title: Inflammatory stress potentiates emodin-induced liver injury in rats.
abstract: Herbal medicines containing emodin, widely used for the treatment of hepatitis in clinic, have been reported with hepatotoxicity in individuals. A modest inflammatory stress potentiating liver injury has been linked to the idiosyncratic drug-induced liver injury (IDILI). In this study, we investigated the hypothesis that lipopolysaccharide (LPS) interacts with emodin could synergize to cause liver injury in rats. Emodin (ranging from 20, 40, to 80 mg/kg), which is in the range of liver protection, was administered to rats, before LPS (2.8 mg/kg) or saline vehicle treatment. The biochemical tests showed that non-toxic dosage of LPS coupled with emodin caused significant increases of plasma ALT and AST activities as compared to emodin alone treated groups (P < 0.05). In addition, with LPS or emodin alone could not induce any changes in ALT and AST activity, as compared with the control group (0.5% CMC-Na treatment). Meanwhile, the plasma proinflammatory cytokines, TNF-α, IL-1β, and IL-6 increased significantly in the emodin/LPS groups compared to either emodin groups or the LPS (P < 0.05). Histological analysis showed that liver damage was only found in emodin/LPS cotreatmented rat livers samples. These results indicate that non-toxic dosage of LPS potentiates the hepatotoxicity of emodin. This discovery raises the possibility that emodin and herbal medicines containing it may induce liver injury in the inflammatory stress even in their therapeutic dosages.
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China.
authors.forename: Can
authors.initials: C
authors.lastname: Tu
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China ; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences , Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China ; School of Pharmacy, Shandong University of Traditional Chinese Medicine , Jinan, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China ; School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu, China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China.
authors.forename: Rui-Sheng
authors.initials: RS
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China ; Department of Traditional Chinese Medicine, Beijing Friendship Hospital of Capital Medical University , Beijing, China.
authors.forename: Ge-Liu-Chang
authors.initials: GL
authors.lastname: Jia
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China ; Department of Traditional Chinese Medicine, Beijing Friendship Hospital of Capital Medical University , Beijing, China.
authors.forename: Jing-Yao
authors.initials: JY
authors.lastname: Pang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China.
authors.forename: He-Rong
authors.initials: HR
authors.lastname: Cui
authors.affiliation: Department of Traditional Chinese Medicine, Beijing Friendship Hospital of Capital Medical University , Beijing, China.
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Ma
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China.
authors.forename: Xiao-He
authors.initials: XH
authors.lastname: Xiao
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital , Beijing, China.
authors.forename: Jia-Bo
authors.initials: JB
authors.lastname: Wang
keywords: emodin; hepatotoxicity; idiosyncratic drug-induced liver injury; lipopolysaccharide; proinflammatory mediators; therapeutic dosages