Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.

Jingjing Li,Chuanyong Guo,Jing Yang,Yuanyuan Zheng,Chengfen Wang,Huawei Zhang,Weiqi Dai,Huerxidan Abudumijiti,Yujing Xia,Tong Liu,Qin Yin,Junshan Wang,Yingqun Zhou,Yuqing Zhou,Jianrong Wang,Zheng Zhou,Sainan Li,Kan Chen,Wenxia Lu,Rong Zhu,Wei Fan ,Jie Lü

doi:10.1371/journal.pone.0120440

Abstract

ObjectiveAstaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation.Materials and MethodsAutoimmune hepatitis was induced in in Balb/C mice using ConA (25 mg/kg), and astaxanthin was orally administered daily at two doses (20 mg/kg and 40 mg/kg) for 14 days before ConA injection. Levels of serum liver enzymes and the histopathology of inflammatory cytokines and other maker proteins were determined at three time points (2, 8 and 24 h). Primary hepatocytes were pretreated with astaxanthin (80 μM) in vitro 24 h before stimulation with TNF-α (10 ng/ml). The apoptosis rate and related protein expression were determined 24 h after the administration of TNF-α.ResultsAstaxanthin attenuated serum liver enzymes and pathological damage by reducing the release of inflammatory factors. It performed anti-apoptotic effects via the descending phosphorylation of Bcl-2 through the down-regulation of the JNK/p-JNK pathway.ConclusionThis research firstly expounded that astaxanthin reduced immune liver injury in ConA-induced autoimmune hepatitis. The mode of action appears to be downregulation of JNK/p-JNK-mediated apoptosis and autophagy.

Highlights

The liver, the largest digestive gland, is the center of energy metabolism in the body
The incidence of severe autoimmune hepatitis that develops into liver cirrhosis, liver failure or even death has dramatically increased in Europe, the United States and Asian countries in recent times [1,2]
We investigated the mechanism of action of astaxanthin in concanavalin A (ConA)-induced autoimmune hepatitis

Summary

Introduction

The liver, the largest digestive gland, is the center of energy metabolism in the body. Hepatitis is a condition characterized by inflammation of the liver and the presence of inflammatory cells in the liver tissue. Autoimmune hepatitis is a chronic disease caused by an abnormal immune response against liver cells. The incidence of severe autoimmune hepatitis that develops into liver cirrhosis, liver failure or even death has dramatically increased in Europe, the United States and Asian countries in recent times [1,2]. The etiology of this chronic disease is not fully understood [3]. This condition is therapeutically controlled by administration of glucocorticoid combined with azathioprine, side effects are experienced due to impaired immunity and a disturbed endocrine system [4]. The identification of effective and safe treatment options for autoimmune hepatitis is urgently required

Methods

Discussion

Conclusion