Elsevier

Life Sciences

Volume 162, 1 October 2016, Pages 21-24
Life Sciences

Protective effect of treatment with thiamine or benfotiamine on liver oxidative damage in rat model of acute ethanol intoxication

https://doi.org/10.1016/j.lfs.2016.08.017Get rights and content

Abstract

Aims

The aim of this study was to evaluate possible beneficial effects of treatment with thiamine or benfotiamine in an animal model of acute ethanol intoxication.

Main methods

Thirty male Wistar rats were separated at random into three groups of 10 animals each: Ethanol (E), Ethanol treated with thiamine (T) and Ethanol treated with benfotiamine (BE). Rats were gavaged with single dose of ethanol (5 g/kg, 40% v:v). After 30 min of ethanol gavage the animals were treated with thiamine or benfotiamine. Six hours after first gavage, the animals were euthanized and blood and liver samples were collected for ethanol and oxidative stress biomarkers quantification.

Key findings

Serum ethanol levels were higher in animals treated with thiamine or benfotiamine while hepatic alcohol levels were higher in animals of the group treated with benfotiamine comparing to controls or thiamine treated groups. The lipid peroxidation biomarkers were diminished for the groups treated with thiamine or benfotiamine comparing to E animals. Concerning protein oxidative damage parameters, they were enhanced for animals treated with benfotiamine in relation to other groups.

Significance

In conclusion, the treatment with thiamine or benfotiamine even 30 min after the massive dose of ethanol has proven to be beneficial against liver damage. Improved results were obtained with benfotiamine in relation to oxidative damage from aqueous compartments.

Introduction

Ethanol metabolism produces free radicals and reactive oxygen species with consequent consumption of antioxidants leading to an imbalance between oxidants/antioxidants, known as oxidative stress. Several research groups have focused on the study of liver diseases caused by alcohol, since this is the organ responsible for about 95% of its catabolism [1]. The hepatic metabolism of ethanol is carried via three enzymatic pathways: pathway of alcohol dehydrogenase, the microsomal ethanol oxidation system (CYP2E1), and catalase [2], [3]. While these metabolic pathways are well elucidated in the literature, little attention is given to the quantification of ethanol in liver although this can be an important finding to know the metabolizing status of alcohol in this organ.

During the transformation of ethanol to acetaldehyde via CYP2E1 there is an overproduction of free radicals and reactive oxygen species, mainly in the forms of superoxide anion (O2), hydrogen peroxide (H2O2) and hydroxyethyl radical (CH3CH(•)single bondOH) [4], [5], [6]. These molecules are highly reactive and, as acetaldehyde, attack macromolecules, causing impairment or loss of function and, ultimately, cell death [7].

The use of antioxidants may help balance the hepatic antioxidant system reducing the deleterious effects caused by oxidative stress [8].

Thiamine, the vitamin B1, is a water soluble vitamin that plays essential role on energetic metabolism from carbohydrates. Benfotiamine is a weak soluble in water pro-vitamin B1 substance that displays better absorption and bioavailability compared with common pharmaceutical form available, thiamine hydrochloride, when administered orally, even after massive ethanol administration [12]. Thiamine therapeutic replacement is postulated in patients with Wernicke encephalopathy, especially alcoholics, due to deficiency of this vitamin in this particular group, because of poor dietary habits and a reduced absorption due to changes in the gastrointestinal system [9], [10]. Hypothetically, thiamine supply could increase the metabolism of ethanol by restoring the microsomal ethanol oxidizing system (MEOS).

Studies from our group have previously demonstrated some beneficial effects on intravenous administration of thiamine in an animal model of acute ethanol intoxication and more recently the high bioavailability of benfotiamine in rats acutely alcoholized [11], [12]. In humans, benfotiamine has been tested as oral treatment of alcoholic polyneuropathy with great improvement of the symptoms [13].

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines binge drinking as a pattern of drinking that brings blood alcohol concentration (BAC) levels to 0.8 g/L, typically occurring after 4 drinks for women and 5 drinks for men in about 2 h [14], [15]. In experimental models this can be achieved by forced administration of a massive dose of ethanol by gavage since animals do not voluntarily consume alcohol at concentrations that produce intoxication [15]. It has been showed that, as the chronic models, the acute ethanol intoxication produces an increase in hepatic oxidative stress.

In the present study we evaluate the effects of the administration of benfotiamine or thiamine on the improvement of hepatic oxidative damage and ethanol influx in a model of acute ethanol intoxication

Section snippets

Animals and experimental protocol

Thirty male Wistar rats, weighing 270–333 g, were obtained from the Central Animal Facilities of the Ribeirão Preto Campus, University of São Paulo, and allowed to acclimate for 1 week in the animal facilities of the Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, under controlled conditions of a 12-h light: dark cycle and temperature of 24 ± 2 °C in individual cages with free access to food and water. The experimental protocol was approved by the

Results

In Table 1 we note that the groups receiving treatment with thiamine and benfotiamine had higher serum ethanol (P < 0.05) than group E + S. The same behavior was observed for liver ethanol concentrations, but with E + BE group reaching values significantly higher (P < 0.05) than the E + T group. When we analyze the percentage of hepatic ethanol relative to the initial dose, a significant difference (P < 0.05) among the three groups that received ethanol was found, with values of 1.3 ± 1.3%, 2.5 ± 0.9% and 3.6 ± 

Discussion

This study aimed to evaluate the benefits of treatment with thiamine or benfotiamine against damage caused by acute ethanol administration in rats, an experimental model that produces effects similar to those caused by the massive intake (“binge drinking”) of ethanol in humans.

Although there are no reports in the literature, liver ethanol values can be auxiliary in the elucidation of the deleterious effects of hepatic metabolism of the substance. Thus, treatment with thiamine and benfotiamine

Conclusion

The treatment with thiamine or benfotiamine even 30 min after the massive dose of ethanol has proven to be beneficial against liver damage. Better results were obtained with benfotiamine related to oxidative damage from aqueous compartments.

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