scbmtБИОМЕДИЦИНАJournal Biomed2074-59822713-0428Scientific center of biomedical technologies of Federal Medical and Biological Agency10.33647/2074-5982-18-3-128-132scbmt-1413Research ArticleДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ В БИОМЕДИЦИНЕNON-CLINICAL RESEARCH IN BIOMEDICINEВлияние орнитина аспартата и эмпаглифлозина на проявления мнестического дефицита при экспериментальном стеатогепатитеEffects of Ornithine Aspartate and Empagliflozin on Memory Deficit Symptoms in Experimental SteatohepatitisПриходькоВ. А.PrikhodkoV. A.

Приходько Вероника Александровна.

197376, Санкт-Петербург, ул. Профессора Попова, 14, лит. А.

Veronika A. Prikhodko.

197376, St. Petersburg, Professora Popova Str., 14, lit. A.

veronika.prihodko@pharminnotech.comФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет»РоссияSt. Petersburg State Chemical and Pharmaceutical University of the Ministry of Health Care of RussiaRussian Federation202217102022183128132Copyright © Приходько В.А., 20222022Приходько В.А.Prikhodko V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.scbmt.ru/jour/article/view/1413

В настоящем исследовании проведена оценка влияния L-орнитина L-аспартата и эмпаглифлозина на состояние гиппокамп-зависимых видов памяти при неалкогольном стеатогепатите (НАСГ) у мышей линии C57Bl/6. Установлено, что НАСГ сопровождается транзиторным снижением краткосрочной распознающей памяти на ранних этапах, а также прогрессирующим ослаблением рабочей пространственной памяти. L-орнитина L-аспартат предупреждает развитие дефицита распознающей, но не пространственной памяти, в то время как эмпаглифлозин не оказывает заметного влияния на состояние мнестических функций животных.

In this study, L-ornithine L-aspartate and empagliflozin were evaluated in terms of their potential effects on the hippocampus-dependent memory status in non-alcoholic steatohepatitis (NASH) in C57Bl/6 mice. NASH was found to be associated with an early transient decrease in the short-term recognition memory as well as a progressive reduction in the short-term spatial memory. L-ornithine L aspartate effectively prevented the impairment of recognition, rather than spatial, memory. At the same time, empagliflozin failed to improve the memory status of the animals.

орнитина аспартатэмпаглифлозинрасстройства памятинеалкогольный стеатогепатитнеалкогольная жировая болезнь печениornithine aspartateempagliflozinmemory deficitnon-alcoholic steatohepatitisnon-alcoholic fatty liver diseaseReferencesBroadbent N.J., Squire L.R., Clark R.E. Spatial memory, recognition memory, and the hippocampus. Proc. Natl. Acad. Sci. U. S. A. 2004;101(40):14515-14520. DOI: 10.1073/pnas.0406344101.Broadbent N.J., Squire L.R., Clark R.E. Spatial memory, recognition memory, and the hippocampus. Proc. Natl. Acad. Sci. U. S. A. 2004;101(40):14515-14520. DOI: 10.1073/pnas.0406344101.Butterworth R.F. L-Ornithine L-Aspartate (LOLA) for the treatment of hepatic encephalopathy in cirrhosis: Novel insights and translation to the clinic. Drugs. 2019;79(Suppl 1):1-3. DOI: 10.1007/s40265-018-1021-4.Butterworth R.F. L-Ornithine L-Aspartate (LOLA) for the treatment of hepatic encephalopathy in cirrhosis: Novel insights and translation to the clinic. Drugs. 2019;79(Suppl 1):1-3. DOI: 10.1007/s40265-018-1021-4.Deacon R.M., Rawlins J.N. T-maze alternation in the rodent. Nat. Protoc. 2006;1(1):7-12. DOI: 10.1038/nprot.2006.2.Deacon R.M., Rawlins J.N. T-maze alternation in the rodent. Nat. Protoc. 2006;1(1):7-12. DOI: 10.1038/nprot.2006.2.George E.S., Sood S., Daly R.M., Tan S.Y. Is there an association between non-alcoholic fatty liver disease and cognitive function? A systematic review. BMC Geriatr. 2022;22(1):47. DOI: 10.1186/s12877-021-02721-w.George E.S., Sood S., Daly R.M., Tan S.Y. Is there an association between non-alcoholic fatty liver disease and cognitive function? A systematic review. BMC Geriatr. 2022;22(1):47. DOI: 10.1186/s12877-021-02721-w.Higarza S.G., Arboleya S., Gueimonde M., Gomez-Lazaro E., Arias J.L., Arias N. Neurobehavioral dysfunction in non-alcoholic steatohepatitis is associated with hyperammonemia, gut dysbiosis, and metabolic and functional brain regional deficits. PLoS One. 2019;14(9):e0223019. DOI: 10.1371/journal.pone.0223019.Higarza S.G., Arboleya S., Gueimonde M., Gomez-Lazaro E., Arias J.L., Arias N. Neurobehavioral dysfunction in non-alcoholic steatohepatitis is associated with hyperammonemia, gut dysbiosis, and metabolic and functional brain regional deficits. PLoS One. 2019;14(9):e0223019. DOI: 10.1371/journal.pone.0223019.Kjærgaard K., Mikkelsen A.C.D., Wernberg C.W., Grønkjær L.L., Eriksen PL., Damholdt M.F., Mookerjee R.P., Vilstrup H., Lauridsen M.M., Thomsen K.L. Cognitive dysfunction in non-alcoholic fatty liver disease-current knowledge, mechanisms and perspectives. J. Clin. Med. 2021;10(4):673. DOI: 10.3390/jcm10040673.Kjærgaard K., Mikkelsen A.C.D., Wernberg C.W., Grønkjær L.L., Eriksen PL., Damholdt M.F., Mookerjee R.P., Vilstrup H., Lauridsen M.M., Thomsen K.L. Cognitive dysfunction in non-alcoholic fatty liver disease-current knowledge, mechanisms and perspectives. J. Clin. Med. 2021;10(4):673. DOI: 10.3390/jcm10040673.Leger M., Quiedeville A., Bouet V., Haelewyn B., Boulouard M., Schumann-Bard P., Freret T. Object recognition test in mice. Nat. Protoc. 2013;8(12):2531-2537. DOI: 10.1038/nprot.2013.155.Leger M., Quiedeville A., Bouet V., Haelewyn B., Boulouard M., Schumann-Bard P., Freret T. Object recognition test in mice. Nat. Protoc. 2013;8(12):2531-2537. DOI: 10.1038/nprot.2013.155.Prikhodko V.A., Sysoev Yu.I., Poveryaeva M.A., Bunyat A.V., Ivkin D.Y., Sukhanov D.S., Shustov E.B., Okovityi S.V., Karev V.E. Effects of empagliflozin and L-ornithine L-aspartate on behavior, cognitive functions, and physical performance in mice with experimentally induced steatohepatitis. Bull. Russ. State Med. Univ. 2020;(3):49-57. DOI: 10.24075/brsmu.2020.034.Prikhodko V.A., Sysoev Yu.I., Poveryaeva M.A., Bunyat A.V., Ivkin D.Y., Sukhanov D.S., Shustov E.B., Okovityi S.V., Karev V.E. Effects of empagliflozin and L-ornithine L-aspartate on behavior, cognitive functions, and physical performance in mice with experimentally induced steatohepatitis. Bull. Russ. State Med. Univ. 2020;(3):49-57. DOI: 10.24075/brsmu.2020.034.Tsuchida T., Lee Y.A., Fujiwara N., Ybanez M., Allen B., Martins S., Fiel M.I., Goossens N., Chou H.I., Hoshida Y., Friedman S.L. A simple diet-and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver. J. Hepatol. 2018;69(2):385-395. DOI: 10.1016/j.jhep.2018.03.011.Tsuchida T., Lee Y.A., Fujiwara N., Ybanez M., Allen B., Martins S., Fiel M.I., Goossens N., Chou H.I., Hoshida Y., Friedman S.L. A simple diet-and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver. J. Hepatol. 2018;69(2):385-395. DOI: 10.1016/j.jhep.2018.03.011.

The authors declare that there are no conflicts of interest present.