ASSESSMENT OF NITRIC OXIDE METABOLISM, MALONDIALDEHYDE, SIALIC ACIDS , AND ENOS GENE VARIANTS (RS1799983) IN NEWBORNS WITH HYPOXIC-ISCHEMIC ENCEPHALOPATHY FOLLOWING L-CARNITINE ADMINISTRATION

Abstract

In Ukraine, conditions arising during the perinatal period accounted for 57.9% of infant mortality under 1 year of age in 2021, compared to 55.6% in 2017. Hypoxic-ischemic encephalopathy (HIE) remains a leading cause of neurological complications and disability, particularly in low-income countries, where its incidence reaches 10-20 cases per 1,000 newborns. Despite advances in medical care, the risk of irreversible brain damage from HIE remains high. The processes associated with HIE are marked by oxidative stress and disrupted ionic homeostasis, leading to neuroapoptosis and necrosis of brain cells. Objective: to investigate metabolic changes in newborns with HIE by assessing nitric oxide, malondialdehyde, sialic acids, eNOS gene variants, and the impact of L-carnitine on metabolite concentrations. Materials and Methods. The study included 30 neonates. The main group consisted of 16 children with HIE, monitored in an outpatient follow-up clinic and receiving levocarnitine. The comparison group included 14 randomly selected relatively healthy neonates without HIE. Levels of nitrites, nitrates, malondialdehyde, and sialic acids in urine were assessed during the early neonatal period and at 6-9 months of age in children with HIE. In the comparison group, metabolite levels were measured at 6-9 months of age. Results. The study revealed increased nitrite (1.71 vs. 2.7; p=0.003) and nitrate (3.72 vs. 5.42; p=0.010) levels in newborns with HIE, indicating activation of nitric oxide metabolism. Malondialdehyde levels decreased following L-carnitine treatment, suggesting reduced oxidative stress. Genetic analysis showed a higher frequency of the 894GT genotype in the eNOS gene among newborns with reduced sialic acid concentrations (0.2 vs. 0.59; p=0.008). Conclusion. L-carnitine shows potential neuroprotective effects in the treatment of HIE by stabilizing mitochondrial function and reducing oxidative stress. Further studies are needed to optimize therapeutic strategies.