Comparative effects of incretin-based therapy on early-onset diabetic nephropathy in rats : Role of TNF-α, TGF-β and c-caspase-3
Copyright © 2021 Elsevier Inc. All rights reserved..
AIMS: Diabetic nephropathy, a major threat to diabetic patients, is considered as the main reason for end-stage renal disease. Fortunately, incretin-based therapy has been aroused as considerable source to attenuate diabetic renal damage. This study aimed to investigate whether superior protective effects on the progression of diabetic kidney are exerted by glucagon-like peptide-1 analog, exenatide, or dipeptidyl peptidase-4 inhibitor, sitagliptin.
MATERIALS AND METHODS: Male Wistar rats were fed high-fat diet for 2 weeks followed by injection of low dose streptozotocin to induce type 2 diabetes mellitus. Four weeks after induction of diabetes, diabetic rats were administered vehicle, exenatide (5 μg/kg/day, SC) or sitagliptin (10 mg/kg/day, orally) for 4 weeks.
KEY FINDINGS: Different incretin mimetic agents improved renal function as evident by significant decreases in serum creatinine and urea levels with decline in urinary microalbuminuria and marked improvement in histological alterations. Both treated diabetic rats also exhibited a significant improvement in metabolic intolerance with more pronounced effect of exenatide on glucose regulation. Ameliorated renal oxidative stress alongside significant downregulation in transforming growth factor-beta, tumor necrosis factor-alpha and cleaved-caspase-3 protein expressions in renal tissues were recorded in treated diabetic rats.
SIGNIFICANCE: Administration of either exenatide or sitagliptin showed ameliorative effects on early diabetic nephropathy without notable differences between their renal protective effects. However, further clinical studies are still required to ensure their comparative promising effects on the management of renal complication of diabetes.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:278 |
|---|---|
| Enthalten in: |
Life sciences - 278(2021) vom: 01. Aug., Seite 119624 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Habib, Heba A [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.06.2021 Date Revised 21.06.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.lfs.2021.119624 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM325553858 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM325553858 | ||
| 003 | DE-627 | ||
| 005 | 20231225192704.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.lfs.2021.119624 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1085.xml |
| 035 | |a (DE-627)NLM325553858 | ||
| 035 | |a (NLM)34004254 | ||
| 035 | |a (PII)S0024-3205(21)00610-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Habib, Heba A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Comparative effects of incretin-based therapy on early-onset diabetic nephropathy in rats |b Role of TNF-α, TGF-β and c-caspase-3 |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.06.2021 | ||
| 500 | |a Date Revised 21.06.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a AIMS: Diabetic nephropathy, a major threat to diabetic patients, is considered as the main reason for end-stage renal disease. Fortunately, incretin-based therapy has been aroused as considerable source to attenuate diabetic renal damage. This study aimed to investigate whether superior protective effects on the progression of diabetic kidney are exerted by glucagon-like peptide-1 analog, exenatide, or dipeptidyl peptidase-4 inhibitor, sitagliptin | ||
| 520 | |a MATERIALS AND METHODS: Male Wistar rats were fed high-fat diet for 2 weeks followed by injection of low dose streptozotocin to induce type 2 diabetes mellitus. Four weeks after induction of diabetes, diabetic rats were administered vehicle, exenatide (5 μg/kg/day, SC) or sitagliptin (10 mg/kg/day, orally) for 4 weeks | ||
| 520 | |a KEY FINDINGS: Different incretin mimetic agents improved renal function as evident by significant decreases in serum creatinine and urea levels with decline in urinary microalbuminuria and marked improvement in histological alterations. Both treated diabetic rats also exhibited a significant improvement in metabolic intolerance with more pronounced effect of exenatide on glucose regulation. Ameliorated renal oxidative stress alongside significant downregulation in transforming growth factor-beta, tumor necrosis factor-alpha and cleaved-caspase-3 protein expressions in renal tissues were recorded in treated diabetic rats | ||
| 520 | |a SIGNIFICANCE: Administration of either exenatide or sitagliptin showed ameliorative effects on early diabetic nephropathy without notable differences between their renal protective effects. However, further clinical studies are still required to ensure their comparative promising effects on the management of renal complication of diabetes | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a C-Caspase-3 | |
| 650 | 4 | |a Diabetic nephropathy | |
| 650 | 4 | |a Exenatide | |
| 650 | 4 | |a Incretin-based therapy | |
| 650 | 4 | |a Sitagliptin | |
| 650 | 4 | |a TGF-β | |
| 650 | 4 | |a TNF-α | |
| 650 | 7 | |a Incretins |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a Caspase 3 |2 NLM | |
| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 700 | 1 | |a Heeba, Gehan H |e verfasserin |4 aut | |
| 700 | 1 | |a Khalifa, Mohamed M A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Life sciences |d 1965 |g 278(2021) vom: 01. Aug., Seite 119624 |w (DE-627)NLM000007579 |x 1879-0631 |7 nnns |
| 773 | 1 | 8 | |g volume:278 |g year:2021 |g day:01 |g month:08 |g pages:119624 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.lfs.2021.119624 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 278 |j 2021 |b 01 |c 08 |h 119624 | ||