Science and Technology Production
Medicina - Unraveling the mechanism of alcohol hangover: the role of acetaldehyde and the possible protective action of N-acetyl cysteine.
Congress
Date:
2025Publishing House and Editing Place:
Fundación Revista MedicinaISSN:
1669-9106Summary *
Ethanol induces mitochondrial dysfunction and oxidative stress in brain cortex. Alcohol hangover (AH) involves physical and mental symptoms when blood alcohol concentration (BAC) approaches zero. Acetaldehyde, the byproduct of ethanol metabolism, was postulated as a primary contributor to AH-induced mitochondrial dysfunction, particularly at brain cortex synapses. We aimed toevaluate the possible role of acetaldehyde in AH synaptic damage and the potential beneficial effect of N-acetylcysteine (NAC). Male Swiss mice were used in two different experimental approaches depending on the use of 4-methylpyrazole (4-MP, an ADH inhibitor) or NAC. Animals were divided into four groups: saline (control), 4-MP (10 mg/kg) or NAC (500 mg/kg), ethanol (3.8 g/kg, AH group), and 4-MP/ethanol or NAC/ ethanol. Animals were sacrificed after 6 hours (BAC=0),and brain cortex synaptosomes were isolated. Results showed that reducing acetaldehyde levels significantly restored mitochondrial respiration, ATP synthesis, and coupling efficiency compared to the AH group (p<0.05).Treatment with 4-MP fully prevented the reduction in enzymatic activity of mitochondrial complex I-III caused by AH, while the activity of complex IV only partially recovered, remaining 50% lower than in the control group (p<0.05). 4-MP fully restored ATP production and mitochondrial membrane potential, which were reduced by 41% and 48% in the AH group, respectively (p<0.05). However, 4-MP intervention did not affect nitric oxide metabolism, suggesting that residual ethanol plays a role after ADH inhibition. NAC treatment significantly prevented impairments in oxygen uptake, mitochondrial membrane potential, ATP production, and enzymatic activity of the mitochondrial respiratory complexes due to AH (p<0.05). These findings underscore acetaldehyde as a key factorin the development of AH and demonstrate NAC’s potential to counteract AH pathology representing a promising strategy for mitigating its harmful effects. Information provided by the agent in SIGEVAKey Words
N-ACETYLCYSTEINE4-METHYLPYRAZOLEMITOCHONDRIAL FUNCTIONALCOHOL HANGOVER