Silymarin Prevents Restraint Stress-Induced Acute Liver Injury by Ameliorating Oxidative Stress and Reducing Inflammatory Response.

Sou Kim,Dong Yuk,Dal-Seok Oh,Tae Son,Young-Suk Jung,Ji Oh

doi:10.3390/molecules21040443

Abstract

Silymarin is a flavonoid extracted from the milk thistle Silybum marianum. It has been reported to prevent liver injuries induced by various chemicals or toxins. Our recent study suggested that silymarin induces hepatic synthesis of glutathione by increasing cysteine availability, which may consequently contribute to increased antioxidant capacity of the liver. In the present study, we investigated the effects of silymarin on acute liver injury induced by restraint stress. Silymarin (100 mg/kg) was orally administered to BALB/c mice every 12 h (3 times in total). After the last dose, mice were subjected to restraint stress for 6 h, and serum levels of aspartate and alanine aminotransferases, and hepatic levels of lipid peroxidation were determined. Hepatic levels of sulfur-containing metabolites such as methionine, S-adenosylmethionine, cysteine, and glutathione were also measured. The level of pro-inflammatory mediators in both liver and serum was determined. To study the mechanism of the effects of silymarin, we assessed Jun N-terminal kinase (JNK) activation and apoptotic signaling. Restraint stress induced severe oxidative stress and increased mRNA levels of pro-inflammatory mediators; both effects of restraint stress were significantly inhibited by silymarin. Moreover, administration of silymarin significantly prevented acute liver injury induced by restraint stress by blocking JNK activation and subsequently apoptotic signaling. In conclusion, these results suggest that the inhibition of restraint stress–induced liver injury by silymarin is due at least in part to its anti-oxidant activity and its ability to suppress the inflammatory response.

Highlights

Stress can disrupt physiological homeostasis and induce a number of psychological and physical disorders [1,2,3]
Silymarin supplementation reduced increase inthe serum enzyme activities by supplementation the increase in serum enzyme activities induced by restraint stress, restraint stress, markedly indicatingreduced that silymarin administration protected against restraint stress-induced indicating silymarin administration protected against restraint stress-induced acute liver injury
Considering that GSH is a potent endogenous antioxidant,we wehypothesized hypothesized that silymarin could prevent restraint stress–induced acuteinjury liver antioxidant, that silymarin could prevent restraint stress–induced acute liver injury by reducing oxidative by reducing oxidative stress. stress

Summary

Introduction

Stress can disrupt physiological homeostasis and induce a number of psychological and physical disorders [1,2,3]. Restraint stress increases susceptibility to xenobiotics [4,5], inhibits lipid and glucose metabolism [6,7], and provokes liver damage [8,9]. Excessive generation of reactive oxygen species (ROS) is the main contributor to stress-initiated diseases [9,10]. The liver is a major organ prone to oxidative stress-induced damage. On the basis of clinical observations, a correlation between hepatic disease and psychological stress has been proposed [11]. The authors have suggested that emotional stress worsens the symptoms of hepatic disorders and alters blood chemistry related to liver

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Conclusion