Glutathione Redox Activity-An Adaptative Mechanism in Clear Cell Renal Cell Carcinoma

Environmental, genetic, immunological and metabolic factors are involved in renal cell carcinoma development. Clear cell renal carcinoma (ccRCC) is the most frequent renal cancer, with a complex metabolic physiopathology. The present study focuses on the characterization of chemical changes in glutathione redox homeostasis induced by oxidative damage and their relevance to ccRCC. We developed a prospective, case-control study that included 92 subjects diagnosed with ccRCC by histopathological exam and 40 healthy subjects. In each subject, we evaluated the chemical changes in glutathione redox homeostasis, antioxidative capacity, nitrosative stress, carbonyl stress, inflammation (IL-12 family members, albumin), angiogenesis factors and apoptosis. Compared to the control, in ccRCC subjects, we detected high levels of oxidative/electrophile stress, of hypoxia, and of inflammatory- and angiogenesis-related factors and low levels of anti-inflammatory-, anti-oxidative- and apoptosis-related factors. In ccRCC, positive correlations between glutathione redox homeostasis members expression and electrophile metabolites levels, respectively, angiogenesis markers and inflammatory parameters detected. Negative relations with anti-inflammatory and antioxidant markers were assessed. Glutathione redox homeostasis was altered in ccRCC, functioning as an active redox mechanism, with an essential role in the development and progression of ccRCC.