Elsevier

Life Sciences

Volume 73, Issue 7, 4 July 2003, Pages 933-946
Life Sciences

Role of naringin supplement in regulation of lipid and ethanol metabolism in rats

https://doi.org/10.1016/S0024-3205(03)00358-8Get rights and content

Abstract

The current study was performed to investigate the effect of naringin supplements on the alcohol, lipid, and antioxidant metabolism in ethanol-treated rats. Male Sprague-Dawley rats were randomly divided into six groups (n = 10) based on six dietary categories: ethanol and naringin-free, ethanol (50 g/L) plus low-naringin (0.05 g/L), ethanol plus high-naringin (0.125 g/L), and three corresponding pair-fed groups. The pair-fed control rats received an isocaloric diet containing dextrin-maltose instead of ethanol for 5 wks. Among the ethanol treated groups, the naringin supplements significantly lowered the plasma ethanol concentration with a simultaneous increase in the ADH and/or ALDH activities. However, among the ethanol-treated groups, naringin supplementation resulted in a significant decrease in the hepatic triglycerides and plasma and hepatic total cholesterol compared to that in the naringin-free group. Naringin supplementation significantly increased the HDL-cholesterol and HDL-C/total-C ratio, while lowering the AI value among the ethanol-treated groups. Hepatic lipid accumulation was also significantly reduced in the naringin-supplemented groups compared to the naringin-free group among the ethanol-treated groups, while no differences were found among the pair-fed groups. Among the ethanol-treated groups, the low-naringin supplementation resulted in a significant decrease in the levels of plasma and hepatic TBARS, whereas it resulted in higher SOD and GSH-Px activities and gluthathion levels in the liver. Accordingly, naringin would appear to contribute to alleviating the adverse effect of ethanol ingestion by enhancing the ethanol and lipid metabolism as well as the hepatic antioxidant defense system.

Introduction

It is generally recognized that excess alcohol consumption is associated with a variety of adverse pathologic effects. As such, many animal trials have already been conducted in an attempt to reduce these pathological changes (Lieber et al., 1989). Alcohol consumption has been found to increase the formation of free radicals in rat livers (Knecht et al., 1995). Oxidative stress is the term used to describe an imbalance favoring pro-oxidants and/or disfavoring antioxidants, potentially leading to damage (Sies, 1985), and hepatic oxidative stress or the resulting lipid peroxidation has been identified as playing a pathogenic role in alcoholic liver disease (Daniel, 1999).

Many plant products, including certain fruits and vegetables, contain polyphenolic compounds that are potent antioxidants (Rice-Evans et al., 1995). For example, natural flavonoids are known for their significant scavenging of oxygen radicals in vivo and in vitro, thereby affecting various steps in the arachidonate cascade via cyclo-oxygenase or lipoxygenase Abad et al., 1995, Robak and Gryglewsky, 1996. Flavonoids are already widely recognized as naturally occurring antioxidants that inhibit lipid peroxidation in biological membranes (Maridonneau-Parini et al., 1986). The major structure of flavonoids producing these antioxidant effects is known to have at least one free aromatic hydroxyl group (Ng et al., 2000). Considerable interest has been shown in the role of the major phenolic phytochemical components in citrus fruits and other edible plants as dietary antioxidants (Jeon et al., 2001). Naringin, a citrus bioflavonoids, has been demonstrated as antioxidants, anti-cancer agents, and potent cholesterol-lowering agents in previous animal studies Haenen et al., 1997, Kroyer, 1986, Francis et al., 1989, Shin et al., 1999.

In general, ethanol has been shown to both generate ROS and attenuate antioxidant enzymes activities (Dinu and Zanfir, 1991). As a result, increased oxidative stress has been suggested as one of the mechanisms involved in the development of complications related to ethanol intoxication Dianzani, 1987, Strubelt et al., 1987. However, very little is known about the interaction between naringin and the metabolism of ethanol.

Accordingly, the current study evaluated the effect of naringin against liver damage in ethanol-administered rats based on analyzing alcohol-metabolizing enzymes, antioxidant enzymes, and hepatic lipid accumulation.

Section snippets

Animals and diets

Sixty male Sprague-Dawley rats weighing between 140 and 150 g were purchased from Bio Genomics Inc. (Seoul, Korea). The animals were all individually housed in stainless steel cages in an air-conditioned room with controlled temperature (20∼23 °C) and automatic lighting (alternating 12-h periods of light and dark) and fed a pelletized chow diet for 1 week after arrival. Next, the animals were randomly divided into six groups (n = 10) based on six dietary categories: naringin-free ethanol,

Effect on food intake, weight gain, and organ weights

There were no significant differences in the food intake, weight gain or organ weights among the ethanol or pair-fed groups (Table 2). However, the ethanol groups revealed a significantly lower weight gain yet higher organ weights compared to the corresponding pair-fed groups, except for the heart weight in the high-naringin group.

Effect on plasma ethanol concentration

The naringin supplements significantly lowered the ethanol concentration in the plasma when compared among the ethanol-treated groups (Fig. 1), yet the effect of

Discussion

Alcohol is initially oxidized into acetaldehyde, principally by ADH, and then into acetate by ALDH. Acetaldehyde, a highly toxic metabolite of ethanol, has already been implicated in the pathogenesis of alcoholic liver disease (Lieber, 1994). Theoretically, the accumulation of acetaldehyde in the liver after chronic alcohol ingestion is determined by its formation and removal rates as catalyzed by ADH and ALDH, respectively Lee et al., 2001a, Lee et al., 2001b.

In the current study, when the two

Acknowledgements

This work was supported by the Korea Research Foundation Grant (KRF-2000-D00315).

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