Effects of sunitinib on immunoreactivity of vimentin, E-cadherin and S100 in kidneys of streptozotocin induced diabetic mice.

Diabetes mellitus (DM) affects many organs including kidney. Tyrosine kinase can cause hypoglycemia and sunitinib is an inhibitor of tyrosine kinase. We investigated the possible effects of sunitinib on the kidney of streptozotocin (STZ) induced type 1 diabetic mice. We used 28 CD 1 type male mice divided into four groups of seven. Type 1 diabetes was induced by injection of STZ. Group 1 was the untreated control. Group 2 comprised non-diabetic mice + sunitinib. Both groups 1 and 2 exhibited normal blood glucose levels. Group 3 comprised STZ treated diabetic mice + saline. Group 4 were diabetic mice + sunitinib treatment. Kidneys were removed after 8 weeks. The immunoreactivities of vimentin, E-cadherin and S100 were assessed. Immunostaining of vimentin, E-cadherin and S100 was located in both the glomeruli and tubules of the kidney. We found that the number of vimentin and E-cadherin positive glomeruli and tubules were increased after sunitinib treatment compared to saline treated diabetic mice. The number of vimentin labeled tubules was decreased in the sunitinib treated group compared to diabetic + saline groups. Differences in the number of S100 positive tubules and glomeruli between groups 3 and 4 were not statistically significant. The effect of sunitinib on experimental diabetic mice appears to be related to levels of vimentin, E-cadherin and S100 in the glomeruli and tubules of the kidney, and sunitinib may protect against renal damage from DM.

Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis.

To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p < .001). The mean H-score and AI were significantly higher in VAR group compared with SHAM (p < .001). After losartan administration, mean JS was significantly increased (p < .001) and mean H-score and AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis.

The effects of sunitinib on endometriosis.

The aim of the present study was to evaluate the effect of sunitinib on endometriotic implants and adhesions in a rat endometriosis model. An experimental endometriosis model was created in 21 rats. These rats were randomly divided into three groups: Group 1 (control group, 7 rats) was given no medication; Group 2 (sunitinib group, 7 rats) was given 3 mg/kg per day of oral sunitinib; and Group 3 (danazol group, 7 rats) was given 7.2 mg/kg per day of oral danazol. The volume of endometriotic implants was calculated. The extent and severity of adhesions were evaluated. The groups were compared by the Student's t-test, analysis of variance (ANOVA) and the Mann-Whitney U test. There was no statistically significant difference in the mean volume of endometriotic implants before medication between three groups. The volume of implants and extent, severity, total score of adhesions were significantly decreased after medication in Group 2 and Group 3. We noted that the volume of the endometriotic implants and adhesion formation were decreased both after sunitinib and danazol treatment. As a result, sunitinib seems to be effective for endometriotic peritoneal lesions. The effects of sunitinib in rat models give hope for improving the treatment of human endometriosis and prevention of pain symptoms.

Immunoexpressions of embryonic and nonembryonic stem cell markers (Nanog, Thy-1, c-kit) and cellular connections (connexin 43 and occludin) on testicular tissue in thyrotoxicosis rat model.

In this study, possible thyrotoxicosis-related histological changes in testicular tissues of rats with experimentally induced thyrotoxicosis model were evaluated on cellular connections and stem cell markers. Two experimental groups, thyrotoxicosis and control, each consisting of eight animals were used. Rats in the thyrotoxicosis group were injected intraperitoneally with 3,3',5-triiodo-l-thyronine (50 µg/100 g body weight/day) for 10 days. At the end of the study, animals in both groups were anesthetized, and blood samples were collected for biochemical analyses. Their testes were dissected out and histological procedure was conducted to perform further histochemical, immunohistochemical analyses and tissue expression analysis by real-time polymerase chain reaction. Expression of the stem cell markers such as c-kit and Thy-1 significantly decreased in the testes of the thyrotoxicosis group compared with the control group; however, Nanog expression was not detected in any of the groups. Similarly, connexin 43 and occludin expressions were also found to be significantly lower in the thyrotoxicosis group. These results on cellular connections are supported with the tissue expression analysis. Our findings are indicative of supporting microenvironmental tissue decay rather than parenchyma damage, which has been actually ignored in the literature. In conclusion, experimental thyrotoxicosis model may have adverse effects on the cell junctional complexes, cell-cell interactions, and pluripotency capacity.

Nephro-protective effect of granulocyte colony-stimulating factor in streptozotocin induced diabetic rats.

Diabetic nephropathy is one of the most serious complications of diabetes and the major cause of end-stage renal failure. Consequences of diabetic nephropathy include increased kidney size and glomerular volume, thickening of basement membranes and progressive accumulation of extracellular matrix. Reports in the literature support an association between increased secretion of inflammatory molecules, such as cytokines, growth factors and metalloproteinases, and development of diabetic nephropathy. We investigated the potential of granulocyte colony- stimulating factor (G-CSF) as a therapeutic candidate for preventing diabetic nephropathy. We used 21 8-week-old male rats; 14 were administered a single dose of 60 mg/kg streptozotocin (STZ) to induce diabetes. The rats were divided into three groups of seven: group 1, control; group 2, diabetic; group 3, diabetic plus G-CSF treatment. After 4 weeks, immunoexpressions of transforming growth factor ß1 (TGF-ß1), Akt and CD34 levels were measured in the kidney tissue. Blood glucose, urine protein and the glomerular area also were measured for each group. We found that G-CSF treatment decreased TGF-ß1 immunoexpression, urine protein and glomerular area in kidneys of diabetic rats, and increased CD 34 and Akt immunoexpression in kidneys of diabetic rats. The effects of G-CSF were independent of blood glucose levels. G-CSF may be a useful therapeutic agent for preventing diabetic nephropathy.

Montelukast prevents ischaemia/reperfusion-induced ovarian damage in rats.

OBJECTIVE: To investigate the efficacy of montelukast for prevention of ischaemia/reperfusion (I/R) injury in rat ovary. STUDY DESIGN: Twenty-four female adult rats were included in the study. I/R injury was induced by CO2 pneumoperitoneum in a laparoscopic rat model. The rats were divided at random into three groups: the sham group was subjected to catheter insertion but was not subjected to pneumoperitoneum; the saline group was subjected to 60 min of pneumoperitoneum and 30 min of reperfusion, with 1 mg/kg physiological saline administered 10 min before pneumoperitoneum; and the montelukast group was subjected to 60 min of pneumoperitoneum and 30 min of reperfusion, with 20mg/kg montelukast administered 10 min before pneumoperitoneum. Damage to ovarian tissue was scored by histopathological evaluation. Caspase-3 expression was determined immunohistochemically. Ovarian tissue levels of malondialdehyde and glutathione, and plasma total antioxidant capacity were measured biochemically. RESULTS: In comparison with the sham group, ovarian sections in the montelukast group had higher scores for follicular degeneration and oedema (p<0.001). Montelukast treatment prevented tissue damage in ovaries, and this result was significant. Caspase-3 expression was only observed in ovarian surface epithelium in the saline and montelukast groups. However, the mean caspase-3 expression score was higher in the saline group than the montelukast group (p<0.001). Tissue levels of malondialdehyde were higher in the montelukast group than the sham group, but plasma total antioxidant capacity and tissue levels of glutathione were significantly lower. Pretreatment with montelukast reduced lipid peroxidation (p<0.005) and improved antioxidant status in rats (p<0.001). CONCLUSION: Montelukast is effective for the prevention of I/R-induced damage in rat ovary.