title: Improved Hepatoprotective Effect of Liposome-Encapsulated Astaxanthin in Lipopolysaccharide-Induced Acute Hepatotoxicity.
abstract: Lipopolysaccharide (LPS)-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST), a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA) apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group) were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10) for seven days and then were LPS-challenged (i.p., 5 mg/kg). The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), creatinine (CRE), hepatic malondialdehyde (MDA) and glutathione peroxidase (GSH-Px), IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS), suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day). Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity.
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, Taichung City 43302, Taiwan. chchiu@hk.edu.tw.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Chiu
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan. chunchao@tmu.edu.tw.|Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. chunchao@tmu.edu.tw.
authors.forename: Chun-Chao
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, Taichung City 43302, Taiwan. n404user@gmail.com.
authors.forename: Shiang-Ting
authors.initials: ST
authors.lastname: Lin
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, Taichung City 43302, Taiwan. ccchyau@sunrise.hk.edu.tw.
authors.forename: Charng-Cherng
authors.initials: CC
authors.lastname: Chyau
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, Taichung City 43302, Taiwan. ccchyau@hk.edu.tw.|Research Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan. ccchyau@hk.edu.tw.
authors.forename: Robert Y
authors.initials: RY
authors.lastname: Peng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D005343:Fibrinolytic Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008081:Liposomes; D016328:NF-kappa B; D053769:Nanocapsules; D020011:Protective Agents; D024341:Xanthophylls; D008315:Malondialdehyde; C005948:astaxanthine; D052247:Nitric Oxide Synthase Type II; D005978:Glutathione
keywords: Astaxanthin; antioxidant enzymes; hepatotoxicity; inflammation; liposome encapsulation