ANALYSIS OF THE STUDY OF 2% LIDOCAINE HYDROCHLORIDE SOLUTION HEPATOTOXICITY AT VARIOUS NUMBER OF INJECTIONS IN THE EXPERIMENT

Pohodenko-Chudakova I. O., Maksimovich E. V., Kuznetsov Y. O.

DENTISTRY

Scentific article

Abstract. The aim of the study was to analyze the differences in morphological preparations of liver tissue with different numbers of injections of 2% lidocaine hydrochloride solution into the head and neck region of experimental animals. Objects and methods. Experimental studies were carried out on 10 male laboratory white mice, which were injected with a 2% solution of lidocaine hydrochloride according to the technique developed by us into the submandibular region (a variant of mandibular anesthesia with an extraoral access) every 3-4 days (1, 3, 7, 11, 15 days, total 5 injection) in average therapeutic doses, based on the data of clinical pharmacology. Liver tissue was taken from the objects withdrawn from the experiment for pathohistological examination. Results. In the study of liver preparations, after the first injection of 2% lidocaine hydrochloride, multiple foci of necrosis of hepatocytes with or without perifocal inflammatory reaction, different in shape and size, were revealed. After second injection of local anesthetic, moderate parenchymal and interstitial edema, small foci of necrosis of hepatocytes, mainly centrilobular and near the central veins, with a perifocal cellular inflammatory reaction were observed morphologically. In single portal tracts, an inflammatory reaction and mild cholestasis are noted. After third injections of local anesthetic morphologically, the liver we revealed: plethora, foci of necrosis of hepatocytes with a perifocal inflammatory reaction, focal inflammatory infiltration of many portal tracts, moderate nuclear polymorphism, fatty degeneration of hepatocytes. After fourth injections of a 2% solution of lidocaine hydrochloride in liver preparations, we revealed plethora, small and large foci of necrosis of hepatocytes with a perifocal inflammatory reaction, focal inflammatory infiltration of the portal tracts, moderate nuclear polymorphism, fatty degeneration of hepatocytes. After fifth injections of local anesthetic in the liver, nuclear polymorphism was noted, multiple, mainly large, foci of necrosis of hepatocytes with a perifocal inflammatory reaction, inflammatory infiltration of the portal tracts, intraductal, cholestasis, inflammatory infiltration around the central veins, eosinophilic intranuclear inclusions were detected in some nuclei hepatocytes. Conclusion. As a result of the study, it was revealed that even after the firstinjection of a 2% solution of lidocaine hydrochloride, hepatotoxicity was detected, and it increases with the number of injections of this local anesthetic in the head and neck region.

hepatotoxicity, 2% lidocaine hydrochloride solution, experimental studies.

1. Alekseev VA, Afonin MV, Shabanov EV, Chuchunov AA. Opyt primenenija anketirovanija dlja vyjavlenija soputstvujushhej somaticheskoj patologii v praktike vracha stomatologa punkta neotlozhnoj stomatologicheskoj pomoshhi. Siber. J. of Life Sci. and Agriculture. 2017;9(2):41- 53. doi: 10.12731/wsd-017-2-41-53. [in Russian].
2. Belousov JuB, Kukes VG, Lepahin VK, Petrov VI. Klinicheskaja farmakologija : nacional’noe rukovodstvo. Moscow: GEOTOR-Media. 2009. 976 s. [in Russian].
3. Maksimovich EV, Pohodenko-Chudakova IO. Patologija gepatobilliarnoj sistemy u stomatologicheskih pacientov, kak faktor riska razvitija obshhih oslozhnenij. Medical J. 2012;40(2):81-3. [in Russian].
4. Pohodenko-Chudakova IO, Maksimovich EV, Kuralenya SF, Pishchik VA. Analiz morfologicheskih izmenenij pecheni i biohimicheskih pokazatelej syvorotki krovi pri chastyh povtornyh vvedenijah mestnyh anestetikov v jeksperimente. Med. Newsletter of Vyatka. 2015;3:28-30. [in Russian].
5. Bueverov AO. Lekarstvennye porazhenija pecheni. Russkiy meditsinskiy zhurnal. 2012;3:107-11. [in Russian].
6. European Association for the Study of the Liver. EASL clinical practice guidelines: drug-induced liver injury. J. Hepatol. 2019;70(6):1222- 31. doi: 10.1016/j.jhep.2019.02.014.
7. Lisi DM. Drug-induced liver injury: an overview. New Jersey US Pharm. 2016;41(12):30-4.
8. Chen M, Suzuki A, Borlak J, Andrade RJ, Lucena MI. Drug-induced liver injury: interactions between drug properties and host factors. J. Hepatol. 2015;63:503-14. doi: 10.1016/j.jhep.2015.04.016.
9.  Andrade R, Medina-Caliz I, Gonzalez-Jimenez A, Garcia-Cortes M, Lucena MI. Hepatic damage by natural remedies. Semin Liver Dis. 2018;38:21-40. doi: 10.1055/s-0038-1623518.
10. Hunt CM, Yuen NA, Stirnadel-Farrant HA, Suzuki A. Age-related differences in reporting of drug-associated liver injury: data-mining of WHO safety report database. Regul. Toxicol. Pharmacol. 2014;70:519-26. doi: 10.1016/j.yrtph.2014.09.007.
11. Yuan L, Kaplowitz N. Mechanisms of drug-induced liver injury. Clin. Liver Dis. 2013;17:507-18. doi: 10.1016/j.cld.2013.07.002.
12. Iorga A, Dara L, Kaplowitz N. Drug-induced liver injury: cascade of events leading to cell death, apoptosis or necrosis. Int. J. Mol. Sci. 2017;18:1018. doi: 10.3390/ijms18051018.
13. Will Y, Chen M. Drug-induced liver toxicity. methods in pharmacology and toxicology. Humana Press. 2018:3:3-18.
14. Fontana RJ, Hayashi PH, Barnhart H, Kleiner DE, Reddy KR, Chalasani N, et al. Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury. Am. J. Gastroenterol. 2015;110:1450-9. doi: 10.1038/ ajg.2015.283.
15. Pohodenko-Chudakova IO, Maksimovich EV. Vyjavlenie grupp riska razvitija obshhih reakcij na mestnye anestetiki u pacientov na ambulatornom stomatologicheskom prieme. Stomatologicheskiy zhurnal. 2014;122(2):88-91. [in Russian].

«Bulletin of problems biology and medicine» Issue 2 (160), 2021 year, 320-323 pages, index UDK 616.314-089.5:616-092.4

10.29254/2077-4214-2021-2-160-320-323