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Glycyrrhizin Represses Total Parenteral Nutrition-Associated Acute Liver Injury in Rats by Suppressing Endoplasmic Reticulum Stress
Division of Gastroenterology, Department of Medicine, National Yang-Ming University Hospital, I-Lan 26042, Taiwan
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
Department of Nursing, Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology Chiayi Campus, Chiayi 61363, Taiwan
Department of Pathology, Chang Gung Memorial Hospital at Chiayi, Chiayi 61363, Taiwan
Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan
Department of Education and Research, Taipei City Hospital, Taipei 10341, Taiwan
* Author to whom correspondence should be addressed.
Received: 22 April 2013; in revised form: 5 June 2013 / Accepted: 6 June 2013 / Published: 14 June 2013
Abstract: Total parenteral nutrition (TPN) is an artificial way to support daily nutritional requirements by bypassing the digestive system, but long-term TPN administration may cause severe liver dysfunction. Glycyrrhizin is an active component of licorice root that has been widely used to treat chronic hepatitis. The aim of this study is to investigate the hepatoprotective effect of glycyrrhizin on TPN-associated acute liver injury in vivo. Liver dysfunction was induced by intravenous infusion of TPN at a flow rate of 20 mL/kg/h for three h in Sprague Dawley rats. The rats were pretreated with Glycyrrhizin (1, 3 and 10 mg/kg intravenously). After receiving TPN or saline (control group) for three h, the rats were sacrificed, blood samples were collected for biochemical analyses and liver tissue was removed for histopathological and immunohistochemical examination. We found that aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB) and triglyceride (TG) levels were significantly increased in the TPN group without glycyrrhizin pretreatment and decreased in the glycyrrhizin-pretreated TPN group in a dose-dependent manner. The stained liver sections showed that glycyrrhizin relieved acute liver injury. The upregulation of serum protein biomarkers of reactive nitrogen species, including nitrotyrosine and inducible NO synthase (iNOS), were attenuated by glycyrrhizin pretreatment. Levels of endoplasmic reticulum (ER) stress factors, such as phosphorylation of JNK1/2, p38 MAPK and CHOP, were decreased by glycyrrhizin pretreatment. In summary, our results suggest that glycyrrhizin decreases TPN-associated acute liver injury factors by suppressing endoplasmic reticulum stress and reactive nitrogen stress.
Keywords: total parenteral nutrition (TPN); endoplasmic reticulum (ER); glycyrrhizin
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MDPI and ACS Style
Tsai, J.-J.; Kuo, H.-C.; Lee, K.-F.; Tsai, T.-H. Glycyrrhizin Represses Total Parenteral Nutrition-Associated Acute Liver Injury in Rats by Suppressing Endoplasmic Reticulum Stress. Int. J. Mol. Sci. 2013, 14, 12563-12580.
Tsai J-J, Kuo H-C, Lee K-F, Tsai T-H. Glycyrrhizin Represses Total Parenteral Nutrition-Associated Acute Liver Injury in Rats by Suppressing Endoplasmic Reticulum Stress. International Journal of Molecular Sciences. 2013; 14(6):12563-12580.
Tsai, Jai-Jen; Kuo, Hsing-Chun; Lee, Kam-Fai; Tsai, Tung-Hu. 2013. "Glycyrrhizin Represses Total Parenteral Nutrition-Associated Acute Liver Injury in Rats by Suppressing Endoplasmic Reticulum Stress." Int. J. Mol. Sci. 14, no. 6: 12563-12580.