Protective effect of artemisinin on chronic alcohol induced-liver damage in mice

doi:10.1016/j.etap.2017.04.008

Environmental Toxicology and Pharmacology

Volume 52, June 2017, Pages 221-226

https://doi.org/10.1016/j.etap.2017.04.008 Get rights and content

Highlights

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Liver injury in mice was induced by administration of alcohol for 30 days.
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Artemisinin decreases the levels of AST, ALT and the liver weight index.
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Artemisinin alleviates liver injury induced by chronic alcohol consumption.
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Artemisinin showed a protective effect against chronic alcohol poisoning.

Abstract

The liver disease related to chronic alcohol consumption is one of the leading causes of death for alcoholics. The efficient drug to ameliorate the alcoholic liver injury was needed urgently. The present study was performed to investigate whether artemisinin possessed the protective effect against chronic alcohol consumption. 50 male Kunming mice were divided into 5 groups: control group (C): 10 ml/kg saline + 10 ml/kg saline, alcohol group (A): 10 ml/kg 56%(v/v) alcohol + 10 ml/kg saline, low dose group of artemisinin (L): 10 ml/kg 56%(v/v) alcohol + 30 mg/kg/day artemisinin, medium dose group of artemisinin (M): 10 ml/kg 56%(v/v) alcohol + 60 mg/kg/day artemisinin, high dose group of artemisinin (H): 10 ml/kg 56%(v/v) alcohol + 120 mg/kg/day artemisinin. Drugs were given orally every day. The general state of mice was observed and the levels of serum activities of AST and ALT were detected after treatment with drugs for 30 days. Besides, the liver weight index was calculated and histopathological analysis was performed. We successfully demonstrated that treatment with high dose of artemisinin significantly decreased the elevated levels of AST (p < 0.05) and ALT (p < 0.01) in plasma, as well as the liver weight index (p < 0.01). The loss of body weight, tissue injury, oedema and inflammatory cell infiltration in the hepatocytes were found in the A group. These symptoms were remarkably alleviated in animals treated with artemisinin. Artemisinin can inhibit the activation of NF-кB and the expression of inflammatory cytokines inducible nitric oxide synthase. Besides, it can also enhance the stability of liver cell membrane, and reduce the damage of liver cell membrane and liver cell. Artemisinin showed a protective effect against chronic alcohol poisoning and it has a great potential for the clinical application to treat the liver injury induced by alcohol.

Introduction

Alcoholism, a severe worldwide health problem, has caused many disorders including alcoholic fatty liver, alcoholic hepatitis, alcoholic fibrosis and alcoholic cirrhosis (Rong et al., 2012). It has been suggested that the liver could be severely damaged due to chronic alcohol intake (Kundua et al., 2008). The possible mechanisms of the alcohol-induced oxidative stress have been reported, including the change in redox state, production of acetaldehyde, mitochondrial injury, the mobilization of iron and the decrease of antioxidant enzymes (Giriwono et al., 2010). The oxidative stress and the generation of free radicals play critical roles in chronic alcohol induced-liver damage (Wang et al., 2012). More phenolic hydroxyl groups with hydrogen donor activity have been found which can inhibit the primary reaction of free radicals. It was also reported that the complement system showed a protective effect against alcohol-induced rat liver damage (Bykov et al., 2004). However, the clear pathogenetic mechanisms are still poorly understood.

Previous studies have shown that some natural plant products, such as Curcumin and Puerarin, possessed protective effects against the liver disorder induced by chronic alcohol intake. The main sources of biologically active compounds come from the natural plant products. Thus, the natural products with antioxidant activity become more and more attracted.

Artemisinin, isolated from the compositae plants Artemisia annua, is a sesquiterpene lactone secondary metabolite with an endoperoxide bridge (Kim et al., 2008). Artemisinin and its analogs have been used to treat malaria (Laia et al., 2005). In addition, it has been investigated that artemisinin possessed the potent anti-cancer activity in vitro (Singh and Lai, 2001, Singh and Lai, 2004, Efferth et al., 2004) and in vivo (Moore et al., 1995, Chen et al., 2004, Lai and Singh, 2006). Besides, it has been shown that artemisinin possessed the potential of anti-fibrosis and anti-inflammatory effects (Wong and Menendez, 1999). The possible effect of artemisinin in the regulation of inflammatory responses has been demonstrated (Tan et al., 1999).

However, no study has been carried out concerning the protective effects of artemisinin on chronic alcohol induced-liver damage yet. The present study was performed to investigate the possible effect of artemisinin on chronic alcohol induced-liver damage in mice. The results showed that artemisinin significantly ameliorated chronic alcohol-induced structural abnormalities in liver tissue and the serum levels AST and ALT.

Section snippets

Drugs and reagents

Artemisinin (Purity ≥ 99.5%, Molecular weight: 282.34, Cas number: 63968-64-9) was obtained from Aladdin chemistry Co. Ltd (Shanghai, China). The alcohol was purchased from Hongxing Co. Ltd (Beijing, China). The alanine aminotransferase (ALT) and aspartate transaminase (AST) reagent kit were purchased from Jiancheng Bio-engineering Institute (Nanjing, China). The arowana edible oil was purchased from Wilmar International Limited (Shenzhen, China).

Experimental animals

A total of 50 male KM mice (about 16–18 g) were

Body weight changes and liver weight index

The body weight changes during the experiment are shown in Fig. 1. Mice treated with alcohol alone showed lower body weight gain compared to those of the other groups. Moreover, the reduction of appetite and the less of activities were presented in A group's animals (Fig. 2). These data suggested that the A group animals was in poor health. Body weight in artemisinin-treated groups was increased compared to A group, especially in the H group.

The liver weight index, liver to body weight ratio,

Discussion

In the present study, chronic alcohol induced-liver damage in mice was established via treating animals with alcohol for 30 days. The decrease of body weight, elevation of liver weight index, increased serum AST and ALT levels, and inflammatory cell infiltration were found in mice after treatment with alcohol. The liver indicator and the serum aminotransferase activities were used to evaluate the liver functions. After treatment with alcohol, the liver cell membranes were damaged and then

Conflict of interest

The authors report no declarations of interest.

Acknowledgments

The present study was supported by the funds of the Chongqing Science and Technology Commission (no. cstc2016jcyjA0296) and the Fundamental Research Funds for the Central University (no. XDJK2014B024 and XDJK2016A015).

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Protective effect of artemisinin on chronic alcohol induced-liver damage in mice

Highlights

Abstract

Introduction

Section snippets

Drugs and reagents

Experimental animals

Body weight changes and liver weight index

Discussion

Conflict of interest

Acknowledgments

Int. Immunopharmacol.

Free Radic. Biol. Med.

Food Res. Int.

Eur. J. Pharmacol.

Cancer Lett.

Cancer Lett.

Chem. Biol. Interact.

Phytomedicine

Life Sci.