{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T02:17:35Z","timestamp":1781144255732,"version":"3.54.1"},"reference-count":62,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T00:00:00Z","timestamp":1518566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>Paracetamol (P), one of the most popular and commonly used analgesic and antipyretic agents, causes hepatotoxicity in overdoses. Amlodipine (AML), an L-type calcium channel blocker, has been shown to have anti-inflammatory activity by reversing the effect of calcium in the inflammation pathogenesis. In this study, the hepatoprotective activity of AML on P-induced hepatotoxicity was evaluated. Thirty male albino Wistar rats were divided into five groups: (1) control, (2) 2 g\/kg of P, (3) 2 g\/kg of P + 5 mg\/kg of AML, (4) 2 g\/kg of P + 10 mg\/kg of AML, and (5) 10 mg\/kg of AML. Some liver enzymes, oxidative parameters, cytokine mRNA expressions, histopathology, and immunohistochemical studies were performed in liver and blood samples. The serum levels of alanine aminotransferase and aspartate aminotransferase and the mRNA expression of tumor necrosis factor-alpha (TNF-\u03b1) and transforming growth factor-beta in the liver tissues were significantly increased in the group treated with P. The superoxide dismutase and glutathione parameters decreased and malondialdehyde levels increased in the livers of the rats treated with P. All these parameters were increased with both doses of the AML similar to the control group. A histopathological examination of the liver showed that AML administration ameliorated the P-induced inflammatory liver damage. In immunohistochemical staining, the expression of TNF-\u03b1 in the cytoplasm of the hepatocytes was increased in the P group but not in other treatment groups when compared to the control. In conclusion, AML treatment showed significant protective effects against P-induced hepatotoxicity by increasing the activity of antioxidants and reducing inflammatory cytokines.<\/jats:p>","DOI":"10.1177\/0960327118758382","type":"journal-article","created":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T06:40:02Z","timestamp":1518590402000},"page":"1169-1179","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Protective effect of an L-type calcium channel blocker, amlodipine, on paracetamol-induced hepatotoxicity in rats"],"prefix":"10.1177","volume":"37","author":[{"given":"H","family":"Kaya","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Department of Pharmacology, Ataturk University, Erzurum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Polat","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ataturk University, Erzurum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Albayrak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pharmacology, Ataturk University, Erzurum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Mercantepe","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Histology and Embryology, Recep Tayyip Erdogan University, Rize, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Buyuk","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Histology and Embryology, Canakkale Onsekiz Mart University, Canakkale, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,2,14]]},"reference":[{"key":"bibr1-0960327118758382","unstructured":"Sherlock S, Dooley J. Disease of the liver and miliary system, 10th ed. Oxford: Balckwell Scientific Publications, 1997, pp. 103\u2013117."},{"key":"bibr2-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1136\/gut.35.6.809"},{"key":"bibr3-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1002\/lt.500050102"},{"key":"bibr4-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1186\/cc1475"},{"key":"bibr5-0960327118758382","first-page":"765","volume":"10","author":"Lewis RK","year":"1991","journal-title":"Clin Pharm"},{"key":"bibr6-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90758-0"},{"key":"bibr7-0960327118758382","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198325030-00002"},{"key":"bibr8-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1080\/20014091111677"},{"key":"bibr9-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.06.030"},{"key":"bibr10-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2003.00050.x"},{"key":"bibr11-0960327118758382","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.6.3414"},{"key":"bibr12-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(01)00729-8"},{"key":"bibr13-0960327118758382","first-page":"5","volume":"9","author":"Trocha M","year":"2004","journal-title":"Ann Transplant"},{"key":"bibr14-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.27.877"},{"key":"bibr15-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfi336"},{"key":"bibr16-0960327118758382","first-page":"692","volume":"58","author":"Suleyman H","year":"2006","journal-title":"Pharmacol Rep"},{"key":"bibr17-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1191\/096032701667736070"},{"key":"bibr18-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1159\/000138932"},{"key":"bibr19-0960327118758382","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0022-3565(25)31909-9","volume":"212","author":"Schmidt WK","year":"1980","journal-title":"J Pharmacol Exp Ther"},{"key":"bibr20-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-09-0467"},{"key":"bibr21-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07529.x"},{"key":"bibr22-0960327118758382","doi-asserted-by":"publisher","DOI":"10.4318\/tjg.2010.0125"},{"key":"bibr23-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-001-1243-0"},{"key":"bibr24-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.01.022"},{"key":"bibr25-0960327118758382","doi-asserted-by":"publisher","DOI":"10.3109\/08923973.2013.775589"},{"key":"bibr26-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25313"},{"key":"bibr27-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/34.3.497"},{"key":"bibr28-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(68)90092-4"},{"key":"bibr29-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"bibr30-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-014-1014-0"},{"key":"bibr31-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"bibr32-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00005-9"},{"key":"bibr33-0960327118758382","doi-asserted-by":"publisher","DOI":"10.5897\/AJPP12.658"},{"key":"bibr34-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1177\/0960327112472994"},{"key":"bibr35-0960327118758382","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/S0026-895X(25)14551-3","volume":"18","author":"Corcoran GB","year":"1980","journal-title":"Mol Pharmacol"},{"key":"bibr36-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2015.04.004"},{"key":"bibr37-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/954136"},{"key":"bibr38-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1246-y"},{"key":"bibr39-0960327118758382","first-page":"32","volume":"20","author":"Hirooka Y","year":"2010","journal-title":"Clin Calcium"},{"key":"bibr40-0960327118758382","doi-asserted-by":"publisher","DOI":"10.4103\/0973-7847.70902"},{"key":"bibr41-0960327118758382","doi-asserted-by":"publisher","DOI":"10.5152\/eajm.2011.07"},{"key":"bibr42-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02064-5"},{"key":"bibr43-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/65.2.166"},{"key":"bibr44-0960327118758382","volume-title":"Cytokines. Cellular and Molecular Immunology","author":"Abbas AK","year":"1994"},{"key":"bibr45-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(86)90052-9"},{"key":"bibr46-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00219.2003"},{"key":"bibr47-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(200003)190:4<489::AID-PATH534>3.0.CO;2-V"},{"key":"bibr48-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1177\/019262339602400206"},{"key":"bibr49-0960327118758382","first-page":"89","volume":"9","author":"Fey GH","year":"1990","journal-title":"Prog Liver Dis"},{"key":"bibr50-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1990.tb19222.x"},{"key":"bibr51-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1989.tb24023.x"},{"key":"bibr52-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1995.1125"},{"key":"bibr53-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2009.04.010"},{"key":"bibr54-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1177\/039463201002300105"},{"key":"bibr55-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114643"},{"key":"bibr56-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.753"},{"key":"bibr57-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.04.042"},{"key":"bibr58-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115821"},{"key":"bibr59-0960327118758382","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1997.8126"},{"key":"bibr60-0960327118758382","first-page":"2014","volume":"696383","author":"Rocha SW","year":"2014","journal-title":"Mediators Inflamm"},{"key":"bibr61-0960327118758382","doi-asserted-by":"publisher","DOI":"10.3724\/SP.J.1263.2012.04011"},{"key":"bibr62-0960327118758382","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0022-3565(25)29666-5","volume":"187","author":"Mitchell JR","year":"1973","journal-title":"J Pharmacol Exp Ther"}],"container-title":["Human &amp; Experimental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0960327118758382","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0960327118758382","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0960327118758382","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:49:20Z","timestamp":1777448960000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0960327118758382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,14]]},"references-count":62,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1177\/0960327118758382"],"URL":"https:\/\/doi.org\/10.1177\/0960327118758382","relation":{},"ISSN":["0960-3271","1477-0903"],"issn-type":[{"value":"0960-3271","type":"print"},{"value":"1477-0903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,14]]}}}