Investigation of the relationship between ureteropelvic junction obstruction and nitrosative stress

Objective: Ureteropelvic junction obstruction (UPJO) is one of the most common causes of hydronephrosis in the pediatric population. The underlying pathophysiological mechanism is still unknown. In recent studies, it has been shown that nitric oxide (NO) homeostasis is affected in ureteral obstruction. While NO mediates the formation of beneficial physiological effects for the organism, it causes nitrosative stress (NS) with the formation of reactive nitrogen species (RNS), which have cytotoxic effects when produced in excess. Our main aim in this study is to investigate whether there is a relationship between UPJO and nitric oxide radical (NO·), peroxynitrite (ONOO- ), nitric oxide synthase (NOS) activity, which are known as NS markers. Materials and Method: Between October 2022 and June 2023, 50 pediatric patients who were admitted to the pediatric urology outpatient clinic and diagnosed with UPJO and 50 healthy children were included in the study. After detailed anamnesis and physical examination, all patients in the patient group routinely requested biochemistry, whole blood, complete urine analysis, urine culture, urinary system USG, VCUG and scintigraphy, and the results were recorded. Blood serum obtained from all individuals in the patient (group 1) and control (group 2) groups were stored at - 80ºC. After the study and control group patients were completed, the stored serum were studied in the Physiology laboratory of Harran University Faculty of Medicine. Nitric oxide (NO·), peroxynitrite (ONOO-) and nitric oxide synthase (NOS) activity as markers of nitrosative stress were measured spectrophotometrically in serum samples. Student-T test was used to compare patient and control groups, and Pearson Correlation Analysis was used to compare the relationship between parameters. Data are given as mean ± standard deviation or mean (median). Differences between groups were evaluated using the SPSS 25.0 program. Results: Of the 50 patients included in the study (Group 1), 43 were male and 7 were female, with a mean age of 33.00 (80.25) months. Of the 50 patients in the control group (Group 2), 46 were male and 4 were female, with a mean age of 45.00 (71.00) months. The difference between the two groups in terms of age and gender was not statistically significant (p=0.223 and p= 0.525, XI respectively). There was no statistically significant difference between the patient and control groups in terms of NO· and NOS activity (p=0.071 and p=0.926, respectively). Peroxynitrite (ONOO-) level was higher in the patient group than the controls and was statistically significant (p=0.005). Conclusion: There was no strong correlation between NO and NOS and UPJO. However, there was a strong correlation between peroxynitrite, a stronger nitrosative stress marker, and UPJO. The differences between the parameters suggest that, together with the increased nitrosative stress in patients diagnosed with UPJO, compensatory mechanisms may also be activated to maintain NO homeostasis. However, there is a need for multicenter studies with larger series and tissue samples to reveal the effectiveness of this relationship and the possible mechanism. Keywords: Hydronephrosis, nitric oxide, nitric oxide synthase activity, nitrosative stress, peroxynitrite, uretero-pelvic junction obstruction