May the Nitrosative and Carbonyl Stress Promote Inflammation in Patients with Colorectal Cancer?

Purpose: Overproduction of reactive nitrogen species (RNS) causes the nitrosative stress, which plays a vital role in the development of metabolic, inflammatory, and cancerous diseases. However, the role of nitrosative and carbonyl stress in the biology of colorectal cancer (CRC) is still not well understood. Therefore, this study evaluated nitrosative stress, protein and DNA oxidation/glycoxidation, and pro- and anti-inflammatory cytokines in CRC patients compared with healthy controls.Patients and Methods: Fifty-five CRC patients (21 women, 34 men) and 55 healthy controls matched for sex and age were included in the experiment. Nitrosative stress parameters (nitric oxide (NO), peroxynitrite, S-nitrosothiols, and nitrotyrosine), protein oxidation (total thiols) and glycoxidation products (kynurenine N-formylkynurenine, dityrosine, Amadori products, and amyloid), and DNA damage markers (8-hydroxydeoxyguanosine (8-OHdG)), as well as levels of pro- and anti-inflammatory cytokines, were measured in serum or plasma samples.Results: The levels of NO, peroxynitrite, S-nitrosothiols, nitrotyrosine, total thiols, kynurenine, N-formylkynurenine, dityrosine, Amadori product, amyloid, and 8-OHdG, as well as IL1 alpha, IL113, IL6, IL10, and TNF-alpha, were significantly higher in CRC patients than in controls. Oxidation and glycoxidation products were positively correlated with pro-inflammatory (IL1 alpha, IL113, IL6, TNF alpha) and antiinflammatory cytokines (IL10), indicating that redox damages may promote inflammation in CRC patients. Many redox biomarkers differentiate patients with CRC from healthy individuals with high sensitivity and specificity.Conclusion: Correlations of chosen oxidative products with pro-inflammatory (IL1 alpha, IL113, IL6, TNF alpha) and anti-inflammatory cytokines (IL10) suggest that redox damages may promote inflammation in CRC patients. Thus, our research is the first point for further clinical trials focusing on the evaluation of the diagnostic utility of nitrosative stress biomarkers in a larger group of CRC patients.

Automated summary

The study evaluated the differences in nitrosative stress, protein and DNA oxidation/glycoxidation, as well as pro- and anti-inflammatory cytokines between CRC patients and healthy controls. The results showed that oxidation and glycoxidation products in CRC patients were positively correlated with pro-inflammatory and anti-inflammatory cytokines, indicating that redox damages may promote inflammation in CRC.