title: Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory response, but not apoptosis in mouse: the prevention of curcumin.
abstract: This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling.
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Demei
authors.initials: D
authors.lastname: Xu
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Hu
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Chuanyang
authors.initials: C
authors.lastname: Su
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Xia
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Juanli
authors.initials: J
authors.lastname: Fu
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Duo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Du
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Erqun
authors.initials: E
authors.lastname: Song
authors.affiliation: Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China. Electronic address: songyangwenrong@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D016227:Benzoquinones / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D003474:Curcumin / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced*; D015850:Interleukin-6 / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D016328:NF-kappa B / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis
chemical_list: D016227:Benzoquinones; D006843:Hydrocarbons, Chlorinated; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; C000591600:tetrachlorobenzoquinone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020169:Caspases; D003474:Curcumin
keywords: Antioxidant; Hepatoprotection; Inflammation; NF-κB; TCBQ; TNF-α