{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:08:41Z","timestamp":1791544121578,"version":"4.3.4"},"reference-count":75,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":223,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>This study is aimed at evaluating the preventive effect and at suggesting the mode of actions of naringin and hesperidin and their combination in diclofenac\u2010induced hepatotoxicity. Male Wistar rats, intraperitoneally injected with diclofenac sodium (3\u2009mg\/kg b.wt\/day), were orally treated with naringin (20\u2009mg\/kg b.wt\/day) and hesperidin (20\u2009mg\/kg b.wt\/day) and their combination for 4 weeks. The administrations of naringin and hesperidin to diclofenac\u2010injected rats led to a significant decrease in the elevated serum ALT, AST, LDH, ALP, GGT, total bilirubin, TNF\u2010<jats:italic>\u03b1<\/jats:italic>, and IL\u201017 levels as well as liver lipid peroxidation and liver p53 and caspase\u20103 mRNA expressions. In contrast, serum IL\u20104 level, liver GSH content, and liver GPx and SOD activities increased. In association, diclofenac\u2010induced deleterious histological alterations including hydropic degeneration, cytoplasmic vacuolization, apoptosis, and focal hepatic necrosis of hepatocytes associated with inflammatory cells\u2019 infiltration were remarkably improved by treatments with naringin and hesperidin. In conclusion, naringin, hesperidin, and their combination, which was the most potent, counteract diclofenac\u2010induced liver injury <jats:italic>via<\/jats:italic> antioxidant, anti\u2010inflammatory, and antiapoptotic actions. Thus, this study recommends the use of naringin and hesperidin or their combination to resolve the side effects of drugs like diclofenac on the liver.<\/jats:p>","DOI":"10.1155\/2021\/9990091","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:05:07Z","timestamp":1628813107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Naringin and Hesperidin Counteract Diclofenac\u2010Induced Hepatotoxicity in Male Wistar Rats <i>via<\/i> Their Antioxidant, Anti\u2010Inflammatory, and Antiapoptotic Activities"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-897X","authenticated-orcid":false,"given":"Rasha A.","family":"Hassan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1981-8382","authenticated-orcid":false,"given":"Walaa G.","family":"Hozayen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2013-1895","authenticated-orcid":false,"given":"Haidy T.","family":"Abo Sree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5054-4610","authenticated-orcid":false,"given":"Hessah M.","family":"Al-Muzafar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2487-8427","authenticated-orcid":false,"given":"Kamal A.","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3781-9709","authenticated-orcid":false,"given":"Osama M.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"e_1_2_9_1_2","article-title":"Review of non-steroidal anti-inflammatory drugs","volume":"10","author":"Suryavanshi H.","year":"2019","journal-title":"International Journal of Advanced Scientific Research and Management"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.12991\/marupj.323595"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0392-z"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/2397847319874359"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.15171\/jhp.2019.23"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1368351"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2013.11.003"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5256"},{"key":"e_1_2_9_9_2","first-page":"730","article-title":"Protective effect of hesperidin against cyclophosphamide hepatotoxicity in rats","volume":"8","author":"Fouad A. A.","year":"2014","journal-title":"International Journal of Biological, Biomolecular, Agricultural, Food and Biotechnological Engineering"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-018-5222-y"},{"key":"e_1_2_9_11_2","first-page":"671","article-title":"Amelioration of cardiotoxic impacts of diclofenac sodium by vitamin B complex","volume":"19","author":"Abdulmajeed N. A.","year":"2015","journal-title":"European Review for Medical Pharmacological Sciences"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.20203"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2014.11.003"},{"key":"e_1_2_9_14_2","volume-title":"Alanine aminotransferase","author":"Murray R.","year":"1984"},{"key":"e_1_2_9_15_2","volume-title":"Aspartate aminotransferase","author":"Murray R.","year":"1984"},{"key":"e_1_2_9_16_2","first-page":"639","article-title":"Approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part 8. IFCC method for LDH","volume":"32","author":"Bais R.","year":"1994","journal-title":"European Journal Clinical Chemistry and Clinical Biochemistry"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000459586"},{"key":"e_1_2_9_18_2","article-title":"Kinetic colorimetric method for determination of serum gamma glutamyltransferase","volume":"12","author":"Szasz G.","year":"1974","journal-title":"Clin. Chem. Clin. Biochem"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(71)90365-2"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)74392-5"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.1998.10718736"},{"key":"e_1_2_9_22_2","first-page":"882","article-title":"Improved method for the determination of blood glutathione","volume":"61","author":"Beutler E.","year":"1963","journal-title":"The Journal of Laboratory and Clinical Medicine"},{"key":"e_1_2_9_23_2","first-page":"29","article-title":"Oxidative stress in experimental diabetes induced by streptozotocin","volume":"85","author":"Matkovics B.","year":"1998","journal-title":"Acta Physiologica Hungarica"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1974.tb03714.x"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1987.9999"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.28.3.495-503.1990"},{"key":"e_1_2_9_27_2","volume-title":"Molecular Cloning Laboratory Manual","author":"Sambrook J.","year":"2008"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.4161\/oxim.3.5.13107"},{"key":"e_1_2_9_29_2","volume-title":"Theory and Practice of Histological Techniques","author":"Banchroft J. D.","year":"1996"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.4172\/2157-7099.s4-001"},{"key":"e_1_2_9_31_2","first-page":"823","article-title":"Thymoquinone and curcumin prevent gentamicin-induced liver injury by attenuating oxidative stress, inflammation and apoptosis","volume":"65","author":"Galaly S. R.","year":"2014","journal-title":"Journal of Physiology and Pharmacology"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.4172\/1948-5956.1000272"},{"key":"e_1_2_9_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096801"},{"key":"e_1_2_9_34_2","volume-title":"One Way Analysis of Variance","author":"Roa M.","year":"1985"},{"key":"e_1_2_9_35_2","first-page":"663","article-title":"Evaluation of analgesic activity of different brands of diclofenac sodium using trail flick method","volume":"5","author":"Chouhan A.","year":"2016","journal-title":"World Journal of Pharmacy and Pharmaceutical Sciences"},{"key":"e_1_2_9_36_2","first-page":"5021","article-title":"Examination of the pharmacodynamics and pharmacokinetics of a diclofenac poly (lactic-co-glycolic) acid nanoparticle formulation in the rat","volume":"20","author":"Harirforoosh S.","year":"2016","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/5253623"},{"key":"e_1_2_9_38_2","doi-asserted-by":"publisher","DOI":"10.1177\/2042098617690485"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11101-017-9497-1"},{"key":"e_1_2_9_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2016.04.115"},{"key":"e_1_2_9_41_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612826666201127122313"},{"key":"e_1_2_9_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2004.07.005"},{"key":"e_1_2_9_43_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2745352"},{"key":"e_1_2_9_44_2","first-page":"96","article-title":"The nephropreventive and antioxidant effects of navel orange peel hydroethanolic extract, naringin and naringenin in n-acetyl-p-aminophenol-administered Wistar rats","volume":"7","author":"Ahmed O. M.","year":"2019","journal-title":"Advances in Animal and Veterinary Sciences"},{"key":"e_1_2_9_45_2","doi-asserted-by":"publisher","DOI":"10.3844\/ajptsp.2007.80.88"},{"key":"e_1_2_9_46_2","first-page":"363","article-title":"Protective effect of L carnitine against diclofenac sodium toxicity in mice","volume":"159","author":"Yapar K.","year":"2008","journal-title":"Revista de Medicina Veterinaria"},{"key":"e_1_2_9_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1995-7645(11)60100-4"},{"key":"e_1_2_9_48_2","first-page":"185","article-title":"Hepatoprotective activity of Mikania Scandens (L.) Willd. against diclofenac sodium induced liver toxicity in rats","volume":"5","author":"Maity T.","year":"2012","journal-title":"Asian Journal of Pharmaceutical and Clinical Research"},{"key":"e_1_2_9_49_2","first-page":"1548","article-title":"Ameliorative effect of 10-gingerol on drug induced hepatotoxicity in albino rats","volume":"6","author":"Alqasoumi S. I.","year":"2012","journal-title":"J. Med. Plants Res"},{"key":"e_1_2_9_50_2","doi-asserted-by":"publisher","DOI":"10.21608\/bvmj.2016.31406"},{"key":"e_1_2_9_51_2","doi-asserted-by":"publisher","DOI":"10.5138\/09750185.2081"},{"key":"e_1_2_9_52_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom10091317"},{"key":"e_1_2_9_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.1.705"},{"key":"e_1_2_9_54_2","doi-asserted-by":"publisher","DOI":"10.1159\/000053951"},{"key":"e_1_2_9_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-013-0861-4"},{"key":"e_1_2_9_56_2","article-title":"Possible protective role of ginger extract on diclofenac induced hepatotoxicity in adult male albino rats (histological and ultrastructural studies)","volume":"11","author":"El-Kordy E. A.","year":"2014","journal-title":"Life Science Journal"},{"key":"e_1_2_9_57_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.142.2.198"},{"key":"e_1_2_9_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.06.039"},{"key":"e_1_2_9_59_2","doi-asserted-by":"publisher","DOI":"10.7324\/japs.2018.81010"},{"key":"e_1_2_9_60_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00494.2001"},{"key":"e_1_2_9_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.05.004"},{"key":"e_1_2_9_62_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425251003601979"},{"key":"e_1_2_9_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2015.09.007"},{"key":"e_1_2_9_64_2","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2015.49484"},{"key":"e_1_2_9_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-010-0295-0"},{"key":"e_1_2_9_66_2","first-page":"129","article-title":"Naringin inhibits tumor growth and reduces interleukin-6 and tumor necrosis factor \u03b1 levels in rats with Walker 256 carcinosarcoma","volume":"32","author":"Camargo C. A.","year":"2012","journal-title":"Anticancer Research"},{"key":"e_1_2_9_67_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2013.1403"},{"key":"e_1_2_9_68_2","doi-asserted-by":"publisher","DOI":"10.4172\/2469-9756.1000107"},{"key":"e_1_2_9_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2016.05.015"},{"key":"e_1_2_9_70_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-018-2242-5"},{"key":"e_1_2_9_71_2","first-page":"484","article-title":"Antitoxic effects of naringin: a flavonoid with diverse biological activities","volume":"7","author":"Singh Z.","year":"2018","journal-title":"World Journal of Pharmaceutical Research"},{"key":"e_1_2_9_72_2","first-page":"18","article-title":"Protective effect of hesperidin against methotrexate-induced nephrotoxicity in rats","volume":"16","author":"Aldossary S. A.","year":"2019","journal-title":"Life Science Journal"},{"key":"e_1_2_9_73_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-018-1443-6"},{"key":"e_1_2_9_74_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1730492"},{"key":"e_1_2_9_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.07.094"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/9990091.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/9990091.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2021\/9990091","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T18:55:44Z","timestamp":1723056944000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2021\/9990091"}},"subtitle":[],"editor":[{"given":"Anderson J.","family":"Teodoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":75,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1155\/2021\/9990091"],"URL":"https:\/\/doi.org\/10.1155\/2021\/9990091","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2021-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"9990091"}}