Combined saline and vildagliptin induced M2 macrophage polarization in hepatic injury induced by acute kidney injury

Shaimaa N Amin; Hader I Sakr; Walaa B El Gazzar; Sherif A Shaltout; Hazem S Ghaith; Dalia A Elberry

doi:10.7717/peerj.14724

Combined saline and vildagliptin induced M2 macrophage polarization in hepatic injury induced by acute kidney injury

PeerJ. 2023 Feb 13:11:e14724. doi: 10.7717/peerj.14724. eCollection 2023.

Authors

Shaimaa N Amin^{1

2}, Hader I Sakr^{2

3}, Walaa B El Gazzar^{1

4}, Sherif A Shaltout^{5

6}, Hazem S Ghaith⁷, Dalia A Elberry²

Affiliations

¹ Department of Anatomy, Physiology, and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan.
² Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
³ Department of Medical Physiology, Medicine Program, Batterjee Medical College, Jeddah, Saudi Arabia.
⁴ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Benha, Egypt.
⁵ Department of Pharmacology, Public health, and Clinical Skills, Faculty of Medicine, The Hashemite University, Zarqa, Jordan.
⁶ Department of Pharmacology, Faculty of Medicine, Benha University, Benha, Egypt.
⁷ Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

Abstract

Acute kidney injury (AKI) is a prevalent medical condition accompanied by mutual affection of other organs, including the liver resulting in complicated multiorgan malfunction. Macrophages play a vital role during tissue injury and healing; they are categorized into "classically activated macrophages" (M1) and "alternatively activated macrophages" (M2). The present study investigated and compared the conventional fluid therapy vs Dipeptidyl peptidase 4 inhibitor (DPP-4i) vildagliptin on the liver injury induced by AKI and evaluated the possible molecular mechanisms. Thirty rats comprised five groups (n = 6 rats/group): control, AKI, AKI+saline (received 1.5 mL of normal saline subcutaneous injection), AKI+vildagliptin (treated with oral vildagliptin 10 mg/kg), AKI+saline+vildagliptin. AKI was induced by intramuscular (i.m) injection of 50% glycerol (5 ml/kg). At the end of the work, we collected serum and liver samples for measurements of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrotic factor-α (TNF-α), and interleukin-10 (IL-10). Liver samples were processed for assessment of inducible nitric oxide synthase (iNOS) as a marker for M1, arginase 1 (Arg-1) as an M2 marker, c-fos, c-Jun, mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and high-mobility-group-box1 (HMGB1) protein. The difference was insignificant regarding the relative expression of AP-1, c-Jun, c-fos, MAPK, and HMGB between the AKI+saline group and the AKI+Vildagliptin group. The difference between the same two groups concerning the hepatic content of the M1 marker (iNOS) and the M2 marker Arg-1 was insignificant. However, combined therapy produced more pronounced changes in these markers, as the difference in their relative expression between the AKI+saline+Vildagliptin group and both the AKI+saline group and the AKI+Vildagliptin group was significant. Accordingly, we suggest that the combined saline and vildagliptin hepatoprotective effect involves the downregulation of the MAPK/AP-1 signaling pathway.

Keywords: Acute kidney injury; Dipeptidyl peptidase 4 inhibitor; Liver; MAPK/AP-1; Vildagliptin.

MeSH terms

Acute Kidney Injury* / etiology
Animals
Liver / metabolism
Macrophages / metabolism
Rats
Saline Solution
Transcription Factor AP-1*
Vildagliptin

Substances

Vildagliptin
Transcription Factor AP-1
Saline Solution

Associated data

figshare/10.6084/m9.figshare.17680328.v1

Grants and funding

The authors received no funding for this work.