Activation of the Nrf2 Signaling Pathway Involving KLF9 Plays a Critical Role in Allicin Resisting Against Arsenic Trioxide-Induced Hepatotoxicity in Rats

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• 作者：Daqian Yang ; Zhanjun Lv ; Haili Zhang ; Biying Liu…
• 关键词：Allicin ; Arsenic trioxide ; Oxidative stress ; Nuclear factor erythroid 2 ; related factor 2 ; Krüppel ; like factor 9
• 刊名：Biological Trace Element Research
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：176
• 期：1
• 页码：192-200
• 全文大小：
• 刊物主题：Biochemistry, general; Biotechnology; Nutrition; Oncology;
• 出版者：Springer US
• ISSN：1559-0720
• 卷排序：176

文摘

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 As₂O₃ including 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 As₂O₃ affected 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.