Serum Oxidative and Nitrosative Stress Markers in Clear Cell Renal Cell Carcinoma

SIMPLE SUMMARY: Oxidative stress, defined as a disturbance in the balance between the production of reactive oxygen species and antioxidant defences, is discussed in relation to its possible role in many pathological conditions, including carcinogenesis. The identification of the oxidative and nitrosative modification of proteins and the definition of their roles in clear cell renal cell carcinoma may be helpful in the elaboration of targeted therapeutic approaches to mitigate protein damage. Therefore, this study aimed to investigate the status of oxidative/nitrosative stress and to explore its role in the development and progression. Oxidative stress increased with the progression of the disease assessed according to the TNM classification and histological grade. Moreover, the presence of angioinvasion in the patients affected the level of nitrite/nitrate, lipid peroxidation and total antioxidant capacity of serum. This is the first report presenting the level of oxidative/nitrosative stress markers among clear cell renal cell carcinoma patients with and without angioinvasion. ABSTRACT: Oxidative stress is believed to be a factor in the development and progression of renal cell carcinoma (RCC). The identification of the oxidative and nitrosative modification of proteins and the definition of their roles in clear cell RCC (ccRCC) may be helpful in the elaboration of targeted therapeutic approaches to mitigate protein damage. This study aimed to investigate the status of oxidative/nitrosative stress and to explore its role in the development and progression. The studied group consisted of 48 newly diagnosed ccRCC and 30 healthy controls. Serum levels of oxidative stress markers—advanced oxidation protein products (AOPP), thiol groups, Amadori reaction products, 3-nitrotyrosine, nitrate/nitrite, malondialdehyde (MDA), 4-hydroxy-2-nonenal and total antioxidant capacity (TAC)—were determined. Additionally, associations between tumour stage assessed according to TNM classification, histological grade, and the effect of the presence of angioinvasion on the level of stress markers were evaluated. The levels of Amadori products, 3-nitrotyrosine, and nitrate/nitrite were elevated, while the levels of thiol groups and TAC decreased in the ccRCC group. The levels of AOPP, Amadori, and 3-nitrotyrosine increased, and thiol groups and TAC levels decreased with the increasing pathological stage of the tumour. In the case of advanced histological assessment of the tumour, we found decreasing levels of thiol groups and increasing levels of MDA. In patients with angioinvasion, nitrate/nitrite and MDA levels were significantly elevated compared to those in patients without angioinvasion. Oxidative stress increased with the progression of the disease assessed according to the TNM and histological grade. These results demonstrate systemic oxidative stress in ccRCC, suggesting the therapeutic application of antioxidants.