Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia

• Published in: Physiological reports Vol. 8; no. 16; pp. e14555 - n/a
• Main Authors: Stamenkovska, Mimoza, Thaçi, Qendrim, Hadzi‐Petrushev, Nikola, Angelovski, Marija, Bogdanov, Jane, Reçica, Shkëlzen, Kryeziu, Islam, Gagov, Hristo, Mitrokhin, Vadim, Kamkin, Andre, Schubert, Rudolf, Mladenov, Mitko, Sopi, Ramadan B.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-08-2020; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Antioxidants; Bioavailability; Bronchial Hyperreactivity - drug therapy; bronchopulmonary dysplasia; Catalase; Catalase - metabolism; Contraction; Curcumin; Curcumin - analogs & derivatives; Curcumin - pharmacology; curcuminoids; Female; Hydrogen peroxide; Hyperoxia; Hyperoxia - drug therapy; Laboratory animals; Lung - metabolism; Lung diseases; Male; Methacholine; Muscle Contraction; Muscle Relaxation; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Neonates; Original Research; Physiology; Rats; Rats, Wistar; Respiratory tract; Respiratory tract diseases; Smooth muscle; Software; Supplements; Trachea - cytology; Trachea - drug effects; Trachea - physiology; tracheal smooth muscle; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; curcuminoids; tracheal smooth muscle; bronchopulmonary dysplasia; catalase
• ISSN: 2051-817X
• DOI: 10.14814/phy2.14555

Background
This study was undertaken to test the hypothesis that the newly synthesized curcuminoids B2BrBC and C66 supplementation will overcome hyperoxia‐induced tracheal hyperreactivity and impairment of relaxation of tracheal smooth muscle (TSM).
Materials and methods
Rat pups (P5) were exposed to hyperoxia (>95% O2) or normoxia for 7 days. At P12, tracheal cylinders were used to study in vitro contractile responses induced by methacholine (10−8–10−4M) or relaxation induced by electrical field stimulation (5–60 V) in the presence/absence of B2BrBC or C66, or to study the direct relaxant effects elicited by both analogs.
Results
Hyperoxia significantly increased contraction and decreased relaxation of TSM compared to normoxia controls. Presence of B2BrBC or C66 normalized both contractile and relaxant responses altered by hyperoxia. Both, curcuminoids directly induced dose‐dependent relaxation of preconstricted TSM. Supplementation of hyperoxic animals with B2BrBC or C66, significantly increased catalase activity. Lung TNF‐α was significantly increased in hyperoxia‐exposed animals. Both curcumin analogs attenuated increases in TNF‐α in hyperoxic animals.
Conclusion
We show that B2BrBC and C66 provide protection against adverse contractility and relaxant effect of hyperoxia on TSM, and whole lung inflammation. Both analogs induced direct relaxation of TSM. Through restoration of catalase activity in hyperoxia, we speculate that analogs are protective against hyperoxia‐induced tracheal hyperreactivity by augmenting H2O2 catabolism. Neonatal hyperoxia induces increased tracheal contractility, attenuates tracheal relaxation, diminishes lung antioxidant capacity, and increases lung inflammation, while monocarbonyl CUR analogs were protective of these adverse effects of hyperoxia. Analogs may be promising new therapies for neonatal hyperoxic airway and lung disease.
This study was undertaken to test the hypothesis that the newly synthesized curcuminoids B2BrBC and C66 supplementation will overcome hyperoxia‐induced airway hyperreactivity and impairment of relaxation of tracheal smooth muscle.