Interação entre testosterona e atividade mastocitária no desenvolvimento da fibrose renal induzida por obstrução ureteral em ratos wistar

Abstract

Mast cells are a group of multifunctional cells derived from hematopoietic stem cells, under the influence of stem cell factor. Studies have found evidence that reinforce the importance of these cells in the development of renal fibrosis. These studies report that intrarenal collagen deposition was significantly lower in mice deficient in mast cells, when compared to non-deficient controls, 7 and 14 days after ureteric obstruction. Other researches described that increased deposition of collagen fibers in kidneys with induced ureteral obstruction is more intense in males than females; they have also noticed that orchiectomy inhibited the development of renal fibrosis associated with ureteral obstruction. Thus, the present study aimed to: (i) assess the number of mast cells, the expression of α-actin, PCNA and the level of fibrosis in kidneys of animals underwent ureteral obstruction pretreated with sodium cromoglycate (an inhibitor of mast cell degranulation) or saline; (ii) to evaluate whether orchiectomy and testosterone administration alters the pattern of renal changes induced in the experimental model. To do so, each animal remained 21 days in trial, and it is considered day 0 (zero) the day of the beginning of the experiments. On this day the animals were subjected to a false-operation or orchiectomy. On the 7th day, the animals were subjected to a false-operation or ureteral obstruction. After 14 days of the obstruction the animals were anesthetized and sacrificed to collect biological material. Hormone replacement began one day after orchiectomy, wich means, on day 1 and the treatment with cromoglycate began on the 5th day. The kidney was fixed, embedded, sectioned and then stained with toluidine blue, in order to quantify mast cells; Picrosirius red, for analysis of collagen; Hematoxylin and eosin for examination of the glomerulus and morphology. In addition, two immunohistochemical analysis were performed: α- actin and PCNA. It was observed a decrease in the glomerulus and the capillary tuft area in the group that was induced renal damage. Furthermore, mast cells had an increased density, while orchiectomy and cromoglycate treatment decreased this effect and the same was observed for collagen. There was also an increase in PCNA + cells in the injured kidney, but only orchiectomy partially blocked this effect. Whilst evaluation of α-actin, cromoglycate and orchiectomy partially diminished the increased expression caused by renal injuries. The present study suggests that there is an interaction between mast cells and testosterone in the development of renal fibrosis model of ureteral obstruction.