Elsevier

Toxicology

Volume 232, Issues 1–2, 22 March 2007, Pages 50-56
Toxicology

Protective effects of echinacoside on carbon tetrachloride-induced hepatotoxicity in rats

https://doi.org/10.1016/j.tox.2006.12.013Get rights and content

Abstract

The aim of this study was to investigate the possible protective effects of echinacoside, one of the phenylethanoids isolated from the stems of Cistanches salsa, a Chinese herbal medicine, on the free radical damage of liver caused by carbon tetrachloride in rats. Treatment of rats with carbon tetrachloride produced severe liver injury, as demonstrated by dramatic elevation of serum ALT, AST levels and typical histopathological changes including hepatocyte necrosis or apoptosis, haemorrhage, fatty degeneration, etc. In addition, carbon tetrachloride administration caused oxidative stress in rats, as evidenced by increased reactive oxygen species (ROS) production and MDA concentrations in the liver of rats, along with a remarkable reduction in hepatic SOD activity and GSH content. However, simultaneous treatment with echinacoside (50 mg/kg, intraperitoneally) significantly attenuated carbon tetrachloride-induced hepatotoxicity. The results showed that serum ALT, AST levels and hepatic MDA content as well as ROS production were reduced dramatically, and hepatic SOD activity and GSH content were restored remarkably by echinacoside administration, as compared to the carbon tetrachloride-treated rats. Moreover, the histopathological damage of liver and the number of apoptotic hepatocytes were also significantly ameliorated by echinacoside treatment. It is therefore suggested that echinacoside can provide a definite protective effect against acute hepatic injury caused by CCl4 in rats, which may mainly be associated with its antioxidative effect.

Introduction

Drug/chemicals-induced liver injury, also known as toxic hepatopathy, is a major clinical problem. It is showed by epidemiological studies that the prevalence of drug/chemicals-induced hepatopathy went up over the past decades especially in the developing countries (Bissel et al., 2001, Larrey, 2000, Lee, 2003). Despite that extensive studies have been made for decades, the precise mechanisms underlying drug/chemicals-induced liver injury are still unclear and remain controversial. And there is still lack of effective therapeutic strategies or specific medicines for such liver diseases. Recent studies indicated that oxidative stress might be a pivotal originating factor in the pathogenesis of the liver diseases including drug-induced hepatic damage, alcoholic hepatitis, and viral hepatitis or ischemic liver injury (Albano, 2002, Amin and Hamza, 2005, Jaeschke et al., 2002). Over production of free radicals are toxic to hepatocytes and initiate reactive oxygen species (ROS)-mediated cascade causing hepatocyte death, leading to acute hepatic damage (Jaeschke, 2000, Gutteridge, 1993, Pessayre, 1995, Sies, 1991). Therefore, antioxidative treatment was proposed to be a potential means of preventing or attenuating toxic liver injury (Hensley et al., 2000, Higuchi and Gores, 2003, Kaplowitz, 2002). However, the effects of most antioxidants against acute liver damage are not satisfactory enough to apply into clinical situations.

Echinacoside (Fig. 1) is one of the phenylethanoids isolated from the stems of Cistanches salsa, a Chinese herbal medicine, which is an important crude drug used both as an antisenium and antifatigue agent (Deng et al., 2004, Xiong et al., 1996). Several phenylethanoids have been shown to possess free radical scavenging properties and protect oxidative stress-induced toxic injuries (Deng et al., 2004, Gao et al., 1999). In the present study we aimed to investigate the potential effects of echinacoside in reducing oxidative stress, and improving histopathological abnormality in the liver of rats treated with CCl4 that not only could provide some helpful information for the therapy or prevention of such liver disease, but might promote the understanding of its mechanisms, especially the role of free radicals or oxidative stress in the pathogenesis of acute toxic liver injury.

Section snippets

Chemicals and reagents

Echinacoside from C. salsa was kindly supplied by Peking University Modern Research Center for Traditional Chinese Medicine. The purity of the compounds was shown to be more than 95% on high-performance liquid chromatography (HPLC). The TUNEL assay kit was obtained from Roche Diagnostics Company (Germany). PBN was purchased from Sigma Chemical Co., USA. All other reagents or drugs were of analytical grade.

Animals and treatments

Twenty-four adult male Sprague–Dawley rats weighing 200–250 g obtained from Peking

Effect of echinacoside on serum ALT, AST levels

It showed that serum ALT and AST levels were significantly elevated at 24 h following CCl4 administration to rats while simultaneous echinacoside treatment decreased remarkably the levels of serum ALT, AST in the liver of CCl4-treated rats, although the enzyme levels were still higher than in the control rats.

Effect of echinacoside on hepatic SOD, MDA and GSH contents

The results indicated that CCl4 exposure increased MDA concentrations but decreased SOD activities and GSH contents markedly in the liver of rats, as compared with the control rats,

Discussion

The aim of the present study was to investigate the potential hepatoprotective effects of echinacoside on the free radical damage of liver caused by carbon tetrachloride in rats. Liver is well known to be the major organ responsible for the metabolism of drugs and toxic chemicals, and therefore is the primary target organ for nearly all the toxic chemicals (Bissel et al., 2001, Larrey, 2000, Lee, 2003). Various pharmacological or chemical substances are known to cause hepatic injuries, such as

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