curcumin and Hyperoxia

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).. 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.. 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

Topics: Animals; Bronchial Hyperreactivity; Catalase; Curcumin; Female; Hyperoxia; Lung; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Rats; Rats, Wistar; Trachea; Tumor Necrosis Factor-alpha

To investigate the protective effects and potential mechanism of curcumin on bronchopulmonary dysplasis (BPD) induced by 600 mL/L oxygen in newborn rats.. 108 Sprague-Dawley (SD) specific pathogen-free newborn rats within 6 h after birth were randomly divided into room air group (RA group), 600 mL/L oxygen group (O2 group) and 600 mL/L oxygen + Curcumin group (O2 + Cu group). Eight rats were randomly taken from each group and killed at 4, 7 and 14 d, respectively, after the treatment, and their lung tissues were incised for HE staining. The expressions of IL-6, IL-10 in serum and lung tissue were detected by ELISA; and the protein expression of IGF-I was measured by immunohistochemical method. RESULTS Comparing with the RA group, we found that newborn rats exposed to 600 mL/L oxygen develop a heterogeneous parenchymal lung injury with areas of arrested alveolarization and growth mixed with areas of interstitial thinning, meanwhile, both the expression of IL-6 and IL-10 in serum and lung tissue increased significantly (P < 0.05). However, in O2 + Cu group, IL-6 expression was decreased in different degrees while IL-10 increased significantly (P < 0.05). The highest expression level of IGF-I in RA group were much higher from 4 d to 7 d (alveolar development period) but significantly lower in 14 d. There was a positive correlation between IGF-I and alveolar development. In comparison with RA group, the expression levels of IGF-I in O2 group were significantly lower in 4 d and 7 d but were significantly higher in 14 d (P < 0.05); In comparison with O2 group, the expression levels of IGF-I in O2 group significantly increased in 4 d and 7 d but significantly reduced in 14 d (P < 0.05).. Curcumin may partly prevent the lung injury induced by prolonged hyperoxia exposure in neonatal rats probably via modulating the expressions of IL-6, IL-10 and IGF-I in serum and lung tissue.

Topics: Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Curcumin; Hyperoxia; Insulin-Like Growth Factor I; Interleukin-10; Interleukin-6; Lung; Lung Injury; Oxygen; Rats; Rats, Sprague-Dawley

Curcumin, a potent anti-inflammatory and antioxidant agent, modulates peroxisome proliferator-activated receptor-γ signaling, a key molecule in the etiology of bronchopulmonary dysplasia (BPD). We have previously shown curcumin's acute protection against neonatal hyperoxia-induced lung injury. However, its longer-term protection against BPD is not known. Hypothesizing that concurrent treatment with curcumin protects the developing lung against hyperoxia-induced lung injury long-term, we determined if curcumin protects against hyperoxic neonatal rat lung injury for the first 5 days of life, as determined at postnatal day (PND) 21. One-day-old rat pups were exposed to either 21 or 95% O₂ for 5 days with or without curcumin treatment (5 mg/kg) administered intraperitoneally one time daily, following which the pups grew up to PND21 in room air. At PND21 lung development was determined, including gross and cellular structural and functional effects, and molecular mediators of inflammatory injury. To gain mechanistic insights, embryonic day 19 fetal rat lung fibroblasts were examined for markers of apoptosis and MAP kinase activation following in vitro exposure to hyperoxia for 24 h in the presence or absence of curcumin (5 μM). Curcumin effectively blocked hyperoxia-induced lung injury based on systematic analysis of markers for lung injury (apoptosis, Bcl-2/Bax, collagen III, fibronectin, vimentin, calponin, and elastin-related genes) and lung morphology (radial alveolar count and alveolar septal thickness). Mechanistically, curcumin prevented the hyperoxia-induced increases in cleaved caspase-3 and the phosphorylation of Erk1/2. Molecular effects of curcumin, both structural and cytoprotective, suggest that its actions against hyperoxia-induced lung injury are mediated via Erk1/2 activation and that it is a potential intervention against BPD.

Topics: Animals; Apoptosis; Biomarkers; Cell Proliferation; Curcumin; Elastin; Enzyme Activation; Female; Fibroblasts; Fibronectins; Gene Expression Regulation; Hyperoxia; Lung; MAP Kinase Signaling System; Mesoderm; Protective Agents; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta; Triglycerides

There is no effective intervention to prevent or treat bronchopulmonary dysplasia (BPD). Curcumin has potent antioxidant and anti-inflammatory properties, and it modulates signaling of peroxisome proliferator-activated receptor-γ (PPARγ), an important molecule in the pathobiology of BPD. However, its role in the prevention of BPD is not known. We determined 1) if curcumin enhances neonatal lung maturation, 2) if curcumin protects against hyperoxia-induced neonatal lung injury, and 3) if this protection is mediated by blocking TGF-β. Embryonic day 19 fetal rat lung fibroblasts were exposed to 21% or 95% O(2) for 24 h following 1 h of treatment with curcumin. Curcumin dose dependently accelerated e19 fibroblast differentiation [increased parathyroid hormone-related protein (PTHrP) receptor, PPARγ, and adipocyte differentiation-related protein (ADRP) levels and triolein uptake] and proliferation (increased thymidine incorporation). Pretreatment with curcumin blocked the hyperoxia-induced decrease (PPARγ and ADRP) and increase (α-smooth muscle actin and fibronectin) in markers of lung injury/repair, as well as the activation of TGF-β signaling. In a separate set of experiments, neonatal Sprague-Dawley rat pups were exposed to 21% or 95% O(2) for 7 days with or without intraperitoneal administration of curcumin. Analysis for markers of lung injury/repair [PTHrP receptor, PPARγ, ADRP, fibronectin, TGF-β receptor (activin receptor-like kinase 5), and Smad3] and lung morphology (radial alveolar count) demonstrated that curcumin effectively blocks TGF-β activation and hyperoxia-induced lung injury. Therefore, curcumin accelerates lung maturation by stimulating key alveolar epithelial-mesenchymal interactions and prevents hyperoxia-induced neonatal lung injury, possibly by blocking TGF-β activation, suggesting that it is a potential intervention against BPD.

Topics: Animals; Animals, Newborn; Blotting, Western; Bronchopulmonary Dysplasia; Cell Differentiation; Curcumin; Female; Fibroblasts; Gene Expression Regulation; Humans; Hyperoxia; Infant, Newborn; Infant, Newborn, Diseases; Lung; Parathyroid Hormone-Related Protein; Peroxisome Proliferator-Activated Receptors; PPAR gamma; Pregnancy; Rats; Rats, Sprague-Dawley; Receptor, Parathyroid Hormone, Type 1; Signal Transduction; Transforming Growth Factor beta