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Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption
Published on: July 30, 2016
[Melatonin modulates the expression of pulmonary prostanoids].
Simón A Aguilar1, Pamela V Arias1, Ignacio Canquil1
1Programa de Fisiopatología, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Melatonin treatment in neonatal lambs exposed to high altitude improved the prostacyclin pathway, a key vasodilator, and reduced cyclooxygenase-2, suggesting reduced oxidative stress and inflammation in pulmonary arterial hypertension of the neonate.
Area of Science:
- Neonatal physiology
- High-altitude medicine
- Pharmacology
Background:
- High-altitude living (above 2,500m) can cause pulmonary arterial hypertension of the neonate (PAHN).
- PAHN is characterized by pulmonary vessel remodeling, abnormal vascular reactivity, and oxidative stress.
- Melatonin may offer antioxidant, anti-remodeling, and vasodilating benefits for PAHN.
Purpose of the Study:
- To investigate the impact of melatonin on prostanoid pathway gene expression in the lungs of neonatal lambs.
- To assess melatonin's effects under conditions simulating high-altitude hypobaric hypoxia.
Main Methods:
- Neonatal lambs were exposed to 3,600m and treated with either melatonin or a vehicle from day 4 to 21.
- Lung tissues were analyzed post-treatment for prostanoid synthase and receptor expression using RT-PCR and Western Blot.
Main Results:
- Melatonin administration upregulated prostacyclin synthase transcript and prostacyclin receptor protein.
- The treatment downregulated both transcript and protein expression of cyclooxygenase-2 (COX-2).
- No significant changes were observed in the expression of the vasoconstrictor thromboxane pathway.
Conclusions:
- Postnatal melatonin treatment enhances the prostacyclin vasodilator pathway in high-altitude exposed lambs.
- Melatonin's reduction of COX-2 suggests potential for decreased oxidative stress and inflammation.
- Melatonin shows promise for managing high-altitude-induced pulmonary hypertension in neonates.
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