Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 14, Issue -, Pages 3337-3350Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S258459
Keywords
type 2 diabetes mellitus; diabetic cardiomyopathy; anti-TNF-alpha therapy; cardiac dysfunction; heart hypertrophy; Zucker diabetic fatty rat
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Instituto Nacional de Ciencia e Tecnologia de Farmacose Medicamentos (INCT-INOFAR)
- Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO)
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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-alpha 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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