Maternal exposure to glyphosate-based herbicide causes changes in the vascular function of offspring adult rats.

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their offspring, focusing on the influence of age and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of glyphosate herbicide-based (O-GHB) and controls (O-CON) rats at 3, 6, and 12 months of age. O-GHB groups showed no changes in arterial blood pressure or aorta histological analysis. Relaxation to acetylcholine was reduced in O-GHB than O-CON. Acute TEMPOL increased relaxation to acetylcholine in O-GHB at 6 and 12 months of age. The aorta from O-GHB was hyperactive to phenylephrine only at 6 months of age. Preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GHB. TEMPOL similarly reduced phenylephrine response. This effect was prevented by L-NAME. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that although no changes in cardiac or histological parameters have been demonstrated, the current levels considered safe for exposure to glyphosate deserve further investigation, especially during pregnancy.

Multifunctional hydroxyapatite with potential for application in theranostic nanomedicine.

Although several materials are being studied for the development of theranostic systems, factors such as high costs, low yield, stability of nanoparticles (NPs) and toxicity-related issues hinder their application in medicine. Thus, this paper introduces the synthesis of a theranostic system composed of hydroxyapatite (HAp) functionalized with europium (Eu3+) and zinc oxide (ZnO) NPs, resulting in a low-cost material that presents biocompatibility, luminescence, antibacterial activity and whose synthesis method is simple. The Eu3+ - doped HAp was obtained through the precipitation method and the functionalization with ZnO occurred in the subsequent stage through the solid-state reaction method. The resulting material, [Ca9.5Eu0.5(PO4)6(OH)2@ZnO], was characterized by several techniques where the photoluminescence spectrum exhibited sharp peaks at the 4fN â†’ 4fN transitions typical of Eu3+ ions, while tests with bacteria proved its antibacterial property. The crystal structure obtained by X-ray diffraction confirmed HAp as the major phase. The multifunctional HAp (HAp:Eu@ZnO) was considered as hemocompatible, exhibiting an in vitro hemolysis ratio of 1.85 (±0.2) %, and its loading potential, tested for two antitumor drugs, showed an adsorption capacity of 43.0 ± 3.6% for 5-Fluorouracil and 84.0 ± 4.0% for curcumin. The cytotoxicity of the system as well as its use as a support for drugs was analyzed through in vitro assays with tumor cells from sarcoma 180 in mice. The results confirmed that HAp:Eu@ZnO is non-toxic to cells and its potential for antineoplastic vectorization is increased by cell internalization due to endocytosis, with up to 39.0% of cancer cell deaths having been observed at the concentrations and period evaluated.

Gene expression changes associated with myocarditis and fibrosis in hearts of mice with chronic chagasic cardiomyopathy.

Chronic chagasic cardiomyopathy is a leading cause of heart failure in Latin American countries. About 30% of Trypanosoma cruzi-infected individuals develop this severe symptomatic form of the disease, characterized by intense inflammatory response accompanied by fibrosis in the heart. We performed an extensive microarray analysis of hearts from a mouse model of this disease and identified significant alterations in expression of approximately 12% of the sampled genes. Extensive up-regulations were associated with immune-inflammatory responses (chemokines, adhesion molecules, cathepsins, and major histocompatibility complex molecules) and fibrosis (extracellular matrix components, lysyl oxidase, and tissue inhibitor of metalloproteinase 1). Our results indicate potentially relevant factors involved in the pathogenesis of the disease that may provide new therapeutic targets in chronic Chagas disease.

Synthesis, docking, and in vitro activity of thiosemicarbazones, aminoacyl-thiosemicarbazides and acyl-thiazolidones against Trypanosoma cruzi.

A novel series of thiosemicarbazone and aminoacyl-thiazolidones derivatives were synthesized. Their structure suggests that these compounds could have anti-Trypanosoma cruzi activity. Biological evaluation indicates that some of these compounds are able to inhibit the growth of T. cruzi in concentrations non-cytotoxic to mammalian cells. Docking studies were carried out in order to investigate the binding pattern of these compounds for the T. cruzi cruzain (TCC) protein, and these showed a significant correlation with experimental data.