As far as some reactive species (free radicals) are messengers in electron transfer processes in the body, is it possible to increase the tolerance to alcohol by administration of antioxidant?
Well, my answer is "yes". I observed this in a very specific case - rat model of simultaneous diurnal rhythm disturbance due to 24 hrs light exposure and prolonged voluntary ethanol intake. I feel that, if there is a reactive specimen/species that work as a "stop" signal for further ethanol consumption, and if an antioxidant removes this reactive specimen/species, this antioxidant will enhance the tolerance to ethanol.
The problem is that in humans the antioxidants would seldom reach the necessary concentrations if naturally ingested with foods or beverages, e.g. resveratrol in wine (https://www.researchgate.net/publication/240306569_Can_resveratrol_in_wine_protect_against_the_carcinogenicity_of_ethanol_A_probabilistic_dose-response_assessment?ev=srch_pub).
Therefore you would need to supplement the antioxidants, which is often problematic due to the adverse effects of the substances if administered at the high dose levels used in the animal experiments (if possible at all due to regulatory restrictions).
Finally, even if antioxidants might ameliorate alcohol intolerance, there is a lack of evidence that this would exclude all detrimental effects of ethanol. Ethanol would likely to be longer in circulation at higher concentrations, than if it would be more rapidly oxidized?
Article Can resveratrol in wine protect against the carcinogenicity ...
Well, this is what I may share: Using rat models of prolonged voluntary ethanol intake we found that the treatment with water soluble vitamin E resulted in both diminished oxidative stress (OS) in tissues (different brain structures, total brain homogenate, liver homogenate, blood plasma) and in a decrease of the voluntary ethanol intake. Then we investigated the same parameters in a group exposed to 24 hrs light treatment for the same time period. We found a decreased OS in the tidssues. But if we combined the two rats models, the treatment with Trolox resulted in a decreased OS level, along with increased voluntary ethanol intake. It seems that, if we apply the antioxidant to a group alcoholic rats, we achieve some intolerance to ethanol and a decreased OS level. But if our rats-alcoholics are exposed to a diurnal rhythm disturbance via constant light treatment, a tolerance to ethanol occurs, accompanied with decreased OS level.
Now,we know that the OS is universal signal to the body that it has to adapt to a new environment or to new living conditions. The antioxidants (AO) may decrease via different mechanisms the amount of reactive species (RS). In the case of rat model of alcoholism, it seems that the application of an antioxidant decreaese the tolerance (increases the intolerance) to ethanol. Why, in combination with constant light exposure, the same AO increases the tolerance (decreases the intolerance) to alcohol? This is what I am asking myself. Has someone observed alcoholics patients with insomnia, who, after receiving antioxidant therapy, increased the voluntary ethanol intake?
In a paper I recently reviewed curcumin also provided significant protection against ethanol adminstration in rats.
Has the curcumin decreased the voluntary ethanol intake in rat model of prolonged alcohol consumption? As far as the systemic alcohol intake increases the free radicals in the body and alters the antioxidant defeninse, the antioxidants will decrease the oxidative stress in the alcoholic (human or model animal).
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