title: Multi-targeted protection of acetaminophen-induced hepatotoxicity in mice by tannic acid.
abstract: Tannic acid (TA) is the polyphenol that has beneficial health effects against oxidative stress. However, the hepatoprotective effects of TA are still relatively unknown. In the present study, we evaluated the effects of TA on an acetaminophen (APAP)-induced hepatotoxicity model, which was established by administration of 400mg/kg of APAP. The levels of alanine transferase (ALT), aspartate transferase (AST), dendothelin-1 (ET-1), nitric oxide (NO) and malondialdehyde (MDA) in the APAP-induced hepatotoxicity mice were significantly increased (up to ~200%), while their levels were reduced by pretreatment with TA (25 and 50mg/kg) (P<0.05). The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the APAP-induced hepatotoxicity mice were significantly reduced (lower to ~65%), while their activities were increased by pretreatment with TA (25 and 50mg/kg) (P<0.05). In addition, pretreatment with oral TA (25 and 50mg/kg) for 3days before the APAP administration dose-dependently ameliorated changes in hepatic histopathology, suppressed overexpression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), c-fos, c-jun, NF-κB (p65) and caspase-3 (all P<0.05), downregulated bax and upregulated bcl-2, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) (all P<0.05) in the liver. These results indicate that TA exhibits significant hepatoprotective effects against APAP-induced hepatotoxicity and suggest that the hepatoprotective mechanisms of TA may be related to anti-oxidation, anti-inflammation and anti-apoptosis.
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei Medical University, No.361, Zhongshan East Road, Shijiazhuang 050017, Hebei, China.
authors.forename: Qiongtao
authors.initials: Q
authors.lastname: Song
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Fourth Hospital of Hebei Medical University, No.12, Jiankang Road, Shijiazhuang 050011, Hebei, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chu
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei, China. Electronic address: chuli0614@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chu
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D019332:Endothelin-1 / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013634:Tannins / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D019332:Endothelin-1; D018836:Inflammation Mediators; D013634:Tannins; D009569:Nitric Oxide; D000082:Acetaminophen; D008315:Malondialdehyde; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Acetaminophen; Anti-apoptosis; Anti-inflammation; Anti-oxidation; Tannic acid