Non-alcoholic fatty liver disease and its complications are frequent causes of liver-related morbidity and mortality. Incretin glucagon-like peptide-1 (GLP-1) affects liver functions and metabolism. Although GLP-1 analogues are widely used in clinical practice, information regarding their potential toxic effect on hepatocytes in vitro is missing. Therefore, we evaluated the effect of GLP-1 analogue liraglutide on activity of caspases 3/7, cell viability and oxidative stress in primary cultures of hepatocytes. Primary cultures isolated from male Wistar rats fed a standard (ST1-group, 10% energy from fat) or a high-fat diet (HF-group, 71% fat) for 10 weeks were incubated with liraglutide (0.1-1000 nmol/l) for 24 h. Activities of caspases 3/7 and cellular dehydrogenases (WST-1), lactate dehydrogenase (LDH) leakage and oxidative stress (malondialdehyde concentration and DCFDA assay) were evaluated. HF-groups vs. ST1-groups showed higher caspases activity, LDH leakage and MDA production (p < 0.001) and lower cellular dehydrogenases activity (p < 0.01). Liraglutide induced a dose-dependent decrease of caspases activity in both groups, reduction of oxidative stress in HF-animals and exerted no negative effects on other parameters. In conclusion, GLP-1 analogue liraglutide decreased activity of caspases 3/7, reduced ROS production and didn't exhibit negative effects on cell viability and oxidative stress in primary cultures of hepatocytes isolated from lean and steatotic livers.

Centre for Research on Diabetes Metabolism and Nutrition 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Physiology Faculty of Medicine in Hradec Králové Charles University Hradec Králové Czech Republic

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