title: Glycyrrhizin represses total parenteral nutrition-associated acute liver injury in rats by suppressing endoplasmic reticulum stress.
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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, National Yang-Ming University Hospital, I-Lan 26042, Taiwan. thtsai@ym.edu.tw.
authors.forename: Jai-Jen
authors.initials: JJ
authors.lastname: Tsai
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.forename: Kam-Fai
authors.initials: KF
authors.lastname: Lee
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001663:Bilirubin / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D019695:Glycyrrhizic Acid / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology / Q000209:etiology*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D026361:Reactive Nitrogen Species; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014280:Triglycerides; D051742:Transcription Factor CHOP; C002744:3-nitrotyrosine; D014443:Tyrosine; D019695:Glycyrrhizic Acid; D052247:Nitric Oxide Synthase Type II; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D001663:Bilirubin