title: Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis.
abstract: Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST), inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides) and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α) and enhancement of interleukin-10 (IL-10). Meanwhile, it lowered malondialdehyde (MDA), nitric oxide (NO) and nuclear factor erythroid 2-related factor 2 (NRF-2) levels with restoration of glutathione (GSH), and glutathione peroxidase (GPx). Regarding mitogen-activated protein kinase (MAPK) pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinase (p-ERK1/2) in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.|Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab of Emirates.
authors.forename: Hany A
authors.initials: HA
authors.lastname: Omar
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
authors.forename: Wafaa R
authors.initials: WR
authors.lastname: Mohamed
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Hany H
authors.initials: HH
authors.lastname: Arab
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif 21974, Saudi Arabia.
authors.forename: El-Shaimaa A
authors.initials: el-SA
authors.lastname: Arafa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D002945:Cisplatin / Q000633:toxicity*; D047309:Flavones / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D047309:Flavones; D019253:Proto-Oncogene Proteins c-bcl-2; D012838:Silymarin; D014280:Triglycerides; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D008315:Malondialdehyde; D002784:Cholesterol; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; C059006:tangeretin; D002945:Cisplatin