1North-Western State Medical University named after I.I. Mechnikov
2State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation
Brief summary
The features of sublethal (½ LD16) and lethal (1 LD50) rat poisoning with methanol were studied during the course (3 dose-escalation regimens) of the reversible alcohol dehydrogenase (ADH) inhibitor fomepizole (4-methylpyrazole). In these groups, a significant increase in formaldehyde concentration was noted in the first 6 hours after intragastric administration of methyl alcohol - 15- and 55-fold, respectively. Animal lethality within 2-6 days is associated with a significant increase of formic acid concentration in the plasma by 5-11 times, compared to intact animals. During methanol intoxication, fomepizole, used in various dosing regimens, did not affect the level of formaldehyde, but significantly reduced the formic acid concentration by 1.5 and 2 times 2 days after methanol poisoning in sublethal and lethal doses. Fomepizole provided a partial recovery of the blood plasma total antioxidant status (AOA), according to the ability to bind a stable radical diphenylpicrylhydrazyl (DPPH) and to the inhibition of 2-thiobarbituric acid (2-TBA) oxidation.
1. Criner G.J., Barnette R.E., D?Alonzo G. E. Critical Care Study Guide: Text and review. 2nd ed., New York, Springer, 2010. 1829 p. doi:10.1007/978-0-387-77452-7.
2. Rietjens, S.J. Ethylene glycol or methanol intoxication: which antidote should be used, fomepizole or ethanol / S.J. Rietjens, D.W. de Lange, J. Meulenbelt // Neth.J.Med. - 2014. -Vol. 72, 2. - P. 73‐79.
3. Malutina, N.N. Patofiziologicheskie i klinicheskie aspekti vozdeistviya metanola i formaldegida na organizm cheloveka / N.N. Malutina, L.A. Taranenko // Sovremennie problemi nayki i obrazovaniya. - 2014. - 2. - C. 1-11.
4. Shafi, H. Eight fatalies due to drinking methanol-tainted alcohol in Pakistan: A case report / H. Shafi, M. Imran, H. F. Usman and et.al. / Egyptian journal of forensic sciences. - 2016. - Vol. 6, 4. - P. 515-519. doi.org/10.1016/j.ejfs.2016.06.004.
5. http://www.interfax.ru/Russia/797087.
6. Panaloza, C.G. Hight sensitivity of femail cell to ethanol: methylation of DNA lowers Cyp2e1, generation more ROS / C.G. Panaloza, M. Cruz, G. Germain and et.al. // Cell Commun Signal. - 2020. - Vol.18, 1. - P. 111. doi: 10.1186/s12964-0220-00616-8.
7. El-Mas, M.M. Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons accounts for the pressor effect of ethanol in spontaneously hypertensive rats / M.M. El Mas, A.A. Abdel-Rahman / Am.J.Physiol.Heart.Circ.Physiol. - 2012. - Vol.302, 3. - P. H837-44. doi: 10.1152/ajpheart.00958.2011.
8. Jiang, Y. Alcohol metabolizing enzymes, microsomal ethanol oxidizing system, cytochrome P450 2E1, catalase, and aldehyde dehydrogenase in alcohol-associated liver disease / Y. Jiang, T. Zhang, P. Kusumanchi and et.al. // Biomedicines. - 2020. - Vol.8, 3. - P. 50. doi:10.3390/biomedicines8030050.
9. Manni, M.A. Monoamine oxidase is overactivated in left and right ventricles from ischemic hearts: an intriguing therapeutic target / M.A. Manni, S. Rigacci, V. Borchi and et.al. // Oxidative Medicine and cellular longevity. - 2016. - Vol. 2016. - 10 p. doi.org/10.1155/2016/4375418.
10. Ransy, C. Use of H2O2 to cause oxidative stress, the catalase issue / C. Ransy, C. Vaz, F. Bouillaud // Int.J.mol.Sci. - 2020. - Vol. 21, 23. - P. 9149. doi: 10.3390/ijms21239149.
11. Yu, H.J. Apoptosis induced by methanolextract of potentilla discolor in human mucoepidermoid carcinoma cells through STAT3/PuMA signaling axis / H.J. Yu, I.H. Ahn, I.H. Yang and et.al. // Mol.Med.Rep. - 2018. Vol.17, 5. - P. 5258-5264. doi:10.3892/mmr.2018.8468.
12. Nyjnii, V.P. Vliyanie komponentov sivyshnogo masla na efiraldegidnoi frakcii na ostryu toksichnost i narkoticheskoe deistvie etilovogo spirta / V.P. Nyjnii, I.V. Demeshina, I.G. Zabirova i dr. // Toksikol. vestnik. - 1999. - 2. - S. 2-8.
13. Arytunyan A.V. Metodi ocenki svobodno-radikalnogo okisleniya i antioksidantnoi sistemi organizma / A.V. Arytunyan, E.E. Dybrovina, N.N. Zibina. - Metodicheskie rekomendacii pod red. chl.-korr. RAMN V.H. Havinsona.
14. Pressman, P. A review of methanol poisoning: a crisis beyond ocular toxicology / P. Pressman, R. Clemens, S. Sahu and et.al.] // Cutaneous and ocular toxicology. - 2020. - P. 173-179.
15. Kyrashvili, L.V. Lipidnii metabolizm pri neotlojnih sostoyaniyah / L.V. Kyrashvili, V.G. Vasilkov. Penza. - 2003. - S. 145.
16. Alkogolizm i narkomaniya v regionah Rossiiskoi Federacii: ocenka masshtaba problemi na osnove dostypnih statisticheskih dannih. Informacionnaya platforma «Esli bit tochnim», 2021. - 61 s.
17. Drick, N. Fomepizole, ethanol or dialysis in the case of life-threatening ethylenglycol intoxication? / N. Drick, J.J. Schmidt, O.Wiesner and et.al. // Med Klin Intensivmed Notfmed. - 2021. - Vol. 116, 8. P. 698-701. doi: 10.1007/s00063-020-00718-8.
18. Rasamison, R. Analysis of fomepizole safety based on a 16-year post-marketing experience in France / R. Rasamison, H. Besson, M-P. Berleur and et.al. // Clin Toxicol (Phila). - 2020. - Vol. 58, 7. P. 742-747. doi: 10.1080/15563650.2019.1676899.
19. Yue, R. Activation of PPARα-catalase pathway reverses alcogolic liver injury via upregulating NAD synthesis and accelerating alcohol clearance / R. Yue, G-y Chen, G. Xie and et.al. // Free radical biology and medicine. - 2021. - Vol.174. - P. 249-263.