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

Justyna Dorf; Konrad Zaręba; Joanna Matowicka-Karna; Anna Pryczynicz; Katarzyna Guzińska-Ustymowicz; Anna Zalewska; Mateusz Maciejczyk

doi:10.2147/JIR.S374387

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

J Inflamm Res. 2022 Aug 11:15:4585-4600. doi: 10.2147/JIR.S374387. eCollection 2022.

Authors

Justyna Dorf¹, Konrad Zaręba², Joanna Matowicka-Karna¹, Anna Pryczynicz³, Katarzyna Guzińska-Ustymowicz³, Anna Zalewska⁴, Mateusz Maciejczyk⁵

Affiliations

¹ Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Bialystok, Poland.
² 2nd Clinical Department of General and Gastroenterological Surgery, Medical University of Bialystok, Bialystok, Poland.
³ Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
⁴ Independent Laboratory of Experimental Dentistry, Medical University of Bialystok, Bialystok, Poland.
⁵ Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, Poland.

Abstract

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 IL1α, IL1β, IL6, IL10, and TNF-α, were significantly higher in CRC patients than in controls. Oxidation and glycoxidation products were positively correlated with pro-inflammatory (IL1α, IL1β, IL6, TNFα) and anti-inflammatory 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 (IL1α, IL1β, IL6, TNFα) 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.

Keywords: colorectal cancer; cytokines; inflammation; nitrosative stress.

Grants and funding

This work was granted by the Medical University of Bialystok, Poland (grant numbers: SUB/1/DN/19/001/2209/20; SUB/1/DN/20/005/2209). Dr Mateusz Maciejczyk was supported by the Foundation for Polish Science (FNP).