GLUTATHIONE ADDITION TO PARENTERAL NUTRITION PREVENTS PULMONARY OXIDATIVE STRESS AND HYPO-ALVEOLARIZATION IN NEWBORN GUINEA PIG
Bibliographic record
Abstract
Abstract BACKGROUND Parenteral nutrition (PN) is contaminated by peroxides, which induce oxidative stress (oxidized redox potential) and hypoalveolarization in lungs of newborn animals. In human premature newborns, PN is associated to an oxidized redox potential and to a greater prevalence of bronchopulmonary dysplasia (BPD). Peroxides are detoxified by glutathione that is deficient in preterm infants. Hypothesis: Improving glutathione level in premature infants prevents BPD development caused by oxidative stress. OBJECTIVES Assess dose-response effect of glutathione added in PN on alveolarization index and pulmonary redox potential of glutathione (specific oxidative stress marker for peroxides) in newborn guinea pigs. DESIGN/METHODS At day 3 of life, through a jugular catheter, guinea pigs (N=55) received PN (dextrose, amino acids, lipids, vitamins, electrolytes) enriched in glutathione (0, 50, 120, 165, 270, 370, 650 μg GSSG/kg/d). GSSG was used rather than GSH because it has a better stability in PN and similar efficiency in vivo. A control group (no manipulation, fed by mouth) served as reference. After 4 days, lungs were taken for determination of GSH, GSSG, redox potential (capillary electrophoresis) and alveolarization index (AI) (number of intercepts between a 1 mm line and histological structures); higher is AI, higher is the number of alveoli. Data (mean±sem) from animals on PN were compared by ANOVA, p<0.05. RESULTS There was no difference in the alveolarization index between groups receiving doses ranging from 0 to 120 μg/kg/d (25.9 ± 0.6 intercepts/mm) and between those with doses ranging between 165 and 650 μg/kg/d (30.5 ± 0.6 intercepts/mm). However, the difference between the lowest (0–120 μg/kg/d) and the highest doses (165–650 μg/kg/d) was highly significant (p<0.001). The control AI value was 29.4 ± 1.2 intercepts/mm. Increasing GSSG in PN has allowed a significant (r2=0.47; p<0.001) reduction of redox potential, from oxidized status of -205 ± 2 in PN without GSSG to -215 ± 2 mV with the highest dose (650 μg/kg/d); control = -222 ± 3 mV. GSSG in PN was also associated with a decreasing GSSG values (r2=0.49; p<0.001), from 0.84 ± 0.10 in PN without GSSG to 0.38 ± 0.06 nmol/mg prot with the highest dose (650 μg/kg/d); control = 0.35 ± 0.07 nmol/mg prot. There was no effect on GSH (mean value of 29 ± 1 nmol/mg prot). CONCLUSION Addition of glutathione into PN prevents pulmonary oxidative stress. The dose-response curve suggests a specific minimal dose of GSSG to maintain the alveolar integrity. Lower doses were inefficient whereas higher doses are unnecessary, as the index of alveolarization reached a plateau with a mean value similar to that one observed in the control group. This pre-clinical study brings basic data that will serve for the clinical phase I-II study that we are starting soon.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".