Blunted Reducing Power Generation in Erythrocytes Contributes to Oxidative Stress in Prepubertal Obese Children with Insulin Resistance

Childhood obesity, and specifically its metabolic complications, are related to deficient antioxidant capacity and oxidative stress. Erythrocytes are constantly exposed to multiple sources of oxidative stress; hence, they are equipped with powerful antioxidant mechanisms requiring permanent reducing power generation and turnover. Glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) are two key enzymes on the pentose phosphate pathway. Both enzymes supply reducing power by generating NADPH, which is essential for maintaining the redox balance within the cell and the activity of other antioxidant enzymes. We hypothesized that obese children with insulin resistance would exhibit blunted G6PDH and 6PGDH activities, contributing to their erythrocytes' redox status imbalances. We studied 15 control and 24 obese prepubertal children, 12 of whom were insulin-resistant according to an oral glucose tolerance test (OGTT). We analyzed erythroid malondialdehyde (MDA) and carbonyl group levels as oxidative stress markers. NADP+/NADPH and GSH/GSSG were measured to determine redox status, and NADPH production by both G6PDH and 6PGDH was assayed spectrophotometrically to characterize pentose phosphate pathway activity. Finally, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) activities were also assessed. As expected, MDA and carbonyl groups levels were higher at baseline and along the OGTT in insulin-resistant children. Both redox indicators showed an imbalance in favor of the oxidized forms along the OGTT in the insulin-resistant obese group. Additionally, the NADPH synthesis, as well as GR activity, were decreased. H2O2 removing enzyme activities were depleted at baseline in both obese groups, although after sugar intake only metabolically healthy obese participants were able to maintain their catalase activity. No change was detected in SOD activity between groups. Our results show that obese children with insulin resistance present higher levels of oxidative damage, blunted capacity to generate reducing power, and hampered function of key NADPH-dependent antioxidant enzymes.This research was funded by Spanish Government through the Carlos III Health Institute (Sanitary Research Fund (FIS)), code PI18/01316. A.G.-D. is supported by an intramural grant from the Biomedical Research and Innovation Institute of Cadiz (INiBICA), code LII19/16IN-CO24

Correlation between urinary and serum NT-proBNP in acute bronchiolitis: A pilot study.

We aimed to analyze the correlation of urinary with serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations and its association with severity in acute bronchiolitis. A pilot observational study was conducted between October 1, 2021 and March 31, 2022 including acute bronchiolitis cases who attended our institution. Serum and urinary NT-proBNP concentrations were determined using the Alere i NT-proBNP assay in time-matched urine and blood samples. The Mann-Whitney U test, Spearman's correlations, and simple linear regression were utilized to analyze the association of urine NT-proBNP levels with serum NT-proBNP and with variables indicative of severe bronchiolitis. Seventeen infants (median age 68 [IQR: 36-91] days) with 36 time-matched samples were included. The urine NT-proBNP was positively and strongly correlated with the serum NT-proBNP concentrations (Spearman's ρ = 0.81 & R2  coefficient = 0.751; p  The urinary NT-proBNP concentrations could be a reliable surrogate for serum NT-proBNP levels and resulted elevated in cases of acute bronchiolitis with complicated evolution, suggesting a potential as a noninvasive tool to assess severity in this setting