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

Abstract

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.

Positive Tetrahydrocurcumin-Associated Brain-Related Metabolomic Implications

“…In this direction, Wei et al [47] examined the protective capacity of THC after TBI and found a reduction of oxidative stress caused by brain contusion, reduction of cerebral edema, and reduced death of brain neurons. Different authors observed a curcuminoide-induced reduction in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities as well as a decrease in MDA levels as markers of oxidative stress after TBI, cardiac damage, and bronchopulmonary dysplasia [48][49][50][51][52][53][54]. In addition, Wei et al [47] found an increase in the expression of pro-apoptotic factors in comparison to the expression of anti-apoptotic factors, resulting in Bax-dependent pore formation and increased cell permeability, followed by activation of caspase-3 and degradation of DNA and some critical proteins, ultimately resulting in cell death [19].…”

Quercetin supplementation attenuates airway hyperreactivity and restores airway relaxation in rat pups exposed to hyperoxia

“…Lung inflammation considered to be a risk factor for development of BPD and also contributes to increased, airway hyperresponsiveness in rats. 7,[9][10][11] Although there are many known pathophysiological mechanisms that lead to airway hyperreactivity, treatments for airway hyperreactivity among preterm survivors are surprisingly ineffective. Therefore, a therapy that could prevent neonatal hyperoxia-induced airway hyperreactivity and lung injury is imperative.…”

Oxygen toxicity: cellular mechanisms in normobaric hyperoxia

“…For example, the plant polyphenolic compound curcumin activates Nrf2 indirectly (Park et al 2021 ). Both curcumin (Sakurai et al 2013 ) and its synthetic analogues (Stamenkovska et al 2020 ) reduce lung damage due to hyperoxia in neonatal rats. Similar results have been obtained with resveratrol (Yang et al 2022 ).…”