Astaxanthin pretreatment attenuates acetaminophen-induced liver injury in mice

• Published in: International immunopharmacology 2017-04, Vol.45, p.26-33
• Main Authors: Zhang, Jingyao, Zhang, Simin, Bi, Jianbin, Gu, Jingxian, Deng, Yan, Liu, Chang
• Format: Article
• Language: English
• Subjects: Acetaminophen; Acetaminophen - toxicity; Alanine; Alanine transaminase; Alanine Transaminase - blood; Analgesics; Animals; Antioxidants; Antioxidants - therapeutic use; Apoptosis; Apoptosis - drug effects; Aspartate Aminotransferases - blood; Aspartate transaminase; Astaxanthin; c-Jun protein; Chemical and Drug Induced Liver Injury - drug therapy; Damage prevention; Diabetes mellitus; Dosage; Drug overdose; Extracellular signal-regulated kinase; Glutathione; Glutathione - metabolism; Hepatotoxicity; Immunomodulation; Inflammation; JNK Mitogen-Activated Protein Kinases - metabolism; JNK pathway; JNK protein; Lipid peroxidation; Lipid Peroxidation - drug effects; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver diseases; Liver injury; Male; MAP kinase; Mice; Mice, Inbred C57BL; Oils & fats; Olive oil; Overdose; Oxidative stress; Peritoneum; Peroxidation; Phosphorylation; Protein kinase; Proteins; Reactive oxygen species; Signal Transduction - drug effects; Superoxide dismutase; Survival; TNF Receptor-Associated Factor 2 - metabolism; Toxicity; Transcription factors; Tumor Necrosis Factor-alpha - metabolism; Xanthophylls - therapeutic use
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2017.01.028

Acetaminophen (APAP) is a conventional drug widely used in the clinic because of its antipyretic-analgesic effects. However, accidental or intentional APAP overdoses induce liver injury and even acute liver failure (ALF). Astaxanthin (ASX) is the strongest antioxidant in nature that shows preventive and therapeutic properties, such as ocular protection, anti-tumor, anti-diabetes, anti-inflammatory, and immunomodulatory effects. The aim of present study was to determine whether ASX pretreatment provides protection against APAP-induced liver failure. Male C57BL/6 mice were randomly divided into 7 groups, including control, oil, ASX (30mg/kg or 60mg/kg), APAP and APAP+ASX (30mg/kg or 60mg/kg) groups. Saline, olive oil and ASX were administered for 14days. The APAP and APAP+ASX groups were given a peritoneal injection of 700mg/kg or 300mg/kg APAP to determine the 5-day survival rate and for further observation, respectively. Blood and liver samples were collected to detect alanine transaminase (ALT), aspartate transaminase (AST), inflammation, oxidative stress and antioxidant systems, and to observe histopathologic changes and key proteins in the mitogen-activated protein kinase (MAPK) family. ASX pretreatment before APAP increased the 5-day survival rate in a dose-dependent manner and reduced the ALT, AST, hepatic necrosis, reactive oxygen species (ROS) generation, lipid peroxidation (LPO), oxidative stress and pro-inflammatory factors. ASX protected against APAP toxicity by inhibiting the depletion of glutathione (GSH) and superoxide dismutase (SOD). Administration of ASX did not change the expression of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and P38. However, phosphorylation of JNK, ERK and P38 was reduced, consistent with the level of tumor necrosis factor alpha (TNF-α) and TNF receptor-associated factor 2 (TRAF2). ASX provided protection for the liver against APAP hepatotoxicity by alleviating hepatocyte necrosis, blocking ROS generation, inhibiting oxidative stress, and reducing apoptosis by inhibiting the TNF-α-mediated JNK signal pathway and by phosphorylation of ERK and P38, which made sense in preventing and treating liver damage. •Astaxanthin is a fat-soluble xanthophyll with powerful antioxidant capacity.•Astaxanthin has anti-inflammatory and immunomodulatory effects.•Astaxanthin inhibits the inflammation in APAP induced liver injury.•Astaxanthin inhibits the oxidative stress in APAP induced liver injury.•Astaxan