Mechanisms of Ethanol Mixture Toxicity

Another mechanism of ethanol toxicity involves oxidative stress. Ethanol-induced liver disease is associated with significant oxidative stress as well as with increased levels of iron, which is also known to initiate oxidative stress in the liver. The combined oxidative stress induced by ethanol and iron greatly increases results in lipid peroxidation and the production of aldehydes such as 4-hydroxy-2-nonenal, compounds that have 

The following are examples of the effect of ethanol on nutritional components and drugs that are caused by metabolic induction. 

Retinol is metabolized by the same enzymes that oxidize ethanol. As a result, prolonged use of ethanol, which induces those degradative enzymes, results in the breakdown of retinol to toxic metabolites. Ethanol also interferes with the conversion of beta-carotene, a precursor to vitamin A, to retinol. Thus, ethanol both promotes a deficiency of vitamin A and enhances its toxicity and that of beta-carotene.  

Acetaminophen (APAP) is a widely used analgesic. Pretreatment with APAP followed by ethanol intake increases the metabolism of APAP and thereby its toxicity. Binge drinking of ethanol increases the hepatotoxicity of APAP. Caffeine also activates the metabolism of APAP and it, too, increases the hepatotoxicity of APAP. The combination of ethanol and caffeine significantly increases the liver toxicity of APAP.  

Caffeine causes intracellular calcium levels to increase and thereby increases apoptosis induction. Ethanol promotes higher calcium levels and higher apoptotic rates than caffeine. When caffeine and ethanol are combined, calcium levels and apoptosis are markedly elevated, indicating that the apoptotic effect of ethanol is potentiated when it is mixed with caffeine 

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