title: Activation of the Nrf2 Signaling Pathway Involving KLF9 Plays a Critical Role in Allicin Resisting Against Arsenic Trioxide-Induced Hepatotoxicity in Rats.
abstract: Arsenic trioxide (As2O3) is both the most prevalent, naturally occurring inorganic arsenical threatening human health and an efficient therapeutic for acute promyelocytic leukemia. Regretfully, As2O3-treated cancer patients often suffer from hepatotoxicity. While effective antioxidant and anticarcinogenic actions of allicin have previously been demonstrated, studies indicating how allicin affects As2O3-induced hepatotoxicity and arsenic accumulation are lacking. Our study, for the first time, elaborates potential details of the hepatoprotective mechanisms of allicin against As2O3-induced liver injury. Wistar rats were administrated allicin (30 mg/kg) 1 h before As2O3(3 mg/kg) by daily gavage for 2 weeks. Our results indicate that allicin ameliorated As2O3-induced liver dysfunction, oxidative stress, and arsenic accumulation in the liver. Meanwhile, allicin decreased NF-κB level and upregulated expression of proteins reduced by As2O3including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1, and Krüppel-like factor 9 (KLF9). In addition, allicin promoted B cell lymphoma-extra large expression and suppressed B cell lymphoma-2-associated X protein levels regulated by As2O3. However, neither allicin nor As2O3affected cytochrome P450 2E1 mRNA expression. In conclusion, allicin attenuated As2O3-induced hepatotoxicity by activating the Nrf2 signaling pathway involving KLF9 to inhibit oxidative stress and apoptosis. Our findings elucidate a detailed mechanism by which allicin provides protection against As2O3-induced liver injury and support its potential role as an adjunctive therapy for patients suffering from chronic arsenic exposure.
authors: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, China.
authors: Daqian
authors: D
authors: Yang
authors: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, China.
authors: Zhanjun
authors: Z
authors: Lv
authors: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, China.
authors: Haili
authors: H
authors: Zhang
authors: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, China.
authors: Biying
authors: B
authors: Liu
authors: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, China.
authors: Huijie
authors: H
authors: Jiang
authors: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, China.
authors: Xiao
authors: X
authors: Tan
authors: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, China.
authors: Jingjing
authors: J
authors: Lu
authors: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, China.
authors: Ruiqi
authors: R
authors: Baiyun
authors: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, China. zhangzhigang@neau.edu.cn.
authors: Zhigang
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001151:Arsenic / Q000097:blood / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D004220:Disulfides; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000633:toxicity; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013441:Sulfinic Acids / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001152:Arsenicals; D004220:Disulfides; D051741:Kruppel-Like Transcription Factors; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D010087:Oxides; D013441:Sulfinic Acids; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C077017:Klf9 protein, rat; C006452:allicin; D019392:Cytochrome P-450 CYP2E1; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D001151:Arsenic; D000077237:Arsenic Trioxide
keywords: Allicin; Arsenic trioxide; Krüppel-like factor 9; Nuclear factor erythroid 2-related factor 2; Oxidative stress