Adelmidrol: A New Promising Antioxidant and Anti-Inflammatory Therapeutic Tool in Pulmonary Fibrosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Induction of Lung Injury
2.3. Experimental Groups
- Bleomycin + vehicle group. Mice received bleomycin administration and were treated daily with the vehicle (saline);
- Bleomycin + adelmidrol group. Mice received bleomycin administration and were treated daily with adelmidrol (10 mg/Kg);
- Sham + vehicle group. Identical to the bleomycin + vehicle group, but animals received intratracheal instillation of saline (0.9% w/v) instead of bleomycin, and were treated daily with the vehicle (saline);
- Sham + adelmidrol group. Identical to the bleomycin + adelmidrol group, but animals received intratracheal instillation of saline (0.9% w/v) instead of bleomycin, and were treated daily with adelmidrol (10 mg/Kg).
2.4. Survival Rate and Body Weight Gain
2.5. Bronchoalveolar Lavage (BAL)
2.6. Measurement of Lung Edema
2.7. Histological Examination
2.8. Measurement of Chymase Activity
2.9. MPO Assay
2.10. Soluble Collagen Assay
2.11. Enzyme-Linked Immunosorbent Assays (ELISA)
2.12. Nitric Oxide (NO) Analysis
2.13. Measurement of Oxidative Stress
2.14. Western Blot Analysis
2.15. Materials
2.16. Statistical Evaluation
3. Results
3.1. Adelmidrol Exerts Anti-Inflammatory Effects in a Pulmonary Fibrosis Model
3.2. Adelmidrol Modulates the Lung Production of IL6, TNF-α, and IL-1β and Oxidative Stress Induced by Pulmonary Fibrosis
3.3. Adelmidrol Manages the STAT3 and NF-kB Pathway
3.4. Adelmidrol Reduced the Mortality Rate and Improved the Histopathological Score
3.5. Adelmidrol Reduced Mast Cell Degranulation and Lung Fibrotic Changes
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- King, T.E., Jr.; Pardo, A.; Selman, M. Idiopathic pulmonary fibrosis. Lancet 2011, 378, 1949–1961. [Google Scholar] [CrossRef]
- Datta, A.; Scotton, C.J.; Chambers, R.C. Novel therapeutic approaches for pulmonary fibrosis. Br. J. Pharmacol. 2011, 163, 141–172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Usuki, J.; Fukuda, Y. Evolution of three patterns of intra-alveolar fibrosis produced by bleomycin in rats. Pathol. Int. 1995, 45, 552–564. [Google Scholar] [CrossRef] [PubMed]
- Shi, K.; Jiang, J.; Ma, T.; Xie, J.; Duan, L.; Chen, R.; Song, P.; Yu, Z.; Liu, C.; Zhu, Q.; et al. Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung injury model in mice. Respir. Physiol. Neurobiol. 2014, 190, 113–117. [Google Scholar] [CrossRef] [PubMed]
- Chaudhary, N.I.; Schnapp, A.; Park, J.E. Pharmacologic differentiation of inflammation and fibrosis in the rat bleomycin model. Am. J. Respir. Crit. Care Med. 2006, 173, 769–776. [Google Scholar] [CrossRef] [PubMed]
- Moeller, A.; Ask, K.; Warburton, D.; Gauldie, J.; Kolb, M. The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int. J. Biochem. Cell Biol. 2008, 40, 362–382. [Google Scholar] [CrossRef] [Green Version]
- Schmid, H.H.; Berdyshev, E.V. Cannabinoid receptor-inactive N-acylethanolamines and other fatty acid amides: Metabolism and function. Prostaglandins Leukot. Essent. Fatty Acids 2002, 66, 363–376. [Google Scholar] [CrossRef]
- Di Paola, R.; Impellizzeri, D.; Fusco, R.; Cordaro, M.; Siracusa, R.; Crupi, R.; Esposito, E.; Cuzzocrea, S. Ultramicronized palmitoylethanolamide (PEA-um((R))) in the treatment of idiopathic pulmonary fibrosis. Pharmacol. Res. 2016, 111, 405–412. [Google Scholar] [CrossRef]
- Fusco, R.; Gugliandolo, E.; Campolo, M.; Evangelista, M.; Di Paola, R.; Cuzzocrea, S. Effect of a new formulation of micronized and ultramicronized N-palmitoylethanolamine in a tibia fracture mouse model of complex regional pain syndrome. PLoS ONE 2017, 12, e0178553. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Di Paola, R.; Cordaro, M.; Crupi, R.; Siracusa, R.; Campolo, M.; Bruschetta, G.; Fusco, R.; Pugliatti, P.; Esposito, E.; Cuzzocrea, S. Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO. Shock 2016, 46, 202–213. [Google Scholar] [CrossRef]
- Impellizzeri, D.; Peritore, A.F.; Cordaro, M.; Gugliandolo, E.; Siracusa, R.; Crupi, R.; D’Amico, R.; Fusco, R.; Evangelista, M.; Cuzzocrea, S.; et al. The neuroprotective effects of micronized PEA (PEA-m) formulation on diabetic peripheral neuropathy in mice. FASEB J. 2019, 33, 11364–11380. [Google Scholar] [CrossRef] [PubMed]
- Cordaro, M.; Impellizzeri, D.; Bruschetta, G.; Siracusa, R.; Crupi, R.; Di Paola, R.; Esposito, E.; Cuzzocrea, S. A novel protective formulation of Palmitoylethanolamide in experimental model of contrast agent induced nephropathy. Toxicol. Lett. 2016, 240, 10–21. [Google Scholar] [CrossRef] [PubMed]
- Impellizzeri, D.; Bruschetta, G.; Cordaro, M.; Crupi, R.; Siracusa, R.; Esposito, E.; Cuzzocrea, S. Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain. J. Neuroinflamm. 2014, 11, 136. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Petrosino, S.; Puigdemont, A.; Della Valle, M.F.; Fusco, M.; Verde, R.; Allara, M.; Aveta, T.; Orlando, P.; Di Marzo, V. Adelmidrol increases the endogenous concentrations of palmitoylethanolamide in canine keratinocytes and down-regulates an inflammatory reaction in an in vitro model of contact allergic dermatitis. Vet. J. 2016, 207, 85–91. [Google Scholar] [CrossRef] [PubMed]
- Ostardo, E.; Impellizzeri, D.; Cervigni, M.; Porru, D.; Sommariva, M.; Cordaro, M.; Siracusa, R.; Fusco, R.; Gugliandolo, E.; Crupi, R.; et al. Urology Study, G. Adelmidrol + sodium hyaluronate in IC/BPS or conditions associated to chronic urothelial inflammation. A translational study. Pharmacol. Res. 2018, 134, 16–30. [Google Scholar] [CrossRef] [PubMed]
- De Filippis, D.; D’Amico, A.; Cinelli, M.P.; Esposito, G.; Di Marzo, V.; Iuvone, T. Adelmidrol, a palmitoylethanolamide analogue, reduces chronic inflammation in a carrageenin-granuloma model in rats. J. Cell Mol. Med. 2009, 13, 1086–1095. [Google Scholar] [CrossRef] [PubMed]
- Di Paola, R.; Fusco, R.; Impellizzeri, D.; Cordaro, M.; Britti, D.; Morittu, V.M.; Evangelista, M.; Cuzzocrea, S. Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats. Arthritis Res. Ther. 2016, 18, 291. [Google Scholar] [CrossRef] [Green Version]
- Cordaro, M.; Impellizzeri, D.; Gugliandolo, E.; Siracusa, R.; Crupi, R.; Esposito, E.; Cuzzocrea, S. Adelmidrol, a Palmitoylethanolamide Analogue, as a New Pharmacological Treatment for the Management of Inflammatory Bowel Disease. Mol. Pharmacol. 2016, 90, 549–561. [Google Scholar] [CrossRef] [Green Version]
- Genovese, T.; Esposito, E.; Mazzon, E.; Di Paola, R.; Meli, R.; Bramanti, P.; Piomelli, D.; Calignano, A.; Cuzzocrea, S. Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury. J. Pharmacol. Exp. Ther. 2008, 326, 12–23. [Google Scholar] [CrossRef]
- Impellizzeri, D.; Talero, E.; Siracusa, R.; Alcaide, A.; Cordaro, M.; Maria Zubelia, J.; Bruschetta, G.; Crupi, R.; Esposito, E.; Cuzzocrea, S.; et al. Protective effect of polyphenols in an inflammatory process associated with experimental pulmonary fibrosis in mice. Br. J. Nutr. 2015, 114, 853–865. [Google Scholar] [CrossRef]
- Saadat, S.; Beheshti, F.; Askari, V.R.; Hosseini, M.; Mohamadian Roshan, N.; Boskabady, M.H. Aminoguanidine affects systemic and lung inflammation induced by lipopolysaccharide in rats. Respir. Res. 2019, 20, 96. [Google Scholar] [CrossRef] [PubMed]
- Shimbori, C.; Upagupta, C.; Bellaye, P.-S.; Ayaub, E.A.; Sato, S.; Yanagihara, T.; Zhou, Q.; Ognjanovic, A.; Ask, K.; Gauldie, J. Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis. Thorax 2019, 74, 455–465. [Google Scholar] [CrossRef] [PubMed]
- Zhang, C.; Zhang, L.H.; Wu, Y.F.; Lai, T.W.; Wang, H.S.; Xiao, H.; Che, L.Q.; Ying, S.M.; Li, W.; Chen, Z.H.; et al. Suhuang antitussive capsule at lower doses attenuates airway hyperresponsiveness, inflammation, and remodeling in a murine model of chronic asthma. Sci. Rep. 2016, 6, 21515. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pasztor, M.; Fischer, J.; Nagy, Z.; Sohar, I. Proteolytic enzyme activities in rat peritoneal exudate. Acta Biol. Hung. 1991, 42, 285–295. [Google Scholar] [PubMed]
- Tomimori, Y.; Muto, T.; Saito, K.; Tanaka, T.; Maruoka, H.; Sumida, M.; Fukami, H.; Fukuda, Y. Involvement of mast cell chymase in bleomycin-induced pulmonary fibrosis in mice. Eur. J. Pharmacol. 2003, 478, 179–185. [Google Scholar] [CrossRef] [PubMed]
- Mullane, K.M.; Kraemer, R.; Smith, B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J. Pharmacol. Methods 1985, 14, 157–167. [Google Scholar] [CrossRef]
- Conte, E.; Fagone, E.; Gili, E.; Fruciano, M.; Iemmolo, M.; Pistorio, M.P.; Impellizzeri, D.; Cordaro, M.; Cuzzocrea, S.; Vancheri, C. Preventive and therapeutic effects of thymosin beta4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis. Oncotarget 2016, 7, 33841–33854. [Google Scholar] [CrossRef]
- Zhang, J.; Cui, R.; Feng, Y.; Gao, W.; Bi, J.; Li, Z.; Liu, C. Serotonin Exhibits Accelerated Bleomycin-Induced Pulmonary Fibrosis through TPH1 Knockout Mouse Experiments. Mediators Inflamm. 2018, 2018, 7967868. [Google Scholar] [CrossRef]
- Yasui, H.; Gabazza, E.C.; Tamaki, S.; Kobayashi, T.; Hataji, O.; Yuda, H.; Shimizu, S.; Suzuki, K.; Adachi, Y.; Taguchi, O. Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse. Am. J. Resp. Crit. Care 2001, 163, 1660–1668. [Google Scholar] [CrossRef]
- Atzori, L.; Chua, F.; Dunsmore, S.; Willis, D.; Barbarisi, M.; McAnulty, R.; Laurent, G. Attenuation of bleomycin induced pulmonary fibrosis in mice using the heme oxygenase inhibitor Zn-deuteroporphyrin IX-2, 4-bisethylene glycol. Thorax 2004, 59, 217–223. [Google Scholar] [CrossRef] [Green Version]
- Liu, M.H.; Lin, A.H.; Ko, H.K.; Perng, D.W.; Lee, T.S.; Kou, Y.R. Prevention of Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Mice by Paeonol. Front. Physiol. 2017, 8, 193. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Luzina, I.G.; Lockatell, V.; Todd, N.W.; Kopach, P.; Pentikis, H.S.; Atamas, S.P. Pharmacological In Vivo Inhibition of S-Nitrosoglutathione Reductase Attenuates Bleomycin-Induced Inflammation and Fibrosis. J. Pharmacol. Exp. Ther. 2015, 355, 13–22. [Google Scholar] [CrossRef] [Green Version]
- Liu, L.; Lu, W.; Ma, Z.; Li, Z. Oxymatrine attenuates bleomycin-induced pulmonary fibrosis in mice via the inhibition of inducible nitric oxide synthase expression and the TGF-β/Smad signaling pathway. Int. J. Mol. Med. 2012, 29, 815–822. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 1979, 95, 351–358. [Google Scholar] [CrossRef]
- Gugliandolo, E.; Fusco, R.; Biundo, F.; D’Amico, R.; Benedetto, F.; Di Paola, R.; Cuzzocrea, S. Palmitoylethanolamide and Polydatin combination reduces inflammation and oxidative stress in vascular injury. Pharmacol. Res. 2017, 123, 83–92. [Google Scholar] [CrossRef]
- Aloe, L.; Leon, A.; Levi-Montalcini, R. A proposed autacoid mechanism controlling mastocyte behaviour. Agents Actions 1993, 39, C145–C147. [Google Scholar] [CrossRef]
- Costa, B.; Comelli, F.; Bettoni, I.; Colleoni, M.; Giagnoni, G. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: Involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. Pain 2008, 139, 541–550. [Google Scholar] [CrossRef] [PubMed]
- De Filippis, D.; Luongo, L.; Cipriano, M.; Palazzo, E.; Cinelli, M.P.; de Novellis, V.; Maione, S.; Iuvone, T. Palmitoylethanolamide reduces granuloma-induced hyperalgesia by modulation of mast cell activation in rats. Mol. Pain 2011, 7, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Esposito, E.; Paterniti, I.; Mazzon, E.; Genovese, T.; Di Paola, R.; Galuppo, M.; Cuzzocrea, S. Effects of palmitoylethanolamide on release of mast cell peptidases and neurotrophic factors after spinal cord injury. Brain Behav. Immun. 2011, 25, 1099–1112. [Google Scholar] [CrossRef]
- Janick-Buckner, D.; Ranges, G.E.; Hacker, M.P. Alteration of bronchoalveolar lavage cell populations following bleomycin treatment in mice. Toxicol. Appl. Pharmacol. 1989, 100, 465–473. [Google Scholar] [CrossRef]
- Toews, G.B. Cytokines and the lung. Eur. Respir. J. Suppl. 2001, 34, 3s–17s. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Coward, W.R.; Saini, G.; Jenkins, G. The pathogenesis of idiopathic pulmonary fibrosis. Ther. Adv. Respir. Dis. 2010, 4, 367–388. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hay, J.; Shahzeidi, S.; Laurent, G. Mechanisms of bleomycin-induced lung damage. Arch. Toxicol. 1991, 65, 81–94. [Google Scholar] [CrossRef]
- Day, B.J. Antioxidants as potential therapeutics for lung fibrosis. Antioxid. Redox Signal. 2008, 10, 355–370. [Google Scholar] [CrossRef] [Green Version]
- Gao, F.; Kinnula, V.L.; Myllarniemi, M.; Oury, T.D. Extracellular superoxide dismutase in pulmonary fibrosis. Antioxid. Redox Signal. 2008, 10, 343–354. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hagen, T.M.; Brown, L.A.; Jones, D.P. Protection against paraquat-induced injury by exogenous GSH in pulmonary alveolar type II cells. Biochem. Pharmacol. 1986, 35, 4537–4542. [Google Scholar] [CrossRef]
- Galm, U.; Hager, M.H.; Van Lanen, S.G.; Ju, J.; Thorson, J.S.; Shen, B. Antitumor antibiotics: Bleomycin, enediynes, and mitomycin. Chem. Rev. 2005, 105, 739–758. [Google Scholar] [CrossRef] [PubMed]
- Cheresh, P.; Kim, S.J.; Tulasiram, S.; Kamp, D.W. Oxidative stress and pulmonary fibrosis. Biochim. Biophys. Acta 2013, 1832, 1028–1040. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Galuppo, M.; Di Paola, R.; Mazzon, E.; Esposito, E.; Paterniti, I.; Kapoor, A.; Thiemermann, C.; Cuzzocrea, S. GW0742, a high affinity PPAR-beta/delta agonist reduces lung inflammation induced by bleomycin instillation in mice. Int. J. Immunopathol. Pharmacol. 2010, 23, 1033–1046. [Google Scholar] [CrossRef] [PubMed]
- Di Paola, R.; Talero, E.; Galuppo, M.; Mazzon, E.; Bramanti, P.; Motilva, V.; Cuzzocrea, S. Adrenomedullin in inflammatory process associated with experimental pulmonary fibrosis. Respir. Res. 2011, 12, 41. [Google Scholar] [CrossRef] [Green Version]
- Galuppo, M.; Esposito, E.; Mazzon, E.; Di Paola, R.; Paterniti, I.; Impellizzeri, D.; Cuzzocrea, S. MEK inhibition suppresses the development of lung fibrosis in the bleomycin model. Naunyn Schmiedebergs Arch. Pharmacol 2011, 384, 21–37. [Google Scholar] [CrossRef] [PubMed]
- Lakari, E.; Soini, Y.; Saily, M.; Koistinen, P.; Paakko, P.; Kinnula, V.L. Inducible nitric oxide synthase, but not xanthine oxidase, is highly expressed in interstitial pneumonias and granulomatous diseases of human lung. Am. J. Clin. Pathol. 2002, 117, 132–142. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Valentino, L.; Pierre, J. JAK/STAT signal transduction: Regulators and implication in hematological malignancies. Biochem. Pharmacol. 2006, 71, 713–721. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Dees, C.; Beyer, C.; Lin, N.Y.; Distler, A.; Zerr, P.; Palumbo, K.; Susok, L.; Kreuter, A.; Distler, O.; et al. Inhibition of casein kinase II reduces TGFbeta induced fibroblast activation and ameliorates experimental fibrosis. Ann. Rheum. Dis. 2015, 74, 936–943. [Google Scholar] [CrossRef]
- Tian, B.; Patrikeev, I.; Ochoa, L.; Vargas, G.; Belanger, K.K.; Litvinov, J.; Boldogh, I.; Ameredes, B.T.; Motamedi, M.; Brasier, A.R. NF-κB mediates mesenchymal transition, remodeling, and pulmonary fibrosis in response to chronic inflammation by viral RNA patterns. Am. J. Resp. Cell Mol. 2017, 56, 506–520. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bowie, A.; O’Neill, L.A. Oxidative stress and nuclear factor-kappaB activation: A reassessment of the evidence in the light of recent discoveries. Biochem. Pharmacol. 2000, 59, 13–23. [Google Scholar] [CrossRef]
- Selman, M.; King, T.E.; Pardo, A.; American Thoracic, S.; European Respiratory, S.; American College of Chest, P. Idiopathic pulmonary fibrosis: Prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann. Intern. Med. 2001, 134, 136–151. [Google Scholar] [CrossRef]
- Moon, T.C.; St Laurent, C.D.; Morris, K.E.; Marcet, C.; Yoshimura, T.; Sekar, Y.; Befus, A.D. Advances in mast cell biology: New understanding of heterogeneity and function. Mucosal. Immunol. 2010, 3, 111–128. [Google Scholar] [CrossRef] [Green Version]
- Inoue, Y.; King, T.E., Jr.; Tinkle, S.S.; Dockstader, K.; Newman, L.S. Human mast cell basic fibroblast growth factor in pulmonary fibrotic disorders. Am. J. Pathol. 1996, 149, 2037–2054. [Google Scholar]
- Kawanami, O.; Ferrans, V.J.; Fulmer, J.D.; Crystal, R.G. Ultrastructure of pulmonary mast cells in patients with fibrotic lung disorders. Lab. Investig. 1979, 40, 717–734. [Google Scholar]
- Cha, S.I.; Chang, C.S.; Kim, E.K.; Lee, J.W.; Matthay, M.A.; Golden, J.A.; Elicker, B.M.; Jones, K.; Collard, H.R.; Wolters, P.J. Lung mast cell density defines a subpopulation of patients with idiopathic pulmonary fibrosis. Histopathology 2012, 61, 98–106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Andersson, C.K.; Andersson-Sjoland, A.; Mori, M.; Hallgren, O.; Pardo, A.; Eriksson, L.; Bjermer, L.; Lofdahl, C.G.; Selman, M.; Westergren-Thorsson, G.; et al. Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis. Respir. Res. 2011, 12, 139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Edwards, S.T.; Cruz, A.C.; Donnelly, S.; Dazin, P.F.; Schulman, E.S.; Jones, K.D.; Wolters, P.J.; Hoopes, C.; Dolganov, G.M.; Fang, K.C. c-Kit immunophenotyping and metalloproteinase expression profiles of mast cells in interstitial lung diseases. J. Pathol. 2005, 206, 279–290. [Google Scholar] [CrossRef] [PubMed]
- Overed-Sayer, C.; Rapley, L.; Mustelin, T.; Clarke, D.L. Are mast cells instrumental for fibrotic diseases? Front. Pharmacol. 2013, 4, 174. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, X.Y.; Zhao, L.Y.; Zheng, Q.S.; Su, J.L.; Guan, H.; Shang, F.J.; Niu, X.L.; He, Y.P.; Lu, X.L. Chymase induces profibrotic response via transforming growth factor-beta 1/Smad activation in rat cardiac fibroblasts. Mol. Cell Biochem. 2008, 310, 159–166. [Google Scholar] [CrossRef] [PubMed]
- Lindstedt, K.A.; Wang, Y.; Shiota, N.; Saarinen, J.; Hyytiainen, M.; Kokkonen, J.O.; Keski-Oja, J.; Kovanen, P.T. Activation of paracrine TGF-beta1 signaling upon stimulation and degranulation of rat serosal mast cells: A novel function for chymase. FASEB J. 2001, 15, 1377–1388. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fernandez, I.E.; Eickelberg, O. The impact of TGF-β on lung fibrosis: From targeting to biomarkers. Proc. Am. Thorac. Soc. 2012, 9, 111–116. [Google Scholar] [CrossRef]
- Sime, P.J.; Xing, Z.; Graham, F.L.; Csaky, K.G.; Gauldie, J. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J. Clin. Investig. 1997, 100, 768. [Google Scholar] [CrossRef] [Green Version]
- Tanaka, K.-I.; Ishihara, T.; Azuma, A.; Kudoh, S.; Ebina, M.; Nukiwa, T.; Sugiyama, Y.; Tasaka, Y.; Namba, T.; Ishihara, T. Therapeutic effect of lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 2010, 298, L348–L360. [Google Scholar] [CrossRef]
- Sims, J.E.; Smith, D.E. The IL-1 family: Regulators of immunity. Nat. Rev. Immunol. 2010, 10, 89–102. [Google Scholar] [CrossRef]
- Tatler, A.L.; Jenkins, G. TGF-beta activation and lung fibrosis. Proc. Am. Thorac. Soc. 2012, 9, 130–136. [Google Scholar] [CrossRef] [PubMed]
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Fusco, R.; Cordaro, M.; Genovese, T.; Impellizzeri, D.; Siracusa, R.; Gugliandolo, E.; Peritore, A.F.; D’Amico, R.; Crupi, R.; Cuzzocrea, S.; et al. Adelmidrol: A New Promising Antioxidant and Anti-Inflammatory Therapeutic Tool in Pulmonary Fibrosis. Antioxidants 2020, 9, 601. https://doi.org/10.3390/antiox9070601
Fusco R, Cordaro M, Genovese T, Impellizzeri D, Siracusa R, Gugliandolo E, Peritore AF, D’Amico R, Crupi R, Cuzzocrea S, et al. Adelmidrol: A New Promising Antioxidant and Anti-Inflammatory Therapeutic Tool in Pulmonary Fibrosis. Antioxidants. 2020; 9(7):601. https://doi.org/10.3390/antiox9070601
Chicago/Turabian StyleFusco, Roberta, Marika Cordaro, Tiziana Genovese, Daniela Impellizzeri, Rosalba Siracusa, Enrico Gugliandolo, Alessio Filippo Peritore, Ramona D’Amico, Rosalia Crupi, Salvatore Cuzzocrea, and et al. 2020. "Adelmidrol: A New Promising Antioxidant and Anti-Inflammatory Therapeutic Tool in Pulmonary Fibrosis" Antioxidants 9, no. 7: 601. https://doi.org/10.3390/antiox9070601