresh and Differently Timed Dried Herbs: A Comparative Analysis. Molecules, 26.","DOI":"10.3390\/molecules26195757"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/21\/11\/592\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:22:35Z","timestamp":1760131355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/21\/11\/592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,14]]},"references-count":39,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["md21110592"],"URL":"https:\/\/doi.org\/10.3390\/md21110592","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,14]]}}}