{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:47:38Z","timestamp":1788580058153,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatocellular carcinoma (HCC) continues to be the most prevalent type of liver cancer worldwide. Diethylnitrosamine (DEN)\u2010induced HCC is an extensively used hepatic cancer model in experimental animals. Acetazolamide (AZA) is a carbonic anhydrase enzyme inhibitor. This study aimed to assess the therapeutic mechanism of AZA against DEN\u2010induced HCC. Thirty male <jats:italic>Wistar<\/jats:italic> albino rats were divided equally into three groups. Group I (C): control group, Group II (HCC): DEN\u2010induced HCC, and Group III (HCC\/AZA): AZA\u2010treated HCC. Verification of the HCC induced by DEN was confirmed by elevated liver enzymes' activities, and increased \u03b1\u2010fetoprotein (AFP) levels, as well as distinct liver architecture changes. On the other hand, the AZA\u2010treated HCC group experienced decreases in the activities of serum liver enzymes and AFP levels, as well as, regulated liver architecture. Additionally, it downregulated p\u2010p38 MAPK\/p\u2010JNK1\/JNK2\/p\u2010C\u2010Jun\/p\u2010NF\u2010\u03baB p65 protein expressions. Moreover, it ameliorated autophagy by controlling the expression of the p\u2010AMPK\/p\u2010mTOR1\/LC3 I\/II proteins. Furthermore, it downregulated the relative gene expressions of carbonic anhydrase\u2010IX (CAIX) and hexokinase\u2010II (HKII). Histopathological examination of AZA\u2010treated HCC liver tissues supported these findings. Conclusion: AZA provides a new dimension in ameliorating experimentally induced HCC through regulation of hepatic biomarkers, antioxidant status, inflammatory markers, and autophagy, mediated by amelioration of CAIX and HKII gene expressions.<\/jats:p>","DOI":"10.1111\/fcp.13032","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T01:56:15Z","timestamp":1724291775000},"page":"1045-1058","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Acetazolamide suppresses the progression of hepatocellular carcinoma induced by diethylnitrosamine in <i>Wistar<\/i> albino rats"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2446-7986","authenticated-orcid":false,"given":"Yomna M.","family":"Tamim","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed L.","family":"Soliman","sequence":"additional","affiliation":[{"name":"Internal Medicine Department Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8572-3341","authenticated-orcid":false,"given":"Moataz M.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Internal Medicine Department Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad S.","family":"Abdul\u2010Rasheed","sequence":"additional","affiliation":[{"name":"Hepatologist and gastroenterologist at Cairo Fatemic Hospital  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Nagy","sequence":"additional","affiliation":[{"name":"Clinical Oncology and Nuclear Medicine Department Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Abdellah","sequence":"additional","affiliation":[{"name":"Pathophysiology Department Grand Canyon University  Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.","family":"Osman","sequence":"additional","affiliation":[{"name":"Pathology Department Faculty of Veterinary Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3446-2372","authenticated-orcid":false,"given":"Amel F. M.","family":"Ismail","sequence":"additional","affiliation":[{"name":"Drug Radiation Research Department Biotechnology Division National Center for Radiation Research and Technology (NCRRT) Egyptian Atomic Energy Authority  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2023.109701"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010020\u201000240\u20103"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111868"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12990"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgh3.12753"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.34869"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32779"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22937"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13153651"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111636"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp170279"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2016.12.003"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2021.128249"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21145001"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.11.023"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136753"},{"key":"e_1_2_11_18_1","volume-title":"Potential anti\u2010carcinogenic effect of acetazolamide, a carbonic anhydrase enzyme inhibitor, in Diethylnitrosamine \u2013 induced Hepatocarcinogenesis in rats","author":"Abdul\u2010Rasheed MS","year":"2020"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcab100.141"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27551"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.167270"},{"issue":"1","key":"e_1_2_11_22_1","first-page":"89","article-title":"The suitability of Propofol compared with urethane for anesthesia during urodynamic studies in rats","volume":"55","author":"Moheban AA","year":"2016","journal-title":"J am Assoc Lab Anim Sci"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u20107020\u20106864\u20105.00010\u20104"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009\u20108981(78)90081\u20105"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/an9618600036"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20109861(59)90090\u20106"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006\u2010291x(72)80218\u20103"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010091302\u20102.50032\u20103"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.179.4073.588"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(19)52451\u20106"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512224"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110786"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amsu.2021.102458"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/c7ra12775h"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2016.07.004"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2012.736979"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.2004592"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.03.068"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2467"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710790979999"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/13645706.2022.2040535"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(19)68900\u20103"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.28.16918"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10863\u2010019\u201009788\u20106"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.225177"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.11.020"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.08.054"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11081053"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.08.021"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2009.02.004"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100038\u20101676806"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01421"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/6050123"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp\u20102018\u20100334"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658\u2010016\u20100031\u2010z"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.04.006"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.2147\/HMER.S63700"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.161"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168085"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom9100530"},{"issue":"1","key":"e_1_2_11_62_1","first-page":"1","article-title":"Expression of autophagy related genes mTOR, Becline\u20101, LC3 and p62 in the peripheral blood mononuclear cells of systemic lupus erythematosus","volume":"6","author":"Wu ZZ","year":"2017","journal-title":"Am J Clin Exp Immunol"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2016211"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9647"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.10197"}],"container-title":["Fundamental &amp; Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.13032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T03:40:39Z","timestamp":1731555639000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/fcp.13032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,20]]},"references-count":64,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/fcp.13032"],"URL":"https:\/\/doi.org\/10.1111\/fcp.13032","archive":["Portico"],"relation":{},"ISSN":["0767-3981","1472-8206"],"issn-type":[{"value":"0767-3981","type":"print"},{"value":"1472-8206","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,20]]},"assertion":[{"value":"2024-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}