Enalapril e captopril revertem o edema e a hiperplasia renais causados pelo antimoniato de N-metilglucamina em camundongos C57BL/6

ABSTRACT The aim of this study was to verify whether enalapril and captopril would reverse the renal damage caused by N-methylglucamine antimoniate in C57BL/6 mice. We used inbred C57BL/6 female mice, obtained from the Oswaldo Cruz Foundation (FIOCRUZ), Salvador, BA. The mice were divided into four groups as follows: Group1: received saline by the intramuscular (IM) route; Group 2: received N-methylglucamine antimonate (IM); Group 3: received N-methylglucamine antimoniate and captopril; Group 4: was treated with N-methylglucamine antimoniate and enalapril. Both enalapril and captopril were orally administered in drinking water (ad libitum). After 30 days of treatment, the animals were sacrificed and their kidneys were collected for histological analysis which showed that enalapril completely reversed the edema, the podocytes hyperplasia and nucleus of the epithelial cells in the proximal convoluted tubules caused by N-methylglucamine antimoniate. On the other hand, the captopril treatment partially inhibited kidney harmful effects caused by N-metilgucamina antimoniate. Taken together, we would conclude that enalapril and captopril reverse edema and renalhyperplasia caused by N-methylglucamine antimonate in mice

A low-protein, high-carbohydrate diet increases browning in perirenal adipose tissue but not in inguinal adipose tissue

Objective The aim of this study was to evaluate the browning and origin of fatty acids (FAs) in the maintenance of triacylglycerol (TG) storage and/or as fuel for thermogenesis in perirenal adipose tissue (periWAT) and inguinal adipose tissue (ingWAT) of rats fed a low-protein, high-carbohydrate (LPHC) diet. Methods LPHC (6% protein, 74% carbohydrate) or control (C; 17% protein, 63% carbohydrate) diets were administered to rats for 15 d. The tissues were stained with hematoxylin and eosin for histologic analysis. The content of uncoupling protein 1 (UCP1) was determined by immunofluorescence. Levels of T-box transcription factor (TBX1), PR domain containing 16 (PRDM16), adipose triacylglycerol lipase (ATGL), hormone-sensitive lipase, lipoprotein lipase (LPL), glycerokinase, phosphoenolpyruvate carboxykinase (PEPCK), glucose transporter 4, β3-adrenergic receptor (AR), β1-AR, protein kinase A (PKA), adenosine-monophosphate-activated protein kinase (AMPK), and phospho-AMPK were determined by immunoblotting. Serum fibroblast growth factor 21 (FGF21) was measured using a commercial kit (Student's t tests, P < 0.05). Results The LPHC diet increased FGF21 levels by 150-fold. The presence of multilocular adipocytes, combined with the increased contents of UCP1, TBX1, and PRDM16 in periWAT of LPHC-fed rats, suggested the occurrence of browning. The contents of β1-AR and LPL were increased in the periWAT. The ingWAT showed higher ATGL and PEPCK levels, phospho-AMPK/AMPK ratio, and reduced β3-AR and PKA levels. Conclusion These findings suggest that browning occurred only in the periWAT and that higher utilization of FAs from blood lipoproteins acted as fuel for thermogenesis. Increased glycerol 3-phosphate generation by glyceroneogenesis increased FAs reesterification from lipolysis, explaining the increased TG storage in the ingWAT. © 2017 Elsevier Inc

The annexin 1-/- mouse: phenotypic studies

We investigated the phenotype of Anx-A1-/- mice and studied the appearance of the gene expression during embryonic and postnatal development. Anx-A1-/- mice are fertile and there were no apparent differences in litter sizes or other breeding statistics when compared to litter mate Anx-A1+/+ controls. The null mice grew at the same rate as the Anx-A1+/+ controls and appeared normal at all ages. Plasma sodium, potassium and possibly calcium were slightly elevated in an apparently genotype-dependent fashion, although all these differences were probably still within the normal range. The liver enzyme ALT was significantly elevated in the Anx-A1-/- mice but most other aspects of blood chemistry were no different. In terms of post mortem pathology, there were few exceptional findings although genotype related changes were seen in the weight of the liver, heart, thymus, pancreas, pituitary gland and kidney at necroscopy. Examination by western blotting of the tissue concentrations of other members of the annexin family revealed that Anx-A1 gene deletion lead, in some organs (e.g. lung and thymus), to changes in the tissue concentration of other annexins as well as the pro-inflammatory enzymes COX-2, cPLA2 and iNOS. There was some evidence of a sexual dimorphism in this effect. Anx-A1 gene expression was first detected at embryonic day 10.5 in the corneal epithelium. Thereafter, the skin, bone and respiratory tract were among several sites that displayed strong gene expression during embryonic development whereas the brain and the heart exhibited little gene expression at any developmental stage. These findings are discussed in relation to several proposed roles for the protein

Supplementary Material for: 3,4-Methylenedioxymethamphetamine (Ecstasy) Decreases Inflammation and Airway Reactivity in a Murine Model of Asthma

<i>Objective:</i> 3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is a synthetic drug used recreationally, mainly by young people. It has been suggested that MDMA has a Th cell skewing effect, in which Th1 cell activity is suppressed and Th2 cell activity is increased. Experimental allergic airway inflammation in ovalbumin (OVA)-sensitized rodents is a useful model to study Th2 response; therefore, based on the Th2 skewing effect of MDMA, we studied MDMA in a model of allergic lung inflammation in OVA-sensitized mice. <i>Methods: </i>We evaluated cell trafficking in the bronchoalveolar lavage fluid, blood and bone marrow; cytokine production; L-selectin expression and lung histology. We also investigated the effects of MDMA on tracheal reactivity in vitro and mast cell degranulation. <i>Results:</i> We found that MDMA given prior to OVA challenge in OVA-sensitized mice decreased leukocyte migration into the lung, as revealed by a lower cell count in the bronchoalveolar lavage fluid and lung histologic analysis. We also showed that MDMA decreased expression of both Th2-like cytokines (IL-4, IL-5 and IL-10) and adhesion molecules (L-selectin). Moreover, we showed that the hypothalamus-pituitary-adrenal axis is partially involved in the MDMA-induced reduction in leukocyte migration into the lung. Finally, we showed that MDMA decreased tracheal reactivity to methacholine as well as mast cell degranulation in situ. <i>Conclusions:</i> Thus, we report here that MDMA given prior to OVA challenge in OVA-sensitized allergic mice is able to decrease lung inflammation and airway reactivity and that hypothalamus-pituitary-adrenal axis activation is partially involved. Together, the data strongly suggest an involvement of a neuroimmune mechanism in the effects of MDMA on lung inflammatory response and cell recruitment to the lungs of allergic animals