The role of oxidative and nitrative stress and inflammation in the molecular mechanism of urolithiasis and bladder cancer development

Urolithiasis and bladder cancer are the most common urological diseases worldwide with an unclear aetiology. However, a growing body of evidence suggests the potential role of molecular disturbances of the inflammation as well as oxidative and nitrative stresses, in the pathogenesis of urolithiasis and bladder cancer. Moreover, it may be of particular importance to pay attention to the common pathomechanism of these diseases, as epidemiological reports indicate the occurrence of many similarities, and among them, apart from the high rate of recurrence, risk factors common for urolithiasis and BC, such as male sex or smoking, deserve attention. Therefore, we aimed to detect the potential association between six selected single-nucleotide polymorphisms (-597 A>G (rs1800797) and c.3331 G>A (rs2069845) in IL-6, c.+396 T>G (rs2227307) in IL-8, c.47T > C (p.Val16Ala) (rs4880) in SOD2, c.1823C > T (p.Ser608Leu) (rs2297518) and g.-1026 C>A (rs2779249) in NOS2) and the development of nephrolithiasis and bladder cancer (the TaqMan SNP genotyping assay and real-time PCR were used to genotype profiling). Moreover, we verified the association of urolithiasis or bladder cancer development and mRNA expression of IL-6, IL-8, SOD2, and NOS2 in peripheral blood mononuclear cells (the evaluation of mRNA expression was performed using real-time PCR and 2-ΔCt methods). In addition, data from the structural questionnaire to determine demographic and potential risk factors for urolithiasis and bladder cancer were obtained from patients. Patients and healthy volunteers provided information on their age, lifestyle habits (e.g. the number of fluids consumed daily, including coffee, type of diet), smoking, body mass index (BMI), and co-occurrence disease (e.g. hypertension, diabetes, hypercholesterolaemia). Moreover, the results of blood and urine analyses for each study participant were also studied. Finally, the presented experiments were conducted in cooperation with the Department of Urology of the Provincial Hospital of M. Kacprzak in Płock. In this study, it has been qualified 116 patients diagnosed with BC, 112 with urolithiasis hospitalised at the Department of Urology of the Provincial Hospital of M. Kacprzak in Płock and a homologous group of 114 healthy volunteers based on consent Bioethics Committee of the University of Lodz No. 12/KBBN-UŁ/II/2020-21. The data were obtained for the project, the aim of which was to identify potential prognostic markers of urolithiasis and bladder cancer, indicating at the same time potential common stages in the development mechanisms of the studied diseases.