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: 2020-06-22
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Fig. 1. A. Description of the NAFLD model, animal groups and the experimental design. Abbreviations: q.d. — once a day, q.w.— once a week, po — orally, ip — intraperitoneally. B. Survival dynamics. C. Histopathological slides of the liver. 1. No structural abnormalities in liver tissue in the intact group; 2. Morphological features of NAFLD in the control group, including marked macrovesicular steatosis and marked ballooning degeneration of hepatocytes, focal parenchymal infiltration by polymorphonuclear leukocytes; 3. Morphological features of NAFLD in the EMPA group, including mild macrovesicular steatosis and mild ballooning degeneration of hepatocytes, no pathological infiltration of the liver parenchyma; 4. Moderate macrovesicular steatosis and moderate ballooning of hepatocytes, moderate parenchymal infiltration by polymorphonuclear cells in the OA group. A, B, C, D — hematoxylin-eosin staining, ×200
Fig. 2. Results of (A) the Open field test, (B) the Elevated plus maze test and (C) the Light/dark box test. * — p < 0.05; ** — p < 0.01
Fig. 3. Results of spatial memory assessment in the Barnes maze. Gray— Intact, green — Control, red — EMPA, yellow — OA; # — p < 0.05, day 12 vs day 5
Fig. 4. Results of the Forced swim test (A) and the Triple weight-loaded exhaustive swim test (B). Gray — Intact, green — Control, red — EMPA, yellow — OA; * — p < 0.05; ** — p < 0.01; # — p < 0.05; ## — p < 0.01, comparison with the initial result; $ — p < 0.05, $$ — p < 0.01, comparison with the second trial (5 min after the first trial)
Fig. 5. Graphic representation of principal component analysis results. Gray — Intact, green — Control, red — EMPA, yellow — OA