Imbalance in the oxygen-transporting properties of erythrocytes and the blood antioxidant system in growth hormone deficient children before therapy and after one year of recombinant growth hormone therapy

Background: Beneficial effects of recombinant growth hormone (rGH) on vascular reactivity and oxidative stress in GH-deficient (GHD) adults have been previously described. However, there is very little information on the state of the blood system or the antioxidant system in children with GHD neither before, not after rGH treatment.

Objective: The aim of our study was to examine the effects of rGH treatment on the oxygen-transporting properties of erythrocytes and the blood antioxidant system in GHD children.

Methods: Eleven treatment-naïve prepubertal children (2 girls, 9 boys; aged 4 to 9 years; mean age 6.1 ± 2.2 years) with GHD were included in the study. The morphology and oxygen-transporting properties of erythrocytes were examined and compared to a control group of 9 healthy prepubertal children (2 girls and 7 boys; aged 5 to 7 years; mean CA 5.9 ± 0.9 years). Further, the state of the antioxidant system of the blood (i.e., superoxide dismutase [SOD] activity, catalase activity, ceruloplasmin levels, and total antioxidant capacity [TAC] of plasma, glutathione levels) was evaluated and was compared against a control group of 9 girls with Turner syndrome (aged 10 to 14 years; mean CA 12.8 ± 0.9 years) as a suitable model of a growth deficient child with no growth hormone deficiency.

Results: The morphological structure of erythrocytes in GHD children is altered as is the cells' functional abilities to transport and release oxygen and the saturation of Hb with oxygen: a 23% higher binding ability and a 28% higher resetting ability, increased levels of oxyhaemoglobin (oxy-Hb) by 54% and NO-haemoglobin (NO-Hb) by 50%. The antioxidant system substantially compromised with 40% lower TAC and a 30% lower reduced glutathione levels. After treatment, the morphofunctional parameters of erythrocytes were reduced to normal, but the antioxidant status parameters remained on a low level.

Conclusions: Our study indicates that children with GHD have an imbalance in their oxygen-transporting system, experience mild oxidative stress development and the presence of tissue hypoxia. GH therapy in these children results in a partial correction to these negative conditions. This study suggests a possible interaction between the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis and the morphofunctional properties of erythrocytes and indicates the development of adaptive mechanisms in GHD children to ensure adequate oxygen supply.

Keywords: growth hormone deficiency, blood antioxidant system, oxygen transport, erythrocytes, Raman spectroscopy