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New Benzofuran N-Acylhydrazone Reduces Cardiovascular Dysfunction in Obese Rats by Blocking TNF-Alpha Synthesis

Gizele Cabral Costa1, Tadeu Lima Montagnoli2, Jaqueline Soares Da Silva2

  • 1Programa de Pós-Graduação em Medicina (Cardiologia), Instituto do Coração Edson Saad, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Drug Design, Development and Therapy
|September 5, 2020
PubMed

Insights

A new compound, LASSBio-2090, effectively treats diabetic cardiomyopathy (DC) and metabolic issues in obese diabetic rats. This research offers a promising new strategy for managing cardiovascular complications in type 2 diabetes.

Area of Science:

  • Pharmacology and Toxicology
  • Cardiovascular Medicine
  • Endocrinology and Metabolism

Background:

  • Obese diabetic patients face high risks of cardiovascular disease, including hypertension and diabetic cardiomyopathy (DC).
  • Diabetic cardiomyopathy (DC) is a severe condition leading to increased morbidity and mortality.
  • There is a critical need for effective treatments targeting cardiovascular complications in type 2 diabetes.

Purpose of the Study:

  • To investigate the effects of a novel benzofuran N-acylhydrazone compound, LASSBio-2090.
  • To assess LASSBio-2090's impact on metabolic and cardiovascular alterations in Zucker diabetic fatty (ZDF) rats with DC.

Main Methods:

  • Utilized male non-diabetic lean Zucker rats (ZL) and ZDF rats.
  • Administered vehicle (dimethylsulfoxide) or LASSBio-2090 to experimental groups.
  • Analyzed metabolic parameters, cardiovascular function, left ventricle histology, and inflammatory protein expression.

Main Results:

  • LASSBio-2090 significantly reduced glucose levels (to 85.0 ± 1.7 mg/dL) and improved lipid profiles in ZDF rats.
  • The compound normalized plasma insulin, enhanced insulin sensitivity, and improved endothelial function in diabetic aortas.
  • LASSBio-2090 improved left-ventricular systolic and diastolic function, and reverted myocardial remodeling by reducing TNF-α.

Conclusions:

  • LASSBio-2090 demonstrates efficacy in alleviating metabolic disturbances and cardiomyopathy in an obese diabetic rat model.
  • This compound represents a novel therapeutic strategy for cardiovascular complications associated with obesity and type 2 diabetes.
  • Further research into LASSBio-2090 could lead to new treatments for diabetic cardiomyopathy.
Abstract

Keywords:
Zucker diabetic fatty ratanti-TNF-α therapycardiac dysfunctiondiabetic cardiomyopathyheart hypertrophytype 2 diabetes mellitus

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