title: Taurine zinc solid dispersions enhance bile-incubated L02 cell viability and improve liver function by inhibiting ERK2 and JNK phosphorylation during cholestasis.
abstract: Dietary intakes of taurine and zinc are associated with decreased risk of liver disease. In this study, solid dispersions (SDs) of a taurine zinc complex on hepatic injury were examined in vitro using the immortalized human hepatocyte cell line L02 and in a rat model of bile duct ligation. Sham-operated and bile duct ligated Sprague-Dawley rats were treated with the vehicle alone or taurine zinc (40, 80, 160mg/kg) for 17days. Bile duct ligation significantly increased blood lipid levels, and promoted hepatocyte apoptosis, inflammation and compensatory biliary proliferation. In vitro, incubation with bile significantly reduced L02 cell viability; this effect was significantly attenuated by pretreatment with SP600125 (a JNK inhibitor) and enhanced when co-incubated with taurine zinc SDs. In vivo, administration of taurine zinc SDs decreased serum alanine aminotransferase and aspartate aminotransferase activities in a dose-dependent manner and attenuated the increases in serum total bilirubin, total cholesterol and low density lipoprotein cholesterol levels after bile duct ligation. Additionally, taurine zinc SDs downregulated the expression of interleukin-1β and inhibited the phosphorylation of Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase2 (ERK2) in the liver after bile duct ligation. Moreover, taurine zinc SDs had more potent blood lipid regulatory and anti-apoptotic effects than the physical mixture of taurine and zinc acetate. Therefore, we speculate that taurine zinc SDs protect liver function at least in part via a mechanism linked to reduce phosphorylation of JNK and ERK2, which suppresses inflammation, apoptosis and cholangiocyte proliferation during cholestasis.
authors: Lab of Traditional Chinese Medicine and Marine Drugs, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou 510275, Guangdong Province, China.
authors: Yu
authors: Y
authors: Wang
authors: Lab of Traditional Chinese Medicine and Marine Drugs, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou 510275, Guangdong Province, China.
authors: Xueting
authors: X
authors: Mei
authors: Lab of Traditional Chinese Medicine and Marine Drugs, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou 510275, Guangdong Province, China.
authors: Jingquan
authors: J
authors: Yuan
authors: Lab of Traditional Chinese Medicine and Marine Drugs, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou 510275, Guangdong Province, China.
authors: Xiaofang
authors: X
authors: Lai
authors: Lab of Traditional Chinese Medicine and Marine Drugs, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou 510275, Guangdong Province, China. Electronic address: Donghuixu007@163.com.
authors: Donghui
authors: D
authors: Xu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D001652:Bile Ducts / Q000601:surgery; D001663:Bilirubin / Q000097:blood; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002779:Cholestasis / Q000188:drug therapy; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D008026:Ligation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; D013654:Taurine; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019950:Mitogen-Activated Protein Kinase 1; D048670:MAP Kinase Kinase 4; D015032:Zinc; D001663:Bilirubin
keywords: Apoptosis; Bile duct ligation; C-Jun N-terminal kinase; Extracellular signal-regulated kinase2; Inflammation; Taurine zinc solid dispersions