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.
Highlights
Total parenteral nutrition (TPN) is a method for providing nutrients, such as glucose, amino acids, lipids, added vitamins and dietary minerals, to patients who are unable to sustain adequate nutrition by standard enteral means, namely, those who suffer from gastrointestinal disorders
According to Loff et al and Shamir et al, injury to liver acinar Zone 3, which is composed of hepatocytes located around the hepatic venule that are mainly involved in the production of bile salt, was found in TPN related hepatitis in animal models [12,13]
The most significant effect was observed in the group of TPN rats that received glycyrrhizin (10 mg/kg) pretreatment, as the ALT and AST concentrations in the serum of these rats were restored to the levels of the saline-control group
Summary
Total parenteral nutrition (TPN) is a method for providing nutrients, such as glucose, amino acids, lipids, added vitamins and dietary minerals, to patients who are unable to sustain adequate nutrition by standard enteral means, namely, those who suffer from gastrointestinal disorders. Previous studies demonstrated three possible routes of pathogenesis for chronic TPN-induced hepatitis: direct toxic effect of detergent-like bile salts [8,9,10,11,12,13,14], increasing oxidative stress [15,16,17,18,19,20] and hepatocyte apoptosis [21,22,23]. According to Loff et al and Shamir et al, injury to liver acinar Zone 3, which is composed of hepatocytes located around the hepatic venule that are mainly involved in the production of bile salt, was found in TPN related hepatitis in animal models [12,13]. TPN-related hepatic injury in Zone 3 might be a typical feature for the direct toxic effect of the bile salt [13,14]
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