The aim of these studies was to examine the nephroprotective effect of melatonin following the anthracycline administration [daunorubicin (DNR); doxorubicin (DOX)] in rats. Application of these drugs in chemotherapy is limited because of their cardiotoxicity and nephrotoxicity. Rats of the Buffalo strain were divided into groups according to the cytostatic drug used, its dose and sequence of administration [DNR or DOX single (i.v.) dose of 10 mg/kg b.w., i.e. acute intoxication and 3 mg/kg b.w. (i.v.) weekly for 3 wk, subchronic intoxication]. Melatonin was administered subcutaneously before and after every injection of a cytostatic drug at a dose of 10 mg/kg b.w. The severity of renal alterations was examined both biochemically [levels of lipid peroxidation markers, malonyldialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)], or histologically. A statistically significant decrease in renal damage was noted after melatonin administration to acutely or subchronically intoxicated DNR-treated and DOX-treated rats. Biochemical assays revealed significant decreases in MDA and 4-HDA levels following application of melatonin during subchronic DNR or DOX intoxication. In summary, melatonin was found to exert a protective effect on the kidney, which was particularly evident after subchronic DOX and DNR intoxication, using both histological or biochemical methods.
10621 Background: Vascular endothelial growth factor (VEGF) is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis. This cytokine selectively induces cells proliferation and migration, increases permeability of microvessels and activates proteolitic enzymes involved in tumor invasiveness. C-met is tyrosine kinase receptor; its activation can increase tumorigenicity, induce cell motility and enhance invasiveness and metastasis. This protein can increase production of protease and urokinase which are associated with membrane degradation crucial for metastasis. The relationships between both cytokines are not clearly identified. In this study, we evaluated VEGF and c-met expression in homogenous group of 99 patients with stage II ductal breast carcinomas and analyzed correlations between both markers. Methods: Microscopic studies were performed on formalin-fixed, paraffin-embedded cancer tissues, obtained during surgery and stained routinely with haematoxylin and eosin. Expression of VEGF and c-met was evaluated using a standard immunoperoxidase technique and area with molecule expression, intensity of color reaction and product of both findings were counted. Association between markers expressions was tested by Spearman Correlation Coefficient. Results: Expression of c-met was found in 37 (37.37%) breast tumors, while expression of VEGF was observed in 67 (67.67%) cases. There were strong correlations between expressions of both cytokines. The relationships were found between area with molecules’ expression (p = 0.0438) and intensity of reaction (p = 0.0461), also in the product of both findings (p = 0.0229). Conclusions: The results of our study confirms hypothesis that c-met may act as an indirect angiogenic factor by inducing expression of VEGF. No significant financial relationships to disclose.
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