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Adding glutathione to parenteral nutrition prevents alveolar loss in newborn Guinea pig
Wesam Elremaly1, Ibrahim Mohamed2, Thérèse Rouleau3
1Department of Nutrition, CHU Sainte-Justine, University of Montréal, Montréal, Qc, Canada H3T 1C5.
Insights
Supplementing parenteral nutrition with glutathione (GSSG) protects premature infants
Area of Science:
- Biochemistry
- Neonatal Physiology
- Oxidative Stress Research
Background:
- Bronchopulmonary dysplasia (BPD) is a significant complication of prematurity, linked to alveolar hypoplasia.
- Infants born prematurely have low glutathione levels and receive high oxidative loads, particularly ascorbylperoxide from parenteral nutrition.
- Oxidative stress is a suspected trigger for BPD development.
Purpose of the Study:
- To investigate if adding glutathione (GSSG) to parenteral nutrition can prevent lung damage in newborns.
- To assess the role of ascorbylperoxide as a substrate for glutathione peroxidase.
- To determine if GSSG supplementation mitigates apoptosis and alveolar loss caused by oxidative stress.
Main Methods:
- Ascorbylperoxide's kinetics with glutathione peroxidase were analyzed.
- Guinea pig pups received various parenteral nutrition solutions, including those with and without photo-protection and GSSG supplementation.
- Lung histology and biochemical markers of apoptosis were assessed after 4 days.
Main Results:
- Glutathione peroxidase efficiently detoxifies ascorbylperoxide.
- Parenteral nutrition with high ascorbylperoxide levels induced oxidative stress, apoptosis, and alveolar loss.
- GSSG supplementation in parenteral nutrition prevented these adverse effects.
Conclusions:
- Correcting low glutathione levels in newborns receiving parenteral nutrition protects lungs from ascorbylperoxide toxicity.
- This finding offers a potential strategy for preventing bronchopulmonary dysplasia in premature infants.
- Targeting glutathione levels may be crucial for managing oxidative stress in vulnerable newborns.
Unlabelled:
Bronchopulmonary dysplasia, a main complication of prematurity, is characterized by an alveolar hypoplasia. Oxidative stress is suspected to be a trigger event in this population who has a low level of glutathione, a main endogenous antioxidant, and who receives high oxidative load, particularly ascorbylperoxide from their parenteral nutrition.
Hypothesis:
the addition of glutathione (GSSG) in parenteral nutrition improves detoxification of ascorbylperoxide by glutathione peroxidase and therefore prevents exaggerated apoptosis and loss of alveoli.
Methods:
Ascorbylperoxide is assessed as substrate for glutathione peroxidase in Michaelis-Menten kinetics. Three-days old guinea pig pups were divided in 6 groups to receive, through a catheter in jugular vein, the following solutions: 1) Sham (no infusion); 2) PN(-L): parenteral nutrition protected against light (low ascorbylperoxide); 3) PN(+L): PN without photo-protection (high ascorbylperoxide); 4) 180 μM ascorbylperoxide; 5) PN(+L)+10 μM GSSG; 6) ascorbylperoxyde+10 μM GSSG. After 4 days, lungs were sampled and prepared for histology and biochemical determinations. Data were analysed by ANOVA, p < 0.05 RESULTS: The Km of ascorbylperoxide for glutathione peroxidase was 126 ± 6 μM and Vmax was 38.4 ± 2.5 nmol/min/ U. The presence of GSSG in intravenous solution has prevented the high GSSG, oxidized redox potential of glutathione, activation of caspase-3 (apoptosis marker) and loss of alveoli induced by PN(+L) or ascorbylperoxide.
Conclusion:
A correction of the low glutathione levels observed in newborn animal on parenteral nutrition, protects lungs from toxic effect of ascorbylperoxide. Premature infants having a low level of glutathione, this finding is of high importance because it provides hope in a possible prevention of bronchopulmonary dysplasia.
