The role of inducible nitric oxide synthase in urinary bladders of cattle with enzootic hematuria and its struggle with uroplakin III

Changes in uroplakin secretion in the urothelium leads a gradual ability lost in neoplastic conditions. Urothelium is one of the target regions where nitric oxide can damage. Therefore, in this study, the presence of iNOS and UPIII were investigated in bovine enzootic hematuria cases. The results were supported by comparing them with those achieved by critical markers for malignancy of tumor such as caspase 3, Bax, p53, PCNA, and VEGF. The presence of 8-OHDG, a good marker for oxidative DNA damage, was also investigated. For this purpose, urinary bladders with enzootic hematuria were collected from the slaughterhouses. In histopathological examinations, neoplastic, pre-neoplastic, and inflammatory lesions were observed in these urinary bladders. In immunohistochemical examinations, iNOS reacts as negative in the UPIII positive healthy urothelium which preserves the structure of AUM. On the other hand positive reaction has been observed in AUM modified and UPIII negative urothelium. In these cases, as an indicator of oxidative damage, 8-OHdG positivity was observed in the UPIII negative and iNOS positive areas. Additionally, increased cell proliferation, decreased apoptosis as well as p53 disorganization were clearly observed in most of the cases. Thus, the active role of nitric oxide, as a free radical derivative, has been shown in the enzootic hematuria cases of cattle