ABSTRACT
AIMS: To explore the relationship between oxidative stress biomarkers and the occurrence of acute kidney injury (AKI) alongside notable liver function disturbances in preterm neonates. BACKGROUND: Given the immaturity of kidneys and incomplete liver development in preterm neonates, oxidative stress poses a considerable threat to their renal and hepatic health. OBJECTIVE: To find out the association between various oxidative stress biomarkers and polymorphisms of antioxidant enzymes with renal and live functions. METHODS: In this cross-sectional study, we gathered umbilical cord blood and peripheral blood samples for assessing oxidative stress biomarkers and identifying single nucleotide polymorphisms (SNPs) in antioxidant enzymes. Utilizing enzyme-linked immunosorbent assay kits, we quantified these oxidative stress biomarkers. Receiver-operating characteristics curve analysis was employed to ascertain the predictive capacity of these biomarkers, denoted by the area-under-the-curve (AUC). RESULTS: Our findings revealed that umbilical cord heat-shock proteins emerged as robust predictors of neonatal AKI (AUC: 0.92; 95% CI: 0.8-1) with a defined cut-off concentration of 1.8 ng/mL. Likewise, umbilical cord 8-hydroxy-2-deoxy guanosine demonstrated significant predictability for liver function alterations (AUC: 0.7; 95% CI: 0.6-0.9) at a cut-off concentration of 2487.6 pg/mL. CONCLUSIONS: We observed significant associations between SNPs in endothelial nitric oxide synthase and catalase with both AKI and impaired liver functions. Prospective studies are warranted to validate these findings, with a particular focus on exploring potential antioxidant interventions aimed at mitigating AKI and liver function abnormalities.
ABSTRACT
Background: Preterm neonates, particularly extremely preterm, are susceptible to respiratory distress syndrome (RDS) due to surfactant deficiency. Single nucleotide polymorphisms (SNPs) in the antioxidant enzymes influence the balance between antioxidant and oxidative stress molecules. Objectives: To ascertain the role of SNPs of antioxidant enzymes and oxidative stress biomarkers in preterm neonates with RDS. Design: Observational, cross-sectional study. Methods: Preterm neonates diagnosed with RDS receiving external surfactant within 24 hours were considered as the cases and those without RDS were the control group. Umbilical cord blood and peripheral blood samples before administering surfactant (day 1), and on days 2 and 3 were collected. Plasma malondialdehyde, 8-hydroxy-2-deoxy guanosine (8-OH-dG), advanced oxidation protein products (AOPP), total antioxidant capacity (TAC), visfatin, reduced glutathione, and chaperonin 60 were evaluated using enzyme-linked immunosorbent assay. SNPs in manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPX1 and GPX3), catalase (CAT), glutathione S-transferase (GSTP1) were evaluated using real-time polymerase-chain-reaction. The receiver-operating characteristics curve was used for predicting the accuracy of biomarkers using the area under the curve (AUC) and 95% confidence intervals (95% CI). Results: GSTP1, MnSOD, and eNOS (rs1799983) SNPs were observed to significantly influence the oxidative biomarker concentrations in the entire study population. SNPs in GSTP1, MnSOD, and eNOS (rs1799983) were significantly associated with differences in oxidative stress biomarkers. MnSOD (rs4880) significantly increased the risk of pulmonary complications in neonates with RDS. DNA damage product (8-OH-dG) concentrations before surfactant administration has the best predictive accuracy (AUC: 0.8; 95% CI: 0.7-1; P = .001) for pulmonary complications with a cut-off value of 5008.8 pg/mL. TAC concentrations are significantly greater on day 2 and day 3 amongst neonates receiving surfactant compared to the control group. AOPP in the umbilical cord blood was observed to significantly predict the severity of RDS (AUC: 0.8; 95% CI: 0.6-1; P = .01) with an optimal cut-off value of 88.78 µmol/L. Conclusion: We observed that SNPs in eNOS and MnSOD significantly influence the production of oxidative stress biomarkers in preterm neonates. Baseline 8-OH-dG concentrations best predict the risk of pulmonary complications and AOPP concentrations in the umbilical cord blood predict the risk of RDS severity.