SGLT2 inhibitor empagliflozin monotherapy alleviates renal oxidative stress in albino Wistar diabetic rats after myocardial infarction induction
Acute kidney injury (AKI) is a sudden insult of the kidney that happens within a short period of time, which is associated with poor prognosis in diabetic patients with myocardial infarction (MI). Subclinical AKI is a condition in which tubular damage biomarkers [Neutrophil gelatinase-associated lip...
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doaj-b5c1679ef4e643efb1737a4d416d51be2021-06-03T04:55:09ZengElsevierBiomedicine & Pharmacotherapy0753-33222021-07-01139111624SGLT2 inhibitor empagliflozin monotherapy alleviates renal oxidative stress in albino Wistar diabetic rats after myocardial infarction inductionAhmed S. Ahmed0Marwa M. Mona1Mona A. Abdel‑Kareem2Rasha A. Elsisy3Anatomy and Embryology Department, College of Medicine, Tanta University, Tanta 31511, Egypt; Correspondence to: College of Medicine, Anatomy Department, Tanta University, Gharbia, Tanta, Egypt.Medical Biochemistry and Molecular Biology Department, College of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, EgyptAnatomy and Embryology Department, College of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, EgyptAnatomy and Embryology Department, College of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, EgyptAcute kidney injury (AKI) is a sudden insult of the kidney that happens within a short period of time, which is associated with poor prognosis in diabetic patients with myocardial infarction (MI). Subclinical AKI is a condition in which tubular damage biomarkers [Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1(KIM-1)] are positive even in the absence of elevated serum creatinine. Recent studies reported that SGLT-2 inhibitors could protect against subclinical AKI in diabetic patients by elevating the level of β-Hydroxybutyric acid (βOHB). This study aims to examine the reno-protective potential of empagliflozin (EMPA) against MI associated AKI in diabetic rats. Eighty Albino Wistar rats were divided into: (1) nondiabetic sham group (CS), (2) nondiabetic + myocardial infarction group (CM), (3) diabetic + myocardial infarction group (DM) and (4) diabetic + myocardial infarction + empagliflozin group (DME). At the end of the experiment, blood samples and kidneys were collected for biochemical analysis, histopathological, and immunohistochemical studies. After induction of myocardial infarction, there was a significant decrease in serum creatinine and NGAL levels in DME. After EMPA administration, mesangial matrix index and glomerular area were lowered in DME if compared to DM group. As a marker for tubular injury, we used anti-NGAL and anti-KIM-1 immunohistochemistry. Strong positive reaction was noticed in DM group if compared to DME group which showed weak positive reaction. Levels of renal mRNAs [NGAL; KIM-1; Nox-2,4; TLR-2,4; MyD88; TNF- α and IL-1 β, 18] in DME group were reduced significantly compared to DM group. In conclusion, empagliflozin can protect against subclinical acute kidney injury in diabetic albino Wistar rats after myocardial infarction induction, which could improve the clinical outcome of SGLT-2 inhibitors in diabetic patients.http://www.sciencedirect.com/science/article/pii/S0753332221004091SGLT2 inhibitorEmpagliflozinRenalMyocardial infarctionAKI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ahmed S. Ahmed Marwa M. Mona Mona A. Abdel‑Kareem Rasha A. Elsisy |
spellingShingle |
Ahmed S. Ahmed Marwa M. Mona Mona A. Abdel‑Kareem Rasha A. Elsisy SGLT2 inhibitor empagliflozin monotherapy alleviates renal oxidative stress in albino Wistar diabetic rats after myocardial infarction induction Biomedicine & Pharmacotherapy SGLT2 inhibitor Empagliflozin Renal Myocardial infarction AKI |
author_facet |
Ahmed S. Ahmed Marwa M. Mona Mona A. Abdel‑Kareem Rasha A. Elsisy |
author_sort |
Ahmed S. Ahmed |
title |
SGLT2 inhibitor empagliflozin monotherapy alleviates renal oxidative stress in albino Wistar diabetic rats after myocardial infarction induction |
title_short |
SGLT2 inhibitor empagliflozin monotherapy alleviates renal oxidative stress in albino Wistar diabetic rats after myocardial infarction induction |
title_full |
SGLT2 inhibitor empagliflozin monotherapy alleviates renal oxidative stress in albino Wistar diabetic rats after myocardial infarction induction |
title_fullStr |
SGLT2 inhibitor empagliflozin monotherapy alleviates renal oxidative stress in albino Wistar diabetic rats after myocardial infarction induction |
title_full_unstemmed |
SGLT2 inhibitor empagliflozin monotherapy alleviates renal oxidative stress in albino Wistar diabetic rats after myocardial infarction induction |
title_sort |
sglt2 inhibitor empagliflozin monotherapy alleviates renal oxidative stress in albino wistar diabetic rats after myocardial infarction induction |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2021-07-01 |
description |
Acute kidney injury (AKI) is a sudden insult of the kidney that happens within a short period of time, which is associated with poor prognosis in diabetic patients with myocardial infarction (MI). Subclinical AKI is a condition in which tubular damage biomarkers [Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1(KIM-1)] are positive even in the absence of elevated serum creatinine. Recent studies reported that SGLT-2 inhibitors could protect against subclinical AKI in diabetic patients by elevating the level of β-Hydroxybutyric acid (βOHB). This study aims to examine the reno-protective potential of empagliflozin (EMPA) against MI associated AKI in diabetic rats. Eighty Albino Wistar rats were divided into: (1) nondiabetic sham group (CS), (2) nondiabetic + myocardial infarction group (CM), (3) diabetic + myocardial infarction group (DM) and (4) diabetic + myocardial infarction + empagliflozin group (DME). At the end of the experiment, blood samples and kidneys were collected for biochemical analysis, histopathological, and immunohistochemical studies. After induction of myocardial infarction, there was a significant decrease in serum creatinine and NGAL levels in DME. After EMPA administration, mesangial matrix index and glomerular area were lowered in DME if compared to DM group. As a marker for tubular injury, we used anti-NGAL and anti-KIM-1 immunohistochemistry. Strong positive reaction was noticed in DM group if compared to DME group which showed weak positive reaction. Levels of renal mRNAs [NGAL; KIM-1; Nox-2,4; TLR-2,4; MyD88; TNF- α and IL-1 β, 18] in DME group were reduced significantly compared to DM group. In conclusion, empagliflozin can protect against subclinical acute kidney injury in diabetic albino Wistar rats after myocardial infarction induction, which could improve the clinical outcome of SGLT-2 inhibitors in diabetic patients. |
topic |
SGLT2 inhibitor Empagliflozin Renal Myocardial infarction AKI |
url |
http://www.sciencedirect.com/science/article/pii/S0753332221004091 |
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