ИСТИНА

Methanol is toxic to mammals due to detoxifying enzymes activity, especially alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH) oxidizing methanol to harmful formaldehyde and formic acid1. Previously we have shown that gut flora produces methanol, which in turn influences mammalian gene expression2,3. Particularly, methanol regulates expression of the genes that control the concentration of the formaldehyde in mammal tissues3. Failure of the methanol metabolism regulation could lead to formaldehyde accumulation and neuronal death, e.g., in patients with Alzheimer’s disease1. We suggest that activators of the ALDH2 enzymatic activity could decrease the concentration of formaldehyde in mammals. Alpha-lipoic acid (ALA) is a naturally produced antioxidant that was proven to increase ALDH2 enzymatic activity through an unknown mechanism. A qRT-PCR analysis revealed the increase of mRNA level of the detoxifying genes ALDH2, CAT and CYP2E1 in mice brain tissue after ALA administration. Moreover, ALA administration decreased the level of endogenous formaldehyde and methanol in plasma, as determined by gas chromatography and HPLC. These findings suggest that ALA could affect methanol and formaldehyde metabolism. ALA uptake leads to a decrease of volunteers' blood formaldehyde and acetaldehyde. Thus, ALA induces expression of detoxifying genes and diminishes aldehydes concentration. These observations could explain beneficial effects of ALA in clinical research studies of patients with Alzheimer’s disease. The study was supported by grant 16-34-00379 from RFBR. References: 1. Dorokhov et al., 2015. Physiol. Rev. 95(2), 603-644. 2. Dorokhov et al., 2012. PLoS One 7(4):e36122. 3. Shindyapina et al., 2014. PLoS One 9(7): e102837.