{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:59:08Z","timestamp":1785214748017,"version":"3.55.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>Cisplatin, a widely used anticancer agent, has adverse effects on normal tissues during cancer treatment. This study aimed to investigate the use of harmine, a plant \u03b2-carboline alkaloid, against pathways associated with ROS-induced apoptosis in the livers of mice administered with cisplatin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>Twenty-four male Balb\/c mice were randomly assigned to four groups (n = 6): (1) control group received daily intraperitoneal injections of saline for four days, (2) harmine group (15 mg\/kg, intraperitoneally, daily for 4 days), (3) cisplatin group (5.5 mg\/kg, intraperitoneally, one injection), and (4) cisplatin + harmine co-administration group. After sacrificing the animals under deep anesthesia, blood and liver tissue samples were collected for biochemical and molecular experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings\/Results:<\/jats:title>\n                    <jats:p>\n                      Cisplatin significantly elevated histopathological criteria (both qualitative and quantitative), levels of enzyme activity, malondialdehyde, nitric oxide, ROS, and apoptosis, and decreased glutathione, superoxide dismutase, and total antioxidant capacity. However, these factors were improved in the co-administration group compared to the cisplatin group. Furthermore, cisplatin treatment significantly upregulated\n                      <jats:italic toggle=\"yes\">caspase-8, BAX, p53, caspase-3, TNF-\u03b1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">NF-\u03baB<\/jats:italic>\n                      gene expression, while downregulating\n                      <jats:italic toggle=\"yes\">BCL-2<\/jats:italic>\n                      . Co-administration with harmine led to significant changes in gene expression relative to the cisplatin group. Cisplatin notably increased protein levels of caspase-8, BAX, and TNF-\u03b1, but these levels were significantly reduced in the co-treatment group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and implications:<\/jats:title>\n                    <jats:p>Harmine effectively ameliorates cisplatin-induced hepatitis by suppressing ROS production, thereby reducing intrinsic, extrinsic, and inflammation-induced apoptosis. These findings suggest that the antioxidant and anti-inflammatory properties of Harmine play a key role in its hepatoprotective actions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/rps.rps_194_25","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:00:20Z","timestamp":1785124820000},"page":"452-465","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Harmine reduces ROS-mediated hepatotoxicity in a cisplatin mouse model"],"prefix":"10.4103","volume":"21","author":[{"given":"Cyrus","family":"Jalili","sequence":"first","affiliation":[{"name":"Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Akhshi","sequence":"additional","affiliation":[{"name":"Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran"},{"name":"Department of Nanobiotechnology, Faculty of Strategic Sciences and Technologies, Razi University, Kermanshah, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Mohebi","sequence":"additional","affiliation":[{"name":"Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Touraj","family":"Zamir-Nasta","sequence":"additional","affiliation":[{"name":"Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Tabandeh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran"},{"name":"Stem Cells and Transgenic Technology Research Center, Shahid Chamran University of Ahvaz, Ahvaz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojtaba","family":"Esmaeli","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Ravankhah","sequence":"additional","affiliation":[{"name":"Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Ghanbari","sequence":"additional","affiliation":[{"name":"Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"19","key":"R1-20260728","doi-asserted-by":"crossref","first-page":"6645","DOI":"10.1039\/C8DT00838H","article-title":"The side effects of platinum-based chemotherapy drugs: a review for chemists","volume":"47","author":"Oun","year":"2018","journal-title":"Dalton Trans"},{"key":"R2-20260728","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.biopha.2017.09.083","article-title":"Protective effect of Schisandra chinensis bee pollen extract on liver and kidney injury induced by cisplatin in rats","volume":"95","author":"Huang","year":"2017","journal-title":"Biomed Pharmacother"},{"issue":"2","key":"R3-20260728","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3390\/biomedicines5020018","article-title":"The protective effects of p-coumaric acid on acute liver and kidney damages induced by cisplatin","volume":"5","author":"Ekinci","year":"2017","journal-title":"Biomedicines"},{"issue":"3","key":"R4-20260728","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2131\/jts.44.167","article-title":"Astragaloside IV protects against cisplatin-induced liver and kidney injury via autophagy-mediated inhibition of NLRP3 in rats","volume":"44","author":"Qu","year":"2019","journal-title":"J Toxicol Sci"},{"issue":"1","key":"R5-20260728","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s11033-020-06111-0","article-title":"Possible protective activity of N-acetyl cysteine against cisplatin-induced hepatotoxicity in rats","volume":"48","author":"Co\u015fkun","year":"2021","journal-title":"Mol Biol Rep"},{"key":"R6-20260728","doi-asserted-by":"crossref","first-page":"119485","DOI":"10.1016\/j.lfs.2021.119485","article-title":"The protective effect of protocatechuic acid on hepatotoxicity induced by cisplatin in mice","volume":"277","author":"Habib","year":"2021","journal-title":"Life Sci"},{"issue":"4","key":"R7-20260728","doi-asserted-by":"crossref","first-page":"414","DOI":"10.4103\/1735-5362.319579","article-title":"Protective effect of gallic acid on nicotine-induced testicular toxicity in mice","volume":"16","author":"Jalili","year":"2021","journal-title":"Res Pharm Sci"},{"issue":"5","key":"R8-20260728","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/08941939.2019.1656309","article-title":"Acacetin alleviates hepatitis following renal ischemia-reperfusion in male Balb\/C mice by antioxidants regulation and inflammatory markers suppression","volume":"34","author":"Jalili","year":"2021","journal-title":"J Invest Surg"},{"key":"R9-20260728","first-page":"2018","article-title":"Lycium europaeum extract: a new potential antioxidant source against cisplatin-induced liver and kidney injuries in mice","author":"Rjeibi","year":"2018","journal-title":"Oxid Med Cell Longevity"},{"issue":"1","key":"R10-20260728","doi-asserted-by":"crossref","first-page":"13979","DOI":"10.1038\/s41598-021-93196-7","article-title":"Synergistic protective effects of lycopene and N-acetylcysteine against cisplatin-induced hepatorenal toxicity in rats","volume":"11","author":"Elsayed","year":"2021","journal-title":"Sci Rep"},{"issue":"22","key":"R11-20260728","doi-asserted-by":"crossref","first-page":"7815","DOI":"10.3390\/molecules27227815","article-title":"Rosmarinic acid prevents cisplatin-induced liver and kidney injury by inhibiting inflammatory responses and enhancing total antioxidant capacity, thereby activating the Nrf2 signaling pathway","volume":"27","author":"Xiang","year":"2022","journal-title":"Molecules"},{"issue":"2","key":"R12-20260728","first-page":"245","article-title":"Thymoquinone could increase the efficacy of tamoxifen induced apoptosis in human breast cancer cells: an in vitro study","volume":"18","author":"Ganji-Harsini","year":"2016","journal-title":"Cell J"},{"issue":"6","key":"R13-20260728","doi-asserted-by":"crossref","first-page":"541","DOI":"10.4103\/1735-5362.301339","article-title":"Harmine protects mercuric chloride kidney-induced injury by antioxidant activity in male mice: a biochemical and histological study","volume":"15","author":"Jalili","year":"2020","journal-title":"Res Pharm Sci"},{"issue":"9","key":"R14-20260728","first-page":"638","article-title":"Protective effects of subchronic caffeine administration on cisplatin-induced urogenital toxicity in male mice","volume":"50","author":"Khazaei","year":"2012","journal-title":"Indian J Exp Biol"},{"issue":"3","key":"R15-20260728","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.3390\/ijms23031532","article-title":"Pharmacological effects of cisplatin combination with natural products in cancer chemotherapy","volume":"23","author":"Dasari","year":"2022","journal-title":"Int J Mol Sci"},{"key":"R16-20260728","doi-asserted-by":"crossref","first-page":"152805","DOI":"10.1016\/j.phymed.2018.12.028","article-title":"Celastrol, a plant-derived triterpene, induces cisplatin-resistance nasopharyngeal carcinoma cancer cell apoptosis though ERK1\/2 and p38 MAPK signaling pathway","volume":"58","author":"Hsieh","year":"2019","journal-title":"Phytomedicine"},{"key":"R17-20260728","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.phymed.2017.05.007","article-title":"Galangin ameliorates cisplatin-induced nephrotoxicity in vivo by modulation of oxidative stress, apoptosis and inflammation through interplay of MAPK signaling cascade","volume":"34","author":"Tomar","year":"2017","journal-title":"Phytomedicine"},{"issue":"A","key":"R18-20260728","doi-asserted-by":"crossref","first-page":"766","DOI":"10.3889\/oamjms.2021.6654","article-title":"Alkaloids of Peganum harmala L. and their pharmacological activity","volume":"9","author":"Doskaliyev","year":"2021","journal-title":"Open Access Maced J Med Sci"},{"issue":"3","key":"R19-20260728","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s11224-022-01886-3","article-title":"In vitro antioxidant activities of five \u03b2-carboline alkaloids, molecular docking, and dynamic simulations","volume":"33","author":"Senhaji","year":"2022","journal-title":"Struct Chem"},{"issue":"3","key":"R20-20260728","first-page":"13","article-title":"Harmine mitigates liver injury induced by mercuric chloride via the inhibition of oxidative stress","volume":"8","author":"Jalili","year":"2021","journal-title":"Res J Pharmacogn"},{"issue":"7","key":"R21-20260728","first-page":"e202402953","article-title":"Bioactivities and structure-activity relationships of harmine and its derivatives: a review. Chem","volume":"22","author":"Liu","year":"2025","journal-title":"Biodivers"},{"issue":"2","key":"R22-20260728","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1007\/s11101-024-09978-0","article-title":"The anticancer properties of harmine and its derivatives","volume":"24","author":"Timbilla","year":"2025","journal-title":"Phytochem Rev"},{"issue":"4","key":"R23-20260728","doi-asserted-by":"crossref","first-page":"417","DOI":"10.4103\/1735-5362.350242","article-title":"Harmine mitigates cisplatin-induced renal injury in male mice through antioxidant, anti-inflammatory, and anti-apoptosis effects","volume":"17","author":"Ghanbari","year":"2022","journal-title":"Res Pharm Sci"},{"key":"R24-20260728","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4103\/ijpvm.IJPVM_85_18","article-title":"Effect of harmine on nicotine-induced kidney dysfunction in male mice","volume":"10","author":"Salahshoor","year":"2019","journal-title":"Int J Prev Med"},{"key":"R25-20260728","doi-asserted-by":"crossref","first-page":"111670","DOI":"10.1016\/j.biopha.2021.111670","article-title":"Captopril downregulates expression of Bax\/cytochrome C\/caspase-3 apoptotic pathway, reduces inflammation and oxidative stress in cisplatin-induced acute hepatic injury","volume":"139","author":"Eid","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"R26-20260728","doi-asserted-by":"crossref","first-page":"111538","DOI":"10.1016\/j.intimp.2024.111538","article-title":"Harmine ameliorates CCl4-induced acute liver injury through suppression of autophagy and inflammation","volume":"129","author":"Ma","year":"2024","journal-title":"Int Immunopharmaco"},{"issue":"11","key":"R27-20260728","doi-asserted-by":"crossref","first-page":"10509","DOI":"10.1074\/jbc.M413865200","article-title":"Cisplatin inactivation of caspases inhibits death ligand-induced cell death in vitro and fulminant liver damage in mice","volume":"280","author":"Shin","year":"2005","journal-title":"J Biol Chem"},{"key":"R28-20260728","doi-asserted-by":"crossref","first-page":"109245","DOI":"10.1016\/j.abb.2022.109245","article-title":"Reprint of: tissue sulfhydryl groups","volume":"726","author":"Ellman","year":"2022","journal-title":"Arch Biochem Biophys"},{"issue":"2","key":"R29-20260728","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4103\/1735-5362.335178","article-title":"Royal jelly protects dichlorvos liver-induced injury in male Wistar rats","volume":"17","author":"Jalili","year":"2022","journal-title":"Res Pharm Sci"},{"issue":"11","key":"R30-20260728","first-page":"1382","article-title":"The investigation of the effect of fraxin on hepatotoxicity induced by cisplatin in rats","volume":"23","author":"Ekinci-Akdemir","year":"2020","journal-title":"Iran J Basic Med Sci"},{"issue":"22","key":"R31-20260728","doi-asserted-by":"crossref","first-page":"33774","DOI":"10.1007\/s11356-022-18626-z","article-title":"Centella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxidative stress, inflammation, and apoptosis","volume":"29","author":"Ferah","year":"2022","journal-title":"Environ Sci Pollut Res Int"},{"key":"R32-20260728","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.fct.2018.05.001","article-title":"Summer savory (Satureja hortensis L.) extract: phytochemical profile and modulation of cisplatin-induced liver, renal and testicular toxicity","volume":"118","author":"Boroja","year":"2018","journal-title":"Food Chem Toxicol"},{"key":"R33-20260728","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.2147\/DDDT.S191240","article-title":"Neuroprotective effect of N-acetylcysteine against cisplatin-induced toxicity in rat brain by modulation of oxidative stress and inflammation","volume":"13","author":"Abdel-Wahab","year":"2019","journal-title":"Drug Des Devel Ther"},{"issue":"3","key":"R34-20260728","doi-asserted-by":"crossref","first-page":"e00788","DOI":"10.1002\/prp2.788","article-title":"Alleviation of cisplatin-induced hepatotoxicity by gliclazide: involvement of oxidative stress and caspase-3 activity","volume":"9","author":"Taghizadeh","year":"2021","journal-title":"Pharmacol Res Perspect"},{"key":"R35-20260728","doi-asserted-by":"crossref","first-page":"173168","DOI":"10.1016\/j.ejphar.2020.173168","article-title":"A novel effect of aprepitant: protection for cisplatin-induced nephrotoxicity and hepatotoxicity","volume":"880","author":"Un","year":"2020","journal-title":"Eur J Pharmaco"},{"key":"R36-20260728","doi-asserted-by":"crossref","first-page":"112328","DOI":"10.1016\/j.biopha.2021.112328","article-title":"The role of natural antioxidants in cisplatin-induced hepatotoxicity","volume":"144","author":"Abd","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"R37-20260728","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2147\/JEP.S267383","article-title":"Advances in our understanding of the molecular mechanisms of action of cisplatin in cancer therapy","volume":"13","author":"Tchounwou","year":"2021","journal-title":"J Exp Pharmacol"},{"issue":"5","key":"R38-20260728","first-page":"4049","article-title":"Protective effect of dexpanthenol against cisplatin-induced hepatotoxicity","volume":"16","author":"Bilgic","year":"2018","journal-title":"Exp Ther Med"},{"issue":"5","key":"R39-20260728","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1016\/j.sjbs.2022.01.052","article-title":"Hesperidin ameliorates cisplatin-induced hepatotoxicity and attenuates oxidative damage, cell apoptosis, and inflammation in rats","volume":"29","author":"Aboraya","year":"2022","journal-title":"Saudi J Biol Sci"},{"issue":"13","key":"R40-20260728","doi-asserted-by":"crossref","first-page":"20895","DOI":"10.18632\/oncotarget.14947","article-title":"Resveratrol induces mitochondria-mediated, caspase-independent apoptosis in murine prostate cancer cells","volume":"8","author":"Kumar","year":"2017","journal-title":"Oncotarget"},{"issue":"3","key":"R41-20260728","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/febs.14186","article-title":"Bax, Bak and beyond-mitochondrial performance in apoptosis","volume":"285","author":"Pe\u00f1a-Blanco","year":"2018","journal-title":"FEBS J"},{"key":"R42-20260728","doi-asserted-by":"crossref","first-page":"116607","DOI":"10.1016\/j.lfs.2019.116607","article-title":"Targeting of oxidative stress and inflammation through ROS\/NF-kappaB pathway in phosphine-induced hepatotoxicity mitigation","volume":"232","author":"Aminjan","year":"2019","journal-title":"Life Sci"},{"issue":"9","key":"R43-20260728","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.3390\/antiox12091653","article-title":"Oxidative stress in liver pathophysiology and disease","volume":"12","author":"Allameh","year":"2023","journal-title":"Antioxidants"},{"issue":"19","key":"R44-20260728","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.3390\/molecules26196084","article-title":"Antioxidant and anti-inflammatory effects of Peganum harmala extracts: an in vitro and in vivo study","volume":"26","author":"Abbas","year":"2021","journal-title":"Molecules"},{"issue":"3","key":"R45-20260728","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.bbrc.2017.05.126","article-title":"Harmine is an inflammatory inhibitor through the suppression of NF-\u03baB signaling","volume":"489","author":"Liu","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"R46-20260728","first-page":"34","article-title":"The role of harmine in up-regulating p53 gene expression and inducing apoptosis in MCF-7 cell line","volume":"11","author":"Roshankhah","year":"2020","journal-title":"Middle East J Cancer"},{"issue":"4","key":"R47-20260728","first-page":"324","article-title":"Harmine exhibits anti-apoptotic properties and reduces diabetes-induced testicular damage caused by streptozotocin in rats","volume":"51","author":"Ghanbari","year":"2024","journal-title":"Korean J Fertil Steril"},{"issue":"1","key":"R48-20260728","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1749-8546-6-11","article-title":"Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanoma","volume":"6","author":"Hamsa","year":"2011","journal-title":"Chin Med"}],"container-title":["Research in Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.4103\/RPS.RPS_194_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:02:48Z","timestamp":1785211368000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.4103\/RPS.RPS_194_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/rps.rps_194_25","relation":{},"ISSN":["1735-5362","1735-9414"],"issn-type":[{"value":"1735-5362","type":"print"},{"value":"1735-9414","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-10-06","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-30","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}