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Hepatoprotective effects of gemigliptin and empagliflozin in a murine model of diet-induced non-alcoholic fatty liver disease.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2022 Jan 15; Vol. 588, pp. 154-160. Date of Electronic Publication: 2021 Dec 20. - Publication Year :
- 2022
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Abstract
- Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of liver diseases characterized by steatosis, inflammation, and fibrosis. This study aimed to investigate the potential of dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors in alleviating the progression of NAFLD. The NAFLD model was generated by feeding male C57BL/6J mice a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 7 weeks. After 2 weeks of CDAHFD feeding, the NAFLD model mice were assigned to four groups, namely (ⅰ) VEHICLE, (ⅱ) gemigliptin (GEMI), (ⅲ) empagliflozin (EMPA), and (ⅳ) GEMI + EMPA. For the next 5 weeks, mice received the vehicle or the drug based upon the group to which they belonged. Thereafter, the triglyceride concentration, extent of fibrosis, and the expression of genes encoding inflammatory cytokines, chemokines, and antioxidant enzymes were analyzed in the livers of mice. The NAFLD activity score and hepatic fibrosis grade were assessed via hematoxylin and eosin and Sirius Red staining of the liver tissue samples. All mice belonging to the GEMI, EMPA, and GEMI + EMPA groups showed improvements in the accumulation of liver triglycerides and the expression of inflammatory cytokines and chemokines. Additionally, the oxidative stress was reduced due to inhibition of the c-Jun N-terminal kinase pathway and upregulation of the antioxidant enzymes. Furthermore, in these three groups, the galectin-3 and interleukin 33-induced activity of tumor necrosis factor-α was inhibited, thereby preventing the progression of liver fibrosis. These findings suggest that the GEMI, EMPA, and GEMI + EMPA treatments ameliorate hepatic steatosis, inflammation, oxidative stress, and fibrosis in CDAHFD-induced NAFLD mouse models.<br />Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Hae Jin Kim reports financial support was provided by National Research Foundation of Korea (NRF).<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acids
Animals
Benzhydryl Compounds pharmacology
Choline
Cytokines metabolism
Disease Models, Animal
Disease Progression
Glucosides pharmacology
Inflammation pathology
Inflammation Mediators metabolism
JNK Mitogen-Activated Protein Kinases metabolism
Liver drug effects
Macrophage Activation drug effects
Male
Mice, Inbred C57BL
Oxidative Stress drug effects
Phosphorylation drug effects
Protective Agents pharmacology
Mice
Benzhydryl Compounds therapeutic use
Diet, High-Fat
Glucosides therapeutic use
Liver pathology
Non-alcoholic Fatty Liver Disease drug therapy
Piperidones pharmacology
Piperidones therapeutic use
Protective Agents therapeutic use
Pyrimidines pharmacology
Pyrimidines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 588
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 34971904
- Full Text :
- https://doi.org/10.1016/j.bbrc.2021.12.065