Gamma-decanolactone is a monoterpene compound, and its psychopharmacological evaluation in mice revealed that it has a dose-dependent effect on the central nervous system, with hypnotic, anticonvulsant, and hypothermic activity. The aim of the present study was to investigate the effect of gamma-decanolactone on pentylenetetrazole (PTZ)-kindling in mice. Phenobarbital, an antiepileptic drug, was also tested for the purpose of comparison. After the behavioral procedures had been undertaken, the animals were killed and brain tissue was sampled to evaluate DNA damage in the brain using comet assay. The data reported here suggest that the administration of phenobarbital (10 mg/kg) and gamma-decanolactone at 0.3 g/kg, but not at 0.1 g/kg, impairs both the severity and the progression of seizures in the PTZ-kindling model. DNA damage to brain tissue decreased in gamma-decanolactone-treated kindling animals (similar to phenobarbital) as compared to nontreated animals. The results suggest that gamma-decanolactone has dose-dependent anticonvulsant properties, and may also have antiepileptogenic and neuroprotective effects in the PTZ-kindling model.

Angiotensin converting enzyme 2 (ACE2) and its product, angiotensin (1‐7) (Ang (1‐7)), have been shown to protect against renal and cardiovascular dysfunction in animal models of diabetes and hypertension. We found that under baseline conditions, deletion of ACE2 results in a normal mouse phenotype with little or no change in blood pressure and albumin/creatinine excretion in 16 wks old ACE2 knockout (KO) mice compared to wild type (WT) mice. In addition, urinary and renal Ang (1‐7) were not changed suggesting that other factors regulate loss of ACE2. Presence of other peptidases known to form Ang (1‐7), neprilysin (NEP) and angiotensin converting enzyme (ACE), was affirmed using western blot in ACE2KO and WT mice. Activity of NEP and ACE in ACE2KO and WT kidney homogenates was analyzed by mass spectrometry. Results indicate that other proteolytic pathways may be involved in the enzymatic cascade producing Ang (1‐7) thus compensating for ACE2 deficiency. Elucidation of ACE2 independent Ang (1‐7) formation may have clinical implications for treatment of cardiovascular and renal dysfunction. Supported by NIH R01HL093567 and AHA 10PRE4330004 (NMW).

Endostatin (ES) is an antiangiogenic protein that exhibits antitumor activity in animal models. However, the activity observed in animals was not observed in human clinical trials. ES-BAX is a fusion protein composed of two functional domains: ES, which presents specificity and is internalized by activated endothelial cells and the proapoptotic BH3 domain of the protein BAX, a peptide inductor of cellular death when internalized. We have previously shown (Chura-Chambi et al., Cell Death Dis, 5, e1371, 2014) that ES-BAX presents improved antitumor activity in relation to wild-type ES. Secondary and tertiary structures of ES-BAX are similar to ES, as indicated by homology-modeling studies and molecular dynamics simulations. Tryptophan intrinsic fluorescence and circular dichroism spectroscopy corroborate these data. N HSQC NMR indicates that ES-BAX is structured, but some ES residues have suffered chemical shift perturbations, suggesting that the BH3 peptide interacts with some parts of the ES protein. ES and ES-BAX present similar stability to thermal denaturation. The production of stable hybrid proteins can be a new approach to the development of therapeutic agents presenting specificity for tumoral endothelium and improved antitumor effect.