Différences liées au sexe dans le métabolisme du glutathion (GSH) du grand prématuré

Abstract

Gender differences in mortality and morbidity are often reported in very preterm infants. In studies aiming to understand the underlying mechanisms, better protection against oxidative stress in baby girls has been suggested. Shortly after birth, we compared glutathione (GSH) metabolism in female and male preterm infants and its relationship with prenatal and postnatal parameters. We took the opportunity of a prospective randomised controlled trial evaluating the safety-efficacy balance of inhaled nitric oxide (Hamon and al., 2005) [12] to assess, in vivo, the antioxidant defences within the first 48 h of life in 240 premature infants less than 32 weeks gestational age (GA). We measured total plasmatic GSH level (nmol/L), intraerythrocyte glutathione peroxidase (GPX, μmol/min/g haemoglobin) and intraerythrocyte glutathione reductase (GR, μmol/min/g haemoglobin) from venous blood samples withdrawn through central lines. Expressed as mean ± standard error of the mean: soon after birth (at 24h median), plasmatic GSH was not different between females (n=123) and males (n=117): 0.932 ± 0.016 vs 0.956 ± 0.012 nmol/L. However, at the same time, GPX, the enzyme involved in GSH synthesis, was at a significantly higher level in baby girls (p<0.001): 11.63 ± 0.25 vs 10.21 ± 0.24 μmol/min/g haemoglobin, as was GR, the enzyme responsible for GSH regeneration (p=0.02): 12.18 ± 0.23 vs 11.22 ± 0.21 μmol/min/g haemoglobin. We observed no significant correlation between GSH levels, GPX, or GR activities with prenatal steroids, GA, birth weight, severity of respiratory disease, and oxygen requirements for the entire population or between the two genders. Whereas the level of glutathione, a key molecule in the defence against oxidative stress in humans, appears to be identical in preterm females and males soon after birth, the enzymes involved in its synthesis (GPX) and regeneration (GR) are higher in females. Study of the sequential progression of GSH, GPX, and GR with regard to prolonged oxidative stress exposure in preterm females and males is needed to better evaluate their potential clinical relevance.