The efficacy of chronic zinc oxide nanoparticles using on testicular damage in the streptozotocin-induced diabetic rat model

Testicular impairment is a common complication of Diabetes mellitus (DM). Zinc Oxide Nanoparticles (ZnO NPs) are a novel agent for Zn delivery with antidiabetic and antioxidant activities. However, few reports were recorded on it. The current study aimed to investigate the possible ameliorating effect of ZnO NPs treatment on testicular tissues alterations in streptozotocin (STZ)-induced diabetic rats. Therefore, thirty mature male Wistar rats were divided into three main groups: Control group (n?=?18) was subdivided equally into three subgroups (negative control, vehicle and ZnO NPs), Diabetic group (n?=?6) and ZnO NPs-treated diabetic group (n?=?6). Induction of diabetes was done by a single intraperitoneal injection of STZ (60?mg/kg bw). The rats were orally treated by ZnO NPs (10?mg/kg bw) for 30 constitutive days. At the end of the experiment, blood glucose and serum testosterone levels were measured. Also, testicular tissues were obtained for histopathological investigations and immunohistochemical staining with anti-PCNA (proliferating cell marker), anti-ssDNA (apoptotic cell marker), anti-SOX9 (Sertoli cell marker), anti-Stella (spermatogonia marker), anti-STRA8 (preleptotene and early-leptotene spermatocytes marker), anti-DMC1 (leptotene and zygotene spermatocytes marker), anti-Dnmt3a (a marker for cells under DNA methylation) and anti-α-SMA (peritubular myoid cell marker). The biochemical analysis revealed that diabetes resulted in a significant elevation in blood glucose level and a reduction in serum testosterone level. Moreover, histopathological investigations revealed disorganized seminiferous epithelium and sever hyalinization with vacuolization of the testicular interstitium containing Leydig cells. The immunohistochemical findings support spermatogenesis impairment in the diabetic group. However, ZnO NPs treatment restores architecture of seminiferous epithelium and Leydig cells. Furthermore, more PCNA, SOX9, Stella, STRA8, DMC1 and Dnmt3a immunopositive cells with an improvement of peritubular α-SMA immunopositive expression, as well as few ssDNA-immunopositive cells were detected in the seminiferous epithelium. This study suggested the possible protective role of orally administered ZnO NPs on testicular alterations in the STZ-induced diabetic group via steroidogenesis and spermatogenesis enhancement. In addition, further researches are acquired for evaluation mechanism of ZnO NPs treatment via oral or parenteral routes in a dose-dependent manner to identify the more effective route and dose in the treatment of testicular diabetic complications.     

The effects of water immersion and restraint stress on the expressions of apelin,apelin receptor (APJR) and apoptosis rate in the rat heart

Apelin has been identified as an endogenous ligand of the orphan G-protein-coupled apelin receptor (APJR). These receptors are widely expressed in the central nervous system and periphery and play a role in the regulation of fluid and glucose homeostasis, feeding behavior, vessel formation, cell proliferation and immunity. We aimed to investigate whether water immersion and restraint stress have effects on apelin and APJR expression and apoptosis in heart tissue of male Wistar rats. The cardiac tissues were obtained from control, water immersion and restraint stress (WIRS) and apelin antagonist (F13A) + WIRS groups of rats and embedded in paraffin wax. Immunohistochemical staining methods were used to localize apelin, APJR and TUNEL immunopositive cells. H-SCORE was used for semi-quantitative determinations. Apelin protein levels were determined by Western blot in the cardiac tissues and plasma corticosteroid levels were measured by enzyme immunoassay (EIA). Apelin immunolocalization was found especially in endothelial cells and mast cells and faintly in cardiomyocytes, APJR immunostaining was shown in endothelial cells and cardiomyocytes, and TUNEL reaction was observed in endothelial cells and in some fibroblasts. Apelin expression was significantly increased in the WIRS and F13A + WIRS groups compared to the control group. The APJR reaction was similar in all groups. The number of TUNEL-positive cells was significantly higher in the F13A + WIRS group than that of the control group. Our study showed that WIRS for 6 h increased plasma corticosterone levels and cardiac apelin expression in rats. The increased levels of apelin inhibited stress-induced apoptosis in heart. These results may be important for the therapeutic approach to a variety of stress-related heart disease.