Novel Therapies Targeting Cardioprotection and Regeneration.

Cardiovascular disease is the leading cause of death worldwide. The heart is susceptible to pathologies that impact the myocardium directly, such as myocardial infarction and consequent heart failure, as well as conditions with indirect cardiac effects, such as cancer treatment-related cardiotoxicity. As the contractile cells of the heart, cardiomyocytes are essential for normal cardiac function. Various stress stimuli may result in transient damage or cell death in cardiomyocytes through apoptosis, necrosis or maladaptive autophagy. Moreover, cardiomyocytes are unable to regenerate; thus, lost cells are replaced with fibrotic tissue, with a potentially severe impact on myocardial function. Several therapeutic agents and strategies to reduce cardiomyocyte damage are currently available. This manuscript reviews the state of the art regarding novel cardioprotective endogenous peptides, such as neuregulin-1, angiotensin-(1-9), growth/differentiation factor-11, growth/differentiation factor- 15 and insulin-like growth factor-1. We discuss their protective effects and therapeutic potential in cardiovascular diseases and the current challenges to harnessing their full cardioprotective power. We also explore targeting of exosomes as a cardioprotective approach along with the therapeutic potential of cardiac regeneration strategies. Further advances associated with these molecules and cardioprotective approaches may provide more effective therapies to attenuate or prevent cardiomyocyte death, thereby preserving the myocardium.

New Molecular Insights of Insulin in Diabetic Cardiomyopathy.

Type 2 diabetes mellitus (T2DM) is a highly prevalent disease worldwide. Cardiovascular disorders generated as a consequence of T2DM are a major cause of death related to this disease. Diabetic cardiomyopathy (DCM) is characterized by the morphological, functional and metabolic changes in the heart produced as a complication of T2DM. This cardiac disorder is characterized by constant high blood glucose and lipids levels which eventually generate oxidative stress, defective calcium handling, altered mitochondrial function, inflammation and fibrosis. In this context, insulin is of paramount importance for cardiac contractility, growth and metabolism and therefore, an impaired insulin signaling plays a critical role in the DCM development. However, the exact pathophysiological mechanisms leading to DCM are still a matter of study. Despite the numerous questions raised in the study of DCM, there have also been important findings, such as the role of micro-RNAs (miRNAs), which can not only have the potential of being important biomarkers, but also therapeutic targets. Furthermore, exosomes also arise as an interesting variable to consider, since they represent an important inter-cellular communication mechanism and therefore, they may explain many aspects of the pathophysiology of DCM and their study may lead to the development of therapeutic agents capable of improving insulin signaling. In addition, adenosine and adenosine receptors (ARs) may also play an important role in DCM. Moreover, the possible cross-talk between insulin and ARs may provide new strategies to reverse its defective signaling in the diabetic heart. This review focuses on DCM, the role of insulin in this pathology and the discussion of new molecular insights which may help to understand its underlying mechanisms and generate possible new therapeutic strategies.

Therapeutic dose of Ginkgo biloba extract 761 may alter the urine excretion of Wistar rats

Wistar rats (n=20) were divided in two groups: G1 received 2 mg/kg of GBE (Ginkgo biloba extract 761), whereas G2 received the same volume of a sodium chloride solution (0.9%), both for 10 days. After a 7-day interval, the treatment was repeated for 8 days. Urine volume and food and water intake were measured daily during this protocol. Histological assessments were performed. No significant difference (p>0.05) was observed in food and water intake of animals during treatment with GBE. Animals who received GBE had a smaller urine volume and increase of weight with a significance difference (p<0.05) during the first and second exposure period. No histological alteration was observed in tissues, except for the kidney of the experimental group, which revealed a higher concentration of red cells in the glomerulus with a strong staining for Vascular Endothelial Growth Factor (VEGF). The introduction of GBE (therapeutic dose) in health rats may promote alterations in the physiology of the kidney, but no sufficient to modify the glomerulus architecture, including at ultra structural level (electron microscopy).

Evaluation of the acute toxicity of dolabelladienotriol, a potential antiviral from the brown alga Dictyota pfaffii, in BALB/c mice

Dolabelladienotriol is a product extracted from the brown marine alga Dictyota pfaffii from Brazil that has been shown to have antiviral activity and low cytotoxicity. Our studies have evaluated the acute toxicity of dolabelladienotriol in BALB/c mice for ten days after administration of a single dose. Among the parameters considered were behavior, weight, biochemical and histological analyses of blood samples taken at three different times (Bs.0, Bs.1 and Bs.2) and optical microscopic examination of organs like liver, kidney, stomach and small intestine. Mice deaths were not observed at any dose during the ten day period. There were some changes in the biochemical analysis results for urea nitrogen (BUN) and alanine aminotransferase (ALT), but the changes were not significantly different from the reference levels of the animals before administration of the substance. Histological analyses of tissues were very similar for all animals. The alterations in liver and kidney tissues did not affect the animals´ behavior at any concentration, not even at 50 mg/kg, where the most significant changes in tissues were seen. This study indicates that dolabelladienotriol has low toxicity in administered dose range.