Background Functional receptors for leptin were described on the surface of cardiomyocytes, and there was a prohypertrophic effect with high concentrations of the cytokine. Therefore, leptin could be a link between obesity and the prevalence of cardiovascular diseases. On the other hand, a deleterious effect of leptin on mitochondrial performance was described, which was also associated with the evolution of cardiac hypertrophy to heart failure. The goal of our study was to analyze the effect of the exposure of rat hearts to a high concentration of leptin on cardiac and mitochondrial function. Methods Rat hearts were perfused continuously with or without 3.1 nM leptin for 1, 2, 3, or 4 hours. Homogenates and mitochondria were prepared by centrifugation and analyzed for cardiac actin, STAT3, and pSTAT3 by Western blotting, as well as for mitochondrial oxidative phosphorylation, membrane potential, swelling, calcium transport, and content of oxidized lipids. Results In our results, leptin induced an increased rate-pressure product as a result of increased heart rate and contraction force, as well oxidative stress. In addition, mitochondrial dysfunction expressed as a loss of membrane potential, decreased ability for calcium transport and retention, faster swelling, and less respiratory control was observed. Conclusions Our results support the role of leptin as a deleterious factor for cardiac function and indicates that mitochondrial dysfunction could be a trigger for cardiac hypertrophy and failure.
BACKGROUND: Selective etching of silica nanoparticles allows the formation of mesoporosity, increasing the loading capability of nanoparticles for further drug release applications. By coating such mesoporous silica nanoparticles with biocompatible pH-sensitive polymers, the selectivity of drug delivery systems can be enhanced and adverse side effects can be minimized. So far, selectively etched silica has been scarcely explored for drug encapsulation.RESULTS: Spherical particles with sizes ranging from 200 to 500 nm were obtained by the Stöber method. Selective etching was performed at two different aging times, leading to the formation of uniform pores with specific surface areas of 115 and 150 m 2 g −1 for 0 and 14 h of aging respectively. X-ray analysis demonstrated the formation of ordered materials, while the hydrodynamic sizes were around 300 nm. cis-Diamminedichloroplatinum(II) was encapsulated in etched silica nanoparticles and coated with chitosan, and the drug was released at pH 5. In vitro evaluation of the nanoparticles was performed in U-373 cells, reaching around 40% of cell death. CONCLUSION: Selective etching of nanoparticles allowed the obtaining of homogeneous coated hybrid nanoparticles and an efficient pH-sensitive drug delivery hybrid system for the release of chemotherapeutic agent with enhanced activity against U-373 human glioblastoma cells.
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