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

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435033/
https://www.ncbi.nlm.nih.gov/pubmed/32812392
http://dx.doi.org/10.14814/phy2.14555
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author 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.
author_facet 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.
author_sort Stamenkovska, Mimoza
collection PubMed
description 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% O(2)) or normoxia for 7 days. At P12, tracheal cylinders were used to study in vitro contractile responses induced by methacholine (10(−8)–10(−4)M) 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 H(2)O(2) 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.
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spelling pubmed-74350332020-08-20 Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia 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. Physiol Rep Original Research 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% O(2)) or normoxia for 7 days. At P12, tracheal cylinders were used to study in vitro contractile responses induced by methacholine (10(−8)–10(−4)M) 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 H(2)O(2) 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. John Wiley and Sons Inc. 2020-08-18 /pmc/articles/PMC7435033/ /pubmed/32812392 http://dx.doi.org/10.14814/phy2.14555 Text en © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
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.
Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia
title Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia
title_full Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia
title_fullStr Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia
title_full_unstemmed Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia
title_short Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia
title_sort curcumin analogs (b2brbc and c66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435033/
https://www.ncbi.nlm.nih.gov/pubmed/32812392
http://dx.doi.org/10.14814/phy2.14555
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