Published Article
Protective Effect Of Some Vitamins Against The Toxic Action Of Ethanol On Liver Regeneration Induced By Partial Hepatectomy In Rats.
World J Gastroenterol 2008 February 14; 14(6): 899-907 ISSN 1007-9327.
AIM: To investigate the effects of vitamins (A, C and E) on liver injury induced by ethanol administration during liver regeneration in rats.
METHODS: Male Wistar rats subjected to 70% partial hepatectomy were divided into five groups (groups 1-5). During the experiment, animals of Group 1 drank only water. The other four groups (2-5) drank 30 mL of ethanol/L of water. Group 3 additionally received vitamin A, those of group 4 vitamin C and those of group 5 received vitamin E. Subsequently serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin and bilirubin were measured colorimetrically. Lipid peroxidation (thiobarbituric-acid reactive substances, TBARS) both in plasma and liver was measured, as well as liver mass gain assessment and total DNA.
RESULTS: Compared with sham group, serum AST and ALT increased significantly under ethanol treatment (43% and 93%, respectively, with P < 0.05). Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity. Ethanol treatment also decreased serum albumin concentration compared to sham group (3.1 ± 0.4 g/dL vs 4.5 ± 0.2 g/dL; P < 0.05). During liver regeneration vitamins C and E significantly ameliorated liver injury for ethanol administration in hepatic lipid peroxidation (4.92 nmol/mg and 4.25 nmol/mg vs 14.78 nmol/mg, respectively, with P < 0.05). In association with hepatic injury, ethanol administration caused a significant increase in both hepatic and plasma lipid peroxidation. Vitamins (C and E) treatment attenuated hepatic and plasma lipid peroxidation.
CONCLUSION: Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus appear to be significantly more effective than vitamin A against ethanol-mediated toxic effects during liver regeneration.
INTRODUCTION
Alcohol liver disease is a world-wide medical complication of alcohol abuse[1]. Although important progress has been made in understanding its pathogenesis, the mechanisms involved in its development are as yet not fully understood.
Oxidative stress is a key step in the pathogenesis of ethanol-associated liver injury. The deleterious effects of alcohol, at least partly involve oxidative injury that has been documented by measurement of oxidant radicals, alterations in oxidant/antioxidant balance and oxidant induced changes in cellular proteins and lipids[2]. After ethanol is absorbed, it is distributed to all tissue, and body fluids in direct proportion to blood levels[3]. Ethanol affects the liver more than any other organ[4], since its metabolism implies generation of free radicals that can damage cell structure and function, particularly when antioxidant mechanisms are not able to neutralize them[5,6]. Animal models show the mechanisms by which both acute alcohol administration and chronic alcohol consumption affect the liver.
Chronic ethanol administration induces an increase in lipid peroxidation either by enhancing the production of oxygen reactive species, or by decreasing the level of endogenous antioxidants[7]. Short-term ethanol administration has been reported to decrease vitamins and increase superoxide generation in the liver[8]. The enhanced superoxide generation increases lipid peroxidation and induces liver dysfunction in rats that have been subjected to acute ethanol exposure.
One of the most prominent antioxidant defense systems are vitamins (A, C and E ) acting as co-factors for many enzymes, protecting cells against free radical-mediated damage[10], as free radical scavengers. Besides, large ethanol intakes have deleterious effects on nutritional status[7,8].
Recently, it has become clear that antioxidant nutrients, including vitamins, are important for neurological function[11-13]. High intake of vitamins E and C have been found to be associated with lower risk of Alzheimer's disease[14]. In addition, evidence for alcohol-induced oxidant injury comes from studies in which pretreatment with antioxidants such as vitamin E, vitamin C, and agents that enhance antioxidant capacity attenuate alcohol induced effects[15].
Nutrient intermediary metabolism is a vital function of the healthy adult liver. Fortunately, the liver appears to have a tremendous reserve capacity in this regard, since general nutritional status is well-preserved until severe hepatic parenchymal loss occurs. Indeed, several clinical and biochemical markers of nutritional status are often used to gauge the severity of liver dysfunction, with evidence of severe malnutrition implying end-stage liver disease. Hepatocyte proliferation occurs rarely in healthy adults, but it is necessary to replace liver cells lost by hepatic necrosis or resection. These facts have prompted speculation on whether decreased hepatic mass and metabolism are involved in the initiation and progression of hepatic regeneration following liver injury[16]. Restoration of normal hepatic structure and function is the goal of therapy for acute and chronic liver injury of varying etiologies. Consequently, strategies to optimize compensatory hepatic regenerative growth have tremendous therapeutic relevance. Better understanding of the mechanism regulating cellular proliferation, and organ regeneration will play a critical role in designing treatments to enhance liver regeneration[16]. Current knowledge suggests several approaches
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