Reduction of cardiac and renal dysfunction by new inhibitor of DPP4 in diabetic rats

Alves, Bryelle E.O.; Alencar, Alexandre; Gamba, Luis Eduardo Reina; Trachez, Margarete M.; J, da Silva; Araujo, Josenildo S; Montagnoli, Tadeu L.; Mendes, Luiza V.P.; Pimentel‐Coelho, Pedro M.; Cunha, Valeria do Monti Nascimento; Mendez-Otero, Rosália; Oliveira, Gláucia Maria Moraes de; Lima, Lı́dia Moreira; Barreiro, Eliezer J.; Sudo, Roberto T.; Zapata‐Sudo, Gisele

doi:10.1016/j.pharep.2019.07.005

Cited by 5 publications

(7 citation statements)

References 51 publications

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“…T2DM was induced using a combination of 2-week high-fat diet (Research Diet D12492 60 kcal% fat, USA), followed by a low dose (35 mg/kg) of streptozotocin (STZ, Sigma Chemical Co., St. Louis, MO) intraperitoneal injection and continued a highfat diet for another 2 weeks (19). The fasting blood glucose was measured before STZ injection and 2 weeks after STZ injection by using a glucometer (Johnson & Johnson Co., New Brunswick, NJ, USA).…”

Section: T2dm Inductionmentioning

confidence: 99%

Adiponectin-Transfected Endothelial Progenitor Cells Have Protective Effects After 2-Hour Middle-Cerebral Artery Occlusion in Rats With Type 2 Diabetes Mellitus

Wang

Zhang

et al. 2021

Front. Neurol.

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Objectives: This present study aimed to examine the effects of adiponectin-transfected endothelial progenitor cells (LV-APN-EPCs) on cerebral ischemia–reperfusion injury in rats with type 2 diabetes mellitus (T2DM) and to explore the underlying mechanisms.Methods: Seventy male Sprague–Dawley rats with T2DM were randomly divided into sham, phosphate-buffered saline (PBS), LV-APN-EPCs, LV-EPCs, and EPCs groups. Transient middle cerebral artery occlusion (MCAO) was induced by the intraluminal suture method. After 1 h of reperfusion, the five interventions were performed by tail-vein injections. The modified neurological severity score (mNSS) was used to assess neurological function before and on days 1, 7, and 14 after MCAO. After 14 days, magnetic resonance imaging scanning, hematoxylin and eosin staining, terminal dUTP nick-end labeling staining, Western blotting analysis, cluster of differentiation (CD) 31 immunofluorescence, and enzyme-linked immunosorbent assay were used to evaluate infarct rate, morphological damage, cell apoptosis, and microvessel density.Results: Compared with PBS, LV-EPCs, and EPCs groups, the LV-APN-EPCs group showed significantly lower mNSS score, lower infarct rate, and less morphological damage (all P < 0.05). In addition, compared with other groups, the LV-APN-EPCs group had significantly increased levels of B cell lymphoma/leukemia-2 (Bcl-2) protein, CD31+ microvessels, endothelial nitric oxide synthase, and vascular endothelial growth factor, and decreased levels of Bcl-2-associated X protein and neuronal apoptosis in the peri-infarct cortex (all P < 0.05).Conclusion: These results suggest that LV-APN-EPCs exert protective effects against cerebral ischemia–reperfusion injury in T2DM rats by increasing angiogenesis.

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Section: T2dm Inductionmentioning

confidence: 99%

Adiponectin-Transfected Endothelial Progenitor Cells Have Protective Effects After 2-Hour Middle-Cerebral Artery Occlusion in Rats With Type 2 Diabetes Mellitus

Wang

Zhang

et al. 2021

Front. Neurol.

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“…Cardiac function and structure were assessed both before (baseline) and after treatment (endpoint) as previously reported. 17…”

Section: Biochemical Analysismentioning

confidence: 99%

“…Interstitial cell number and collagen content were analyzed in hematoxylin and eosin and picro-Sirius red stained sections, respectively, in 15-20 fields of LV using Fiji software. 17,25…”

Section: Histomorphometric Analysismentioning

confidence: 99%

“…Heart homogenates were prepared for protein expression analysis by Western blot as previously published. 17 Briefly, tissues were harvested, stored in lysis buffer with protease inhibitors, and frozen in liquid nitrogen. Heart samples were homogenized and centrifuged at 1000×g.…”

Section: Membrane Preparations and Western Blot Analysismentioning

confidence: 99%

“…16 The N-acylhydrazone (NAH) scaffold is regarded as a privileged structure because it is found in many bioactive compounds, and examples of anti-inflammatory, antihypertensive, and anti-hyperglycemic NAH have already been reported. [17][18][19] Compound (E)-3-amino-N'-((3,5dimethyl-1-phenyl-1H-pyrazol-4-yl)methylene)benzofuran-2-carbohydrazide (LASSBio-2090; Figure 1) is a newly synthetized NAH initially conceived to fulfill the main structural requirements of dipeptidyl peptidase 4 (DPP4) inhibitors. 20 LASSBio-2090 was designed using NAH as a linker between 3-aminobenzofuran and 3.5dimethylphenylpyrazole groups, both generated from the LASSBio-1425 structure by applying bioisosterism and molecular simplification strategies, respectively.…”

Section: Introductionmentioning

confidence: 99%

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<p>New Benzofuran <em>N</em>-Acylhydrazone Reduces Cardiovascular Dysfunction in Obese Rats by Blocking TNF-Alpha Synthesis</p>

Costa

Montagnoli²,

Silva³

et al. 2020

DDDT

Self Cite

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Introduction Diabetic obese patients are susceptible to the development of cardiovascular disease, including hypertension and cardiac dysfunction culminating in diabetic cardiomyopathy (DC), which represents a life-threatening health problem with increased rates of morbidity and mortality. The aim of the study is to characterize the effects of a new benzofuran N -acylhydrazone compound, LASSBio-2090, on metabolic and cardiovascular alterations in Zucker diabetic fatty (ZDF) rats presenting DC. Methods Male non-diabetic lean Zucker rats (ZL) and ZDF rats treated with vehicle (dimethylsulfoxide) or LASSBio-2090 were used in this study. Metabolic parameters, cardiovascular function, left ventricle histology and inflammatory protein expression were analyzed in the experimental groups. Results LASSBio-2090 administration in ZDF rats reduced glucose levels to 85.0 ± 1.7 mg/dL ( p < 0.05). LASSBio-2090 also lowered the cholesterol and triglyceride levels from 177.8 ± 31.2 to 104.8 ± 5.3 mg/dL and from 123.0 ± 11.4 to 90.9 ± 4.8 mg/dL, respectively, in obese diabetic rats ( p < 0.05). LASSBio-2090 normalized plasma insulin, insulin sensitivity and endothelial function in aortas from diabetic animals ( p < 0.05). It also enhanced systolic and diastolic left-ventricular function and reverted myocardial remodeling by blocking the threefold elevation of TNF-α levels in hearts from ZDF rats. Conclusion LASSBio-2090 alleviates metabolic disturbance and cardiomyopathy in an obese and diabetic rat model, thus representing a novel strategy for the treatment of cardiovascular complications in obesity-associated type 2 diabetes mellitus.

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Cardiovascular protection by DPP-4 inhibitors in preclinical studies: an updated review of molecular mechanisms

Zakaria

Tawfeek

Hassanin

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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Dipeptidyl peptidase 4 (DPP4) inhibitors are a class of antidiabetic medications that cause glucose-dependent increase in incretins in diabetic patients. One of the two incretins, glucagon-like peptide-1 (GLP-1), beside its insulinotropic activity, has been studied for extra pancreatic effects. Most of DPP4 inhibitors (DPP4i) have been investigated in in vivo and in vitro models of diabetic and nondiabetic cardiovascular diseases including heart failure, hypertension, myocardial ischemia or infarction, atherosclerosis, and stroke. Results of preclinical studies proved prominent therapeutic potential of DPP4i in cardiovascular diseases, regardless the presence of diabetes. This review aims to present an updated summary of the cardiovascular protective and therapeutic effects of DPP4 inhibitors through the past 5 years focusing on the molecular mechanisms beneath these effects. Additionally, based on the results summary presented here, future studies may be conducted to elucidate or illustrate some of these findings which can add clinical benefits towards management of diabetic cardiovascular complications.

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Reduction of cardiac and renal dysfunction by new inhibitor of DPP4 in diabetic rats

Cited by 5 publications

References 51 publications

Adiponectin-Transfected Endothelial Progenitor Cells Have Protective Effects After 2-Hour Middle-Cerebral Artery Occlusion in Rats With Type 2 Diabetes Mellitus

Adiponectin-Transfected Endothelial Progenitor Cells Have Protective Effects After 2-Hour Middle-Cerebral Artery Occlusion in Rats With Type 2 Diabetes Mellitus

<p>New Benzofuran <em>N</em>-Acylhydrazone Reduces Cardiovascular Dysfunction in Obese Rats by Blocking TNF-Alpha Synthesis</p>

Cardiovascular protection by DPP-4 inhibitors in preclinical studies: an updated review of molecular mechanisms

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