ORIGINAL RESEARCH

Effects of empagliflozin and L-ornithine L-aspartate on behavior, cognitive functions, and physical performance in mice with experimentally induced steatohepatitis

Prikhodko VA1, Sysoev YuI1,2, Poveryaeva MA1, Bunyat AV1, Karev VE3, Ivkin DYu1, Sukhanov DS1, Shustov EB1, Okovityi SV1
About authors

1 Saint Petersburg State Chemical and Pharmaceutical University, Saint Petersburg, Russia

2 Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia

3 Pediatric Research and Clinical Center for Infectious Diseases of FMBA, Saint Petersburg, Russia

Correspondence should be addressed: Veronika A. Prikhodko
Krasnoputilovskaya, 76, k. 2, lit. А, Saint Petersburg, 196247; moc.hcetonnimrahp@okdohirp.akinorev

About paper

Funding: this work was part of the Saint-Petersburg State University project No. 51134206.

Compliance with ethical standards: the experiments were conducted in compliance with the Basel Declaration, the Order № 199 on the Principles of Good Laboratory Practice of the Ministry of Healthcare of the Russian Federation dated April 01, 2016, and the recommendations of the Bioethics Committee of Saint Petersburg State Chemical and Pharmaceutical University. The animals were housed in a vivarium under standard controlled laboratory conditions.

Author contribution: Prikhodko VA analyzed the literature; conducted the experiments; participated in statistical analysis and interpretation of the obtained data; wrote the manuscript and prepared the figures. Sysoev YuI planned the study; analyzed the literature; conducted the experiments; participated in statistical analysis and data interpretation; wrote the manuscript and prepared the figures. Poveryaeva MA conducted the experiments; Bunyat AV planned the study; conducted the experiments; Karev VE analyzed and interpreted the obtained data; wrote the manuscript and prepared the figures; Ivkin DYu planned the study; analyzed the literature; Sukhanov DS planned the study; analyzed and interpreted the obtained data; wrote the manuscript; Shustov EB, Okovityi SV planned the study; analyzed the literature; analyzed and interpreted the obtained data; wrote the manuscript.

Received: 2020-05-22 Accepted: 2020-06-08 Published online: 2020-06-21
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Non-alcoholic fatty liver disease (NAFLD) is a chronic condition characterized by disturbed carbohydrate and lipid metabolism and often complicated by psychoneurological symptoms, including anxiety, depression, memory deficit, and asthenia. Most studies of pharmacotherapy candidates for NAFLD focus on the ability of the tested drugs to restore the biochemical functions and morphology of the liver while their potential effects on the co-existing conditions remain overlooked. The aim of this paper was to investigate the effects of empagliflozin and L-ornithine L-aspartate (OA) on behavior, memory, and physical performance in C57BL/6 mice with experimentally induced NAFLD (6 months of a Western diet + weekly carbon tetrachloride injections). The disease affected animal behavior (locomotion speed decreased by 38% and 35%, p < 0.01; rearing increased by 432% and 279%, p < 0.05 etc.), induced long-term memory deficit (latency to find the target box increased by 108% in the Barnes maze, the number of errors increased by 439%, p < 0.05), and compromised physical performance (swimming time in the forced swim test dropped by 50%, p < 0.05 etc.). When administered during the high-calorie diet period, both drugs reduced anxiety (empagliflozin: the number of grooming bouts rose by 160%, p < 0.05 and 2173%, p < 0.01; time spent in the light compartment in the light/dark box test increased by 275%, p < 0.05, etc.; OA: time spent in the open arms of the maze increased by 267%, p < 0.05), and promoted memory retention in mice with NAFLD. OA improved physical performance (swimming time in the forced swimming test improved by 106%, p < 0.05, etc.). Thus, empagliflozin and OA can have a beneficial effect on cognitive functions, as well as behavior, and ameliorate asthenia in NAFLD.

Keywords: physical performance, non-alcoholic fatty liver disease, steatohepatitis, cognitive disorders, empagliflozin, L-ornithine L-aspartate

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