Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress

Abstract

Artichoke is a plant with antioxidant properties. In this study, we investigated the effect of artichoke extract pretreatment on carbon tetrachloride (CCl₄)-induced oxidative stress and hepatotoxicity. Rats were given artichoke leaf extract (1.5 g/kg/day) by gavage for 2 weeks and after then CCl₄ (1 ml/kg; i.p.) was applied. All rats were killed 24 h after the CCl₄ injection. CCl₄ administration resulted in hepatic necrosis and significant increases in plasma transaminase activities as well as hepatic malondialdehyde (MDA) and diene conjugate (DC) levels in the liver of rats. Glutathione (GSH) and vitamin C levels decreased, but vitamin E levels increased in the liver of CCl₄-treated rats. Hepatic superoxide dismutase (SOD) activities remained unchanged, but glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities decreased following CCl₄ treatment. In rats pretreated with artichoke extract, significant decreases in plasma transaminase activities and amelioration in histopathological changes in the liver were observed following CCl₄ treatment as compared to CCl₄-treated rats. In addition, hepatic MDA and DC levels decreased, but GSH levels and GSH-Px activities increased without any change in other antioxidant parameters following CCl₄ treatment in artichoke-pretreated rats. The present findings indicate that in vivo architoke extract administration may be useful for the prevention of oxidative stress-induced hepatotoxicity.

Introduction

Artichoke (Cynara scolymus L.) is a plant that is widely grown in Mediterranean countries and is rich in natural antioxidants. It contains caffeoylquinic acid derivatives (cynarin and chlorogenic acid) and flavonoids (luteolin, apigenin) (Llorach et al., 2002; Wang et al., 2003; Joy and Haber, 2007). The artichoke leaf extract has been used for hepatoprotective (Gebhardt, 1997; Aktay et al., 2000; Speroni et al., 2003), antimicrobial (Zhu et al., 2004) and cholesterol reducing (Pittler et al., 2002; Lupattelli et al., 2004) purposes. In vitro (Gebhardt, 1997; Brown and Rice-Evans, 1998; Perez-Garcia et al., 2000; Llorach et al., 2002; Zapolska-Downar et al., 2002; Jimenez-Escrig et al., 2003; Wang et al., 2003) and in vivo studies (Aktay et al., 2000; Jimenez-Escrig et al., 2003; Speroni et al., 2003) have shown that artichoke extract is very effective as an antioxidant and its health-protective potential has been attributed to its antioxidant power. It has been found to decrease the production of reactive oxygen species (Perez-Garcia et al., 2000; Zapolska-Downar et al., 2002), the oxidation of low-density lipoproteins (Brown and Rice-Evans, 1998; Zapolska-Downar et al., 2002; Jimenez-Escrig et al., 2003), lipid peroxidation (Gebhardt, 1997; Llorach et al., 2002; Speroni et al., 2003), protein oxidation (Jimenez-Escrig et al., 2003) and increase the activity of glutathione peroxidase (Jimenez-Escrig et al., 2003). Although it has been reported that artichoke may have protective effects against liver injury (Gebhardt, 1997; Aktay et al., 2000; Speroni et al., 2003), the experimental studies are insufficient.

Carbon tetrachloride (CCl₄) is a widely used agent to induce experimentally induced liver injury. While acute CCl₄ application results in hepatitis, chronic CCl₄ application has been shown to cause liver cirrhosis (Slater, 1982; Weber et al., 2003; Natarajan et al., 2006). Oxidative stress has been reported to play an important role in the pathogenesis of liver injury due to CCl₄ application (Slater, 1982; Weber et al., 2003; Natarajan et al., 2006).

In our study, we wanted to investigate whether artichoke leaf extract has a protective effect against CCl₄-induced oxidative stress and hepatotoxicity in rats.