Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia
Abstract
:1. Introduction
2. Results
2.1. Prenatal H2 Administration Did Not Change Lung Weight but Improved Blood Gas Results in CDH Rats
2.2. The Effects of Prenatal H2 Administration on Alveolarization and Pulmonary Artery Remodeling in CDH Rats
2.3. Prenatal H2 Administration Reduced Oxidative Stress but Did Not Affect PDGFRβ Expression in the Fetal Pulmonary Arterial Wall in CDH
2.4. Prenatal H2 Administration Ameliorated Surfactant Protein A Production Insufficiency in Lungs of Pups with CDH
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Animals
4.3. Experimental Design
4.4. Tissue Collection
4.5. Gasometric Evaluation
4.6. Histological Analysis
4.7. Immunohistochemistry
4.8. Real-Time Polymerase Chain Reaction (PCR)
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Montalva, L.; Antounians, L.; Zani, A. Pulmonary hypertension secondary to congenital diaphragmatic hernia: Factors and pathways involved in pulmonary vascular remodeling. Pediatr. Res. 2019, 85, 754–768. [Google Scholar] [CrossRef]
- Lally, K.P. Congenital diaphragmatic hernia—The past 25 (or so) years. J. Pediatr. Surg. 2016, 51, 695–698. [Google Scholar] [CrossRef] [PubMed]
- Garne, E.; Haeusler, M.; Barisic, I.; Gjergja, R.; Stoll, C.; Clementi, M.; Euroscan Study, G. Congenital diaphragmatic hernia: Evaluation of prenatal diagnosis in 20 European regions. Ultrasound. Obstet. Gynecol. 2002, 19, 329–333. [Google Scholar] [CrossRef]
- Rosenzweig, E.B.; Abman, S.H.; Adatia, I.; Beghetti, M.; Bonnet, D.; Haworth, S.; Ivy, D.D.; Berger, R.M.F. Paediatric pulmonary arterial hypertension: Updates on definition, classification, diagnostics and management. Eur. Respir. J. 2019, 53, 1801916. [Google Scholar] [CrossRef]
- Mous, D.S.; Kool, H.M.; Wijnen, R.; Tibboel, D.; Rottier, R.J. Pulmonary vascular development in congenital diaphragmatic hernia. Eur. Respir. Rev. 2018, 27, 170104. [Google Scholar] [CrossRef]
- Sluiter, I.; van der Horst, I.; van der Voorn, P.; Boerema-de Munck, A.; Buscop-van Kempen, M.; de Krijger, R.; Tibboel, D.; Reiss, I.; Rottier, R.J. Premature differentiation of vascular smooth muscle cells in human congenital diaphragmatic hernia. Exp. Mol. Pathol 2013, 94, 195–202. [Google Scholar] [CrossRef] [PubMed]
- Deprest, J.; Brady, P.; Nicolaides, K.; Benachi, A.; Berg, C.; Vermeesch, J.; Gardener, G.; Gratacos, E. Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial. Semin. Fetal. Neonatal. Med. 2014, 19, 338–348. [Google Scholar] [CrossRef]
- Deprest, J.A.; Nicolaides, K.H.; Benachi, A.; Gratacos, E.; Ryan, G.; Persico, N.; Sago, H.; Johnson, A.; Wielgoś, M.; Berg, C.; et al. Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia. N. Engl. J. Med. 2021, 385, 107–118. [Google Scholar] [CrossRef]
- Kashyap, A.; DeKoninck, P.; Crossley, K.; Thio, M.; Polglase, G.; Russo, F.M.; Deprest, J.; Hooper, S.; Hodges, R. Antenatal Medical Therapies to Improve Lung Development in Congenital Diaphragmatic Hernia. Am. J. Perinatol. 2018, 35, 823–836. [Google Scholar] [CrossRef]
- Aras-López, R.; Tovar, J.A.; Martínez, L. Possible role of increased oxidative stress in pulmonary hypertension in experimental diaphragmatic hernia. Pediatr. Surg. Int. 2016, 32, 141–145. [Google Scholar] [CrossRef]
- Dingemann, J.; Doi, T.; Ruttenstock, E.; Puri, P. Abnormal platelet-derived growth factor signaling accounting for lung hypoplasia in experimental congenital diaphragmatic hernia. J. Pediatr. Surg. 2010, 45, 1989–1994. [Google Scholar] [CrossRef]
- Hirako, S.; Tsuda, H.; Ito, F.; Okazaki, Y.; Hirayama, T.; Nagasawa, H.; Nakano, T.; Imai, K.; Kotani, T.; Kikkawa, F.; et al. Role of catalytic iron and oxidative stress in nitrofen-induced congenital diaphragmatic hernia and its amelioration by Saireito (TJ-114). J. Clin. Biochem. Nutr. 2017, 61, 176–182. [Google Scholar] [CrossRef] [Green Version]
- Ohsawa, I.; Ishikawa, M.; Takahashi, K.; Watanabe, M.; Nishimaki, K.; Yamagata, K.; Katsura, K.; Katayama, Y.; Asoh, S.; Ohta, S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 2007, 13, 688–694. [Google Scholar] [CrossRef] [PubMed]
- Ohta, S. Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions. Curr. Pharm. Des. 2021, 27, 595–609. [Google Scholar] [CrossRef]
- Hattori, Y.; Kotani, T.; Tsuda, H.; Mano, Y.; Tu, L.; Li, H.; Hirako, S.; Ushida, T.; Imai, K.; Nakano, T.; et al. Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury. Free Radic. Res. 2015, 49, 1026–1037. [Google Scholar] [CrossRef]
- Imai, K.; Kotani, T.; Tsuda, H.; Mano, Y.; Nakano, T.; Ushida, T.; Li, H.; Miki, R.; Sumigama, S.; Iwase, A.; et al. Neuroprotective potential of molecular hydrogen against perinatal brain injury via suppression of activated microglia. Free Radic Biol. Med. 2016, 91, 154–163. [Google Scholar] [CrossRef]
- Mano, Y.; Kotani, T.; Ito, M.; Nagai, T.; Ichinohashi, Y.; Yamada, K.; Ohno, K.; Kikkawa, F.; Toyokuni, S. Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion. Free Radic. Biol. Med. 2014, 69, 324–330. [Google Scholar] [CrossRef]
- Nakano, T.; Kotani, T.; Mano, Y.; Tsuda, H.; Imai, K.; Ushida, T.; Li, H.; Miki, R.; Sumigama, S.; Sato, Y.; et al. Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury. J. Clin. Biochem. Nutr. 2015, 57, 178–182. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kishimoto, Y.; Kato, T.; Ito, M.; Azuma, Y.; Fukasawa, Y.; Ohno, K.; Kojima, S. Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects. J. Thorac. Cardiovasc. Surg. 2015, 150, 645–654.e3. [Google Scholar] [CrossRef] [Green Version]
- Montani, D.; Chaumais, M.C.; Guignabert, C.; Gunther, S.; Girerd, B.; Jais, X.; Algalarrondo, V.; Price, L.C.; Savale, L.; Sitbon, O.; et al. Targeted therapies in pulmonary arterial hypertension. Pharmacol. Ther. 2014, 141, 172–191. [Google Scholar] [CrossRef]
- Chang, Y.T.; Ringman Uggla, A.; Osterholm, C.; Tran, P.K.; Eklöf, A.C.; Lengquist, M.; Hedin, U.; Tran-Lundmark, K.; Frenckner, B. Antenatal imatinib treatment reduces pulmonary vascular remodeling in a rat model of congenital diaphragmatic hernia. Am. J. Physiol.-Lung. Cell. Mol. Physiol. 2012, 302, L1159–L1166. [Google Scholar] [CrossRef] [PubMed]
- Okolo, F.C.; Zhang, G.; Rhodes, J.; Potoka, D.A. Intra-amniotic Sildenafil Treatment Modulates Vascular Smooth Muscle Cell Phenotype in the Nitrofen Model of Congenital Diaphragmatic Hernia. Sci. Rep. 2018, 8, 17668. [Google Scholar] [CrossRef]
- Dalvi, P.N.; Gupta, V.G.; Griffin, B.R.; O’Brien-Ladner, A.; Dhillon, N.K. Ligand-Independent Activation of Platelet-Derived Growth Factor Receptor β during Human Immunodeficiency Virus-Transactivator of Transcription and Cocaine-Mediated Smooth Muscle Hyperplasia. Am. J. Respir. Cell Mol. Biol. 2015, 53, 336–345. [Google Scholar] [CrossRef] [Green Version]
- Jiang, B.; Yamamura, S.; Nelson, P.R.; Mureebe, L.; Kent, K.C. Differential effects of platelet-derived growth factor isotypes on human smooth muscle cell proliferation and migration are mediated by distinct signaling pathways. Surgery 1996, 120, 427–431. [Google Scholar] [CrossRef]
- Candilera, V.; Bouchè, C.; Schleef, J.; Pederiva, F. Lung growth factors in the amniotic fluid of normal pregnancies and with congenital diaphragmatic hernia. J. Matern.-Fetal Neonatal Med. 2016, 29, 2104–2108. [Google Scholar] [CrossRef] [Green Version]
- Gupta, V.S.; Harting, M.T. Congenital diaphragmatic hernia-associated pulmonary hypertension. Semin. Perinatol 2020, 44, 151167. [Google Scholar] [CrossRef]
- Ranchoux, B.; Meloche, J.; Paulin, R.; Boucherat, O.; Provencher, S.; Bonnet, S. DNA Damage and Pulmonary Hypertension. Int. J. Mol. Sci. 2016, 17, 990. [Google Scholar] [CrossRef] [Green Version]
- Wedgwood, S.; Steinhorn, R.H.; Lakshminrusimha, S. Optimal oxygenation and role of free radicals in PPHN. Free Radic. Biol. Med. 2019, 142, 97–106. [Google Scholar] [CrossRef] [PubMed]
- Frijhoff, J.; Dagnell, M.; Augsten, M.; Beltrami, E.; Giorgio, M.; Ostman, A. The mitochondrial reactive oxygen species regulator p66Shc controls PDGF-induced signaling and migration through protein tyrosine phosphatase oxidation. Free Radic. Biol. Med. 2014, 68, 268–277. [Google Scholar] [CrossRef]
- Kruk, J.S.; Vasefi, M.S.; Heikkila, J.J.; Beazely, M.A. Reactive oxygen species are required for 5-HT-induced transactivation of neuronal platelet-derived growth factor and TrkB receptors, but not for ERK1/2 activation. PLoS ONE 2013, 8, e77027. [Google Scholar] [CrossRef]
- Shimizu, H.; Hirose, Y.; Nishijima, F.; Tsubakihara, Y.; Miyazaki, H. ROS and PDGF-beta [corrected] receptors are critically involved in indoxyl sulfate actions that promote vascular smooth muscle cell proliferation and migration. Am. J. Physiol. Cell Physiol. 2009, 297, C389–C396. [Google Scholar] [CrossRef]
- Kappert, K.; Sparwel, J.; Sandin, A.; Seiler, A.; Siebolts, U.; Leppänen, O.; Rosenkranz, S.; Ostman, A. Antioxidants relieve phosphatase inhibition and reduce PDGF signaling in cultured VSMCs and in restenosis. Arterioscler. Thromb. Vasc. Biol. 2006, 26, 2644–2651. [Google Scholar] [CrossRef] [Green Version]
- Schmidt, A.F.; Gonçalves, F.L.; Figueira, R.L.; Scorletti, F.; Peiró, J.L.; Sbragia, L. Combined antenatal therapy with retinoic acid and tracheal occlusion in a rat model of congenital diaphragmatic hernia. Pediatr. Surg. Int. 2016, 32, 591–598. [Google Scholar] [CrossRef]
- Schmidt, A.F.; Gonçalves, F.L.; Nassr, A.C.; Pereira, L.A.; Farmer, D.; Sbragia, L. Antenatal steroid and tracheal occlusion restore vascular endothelial growth factor receptors in congenital diaphragmatic hernia rat model. Am. J. Obstet. Gynecol. 2010, 203, 184.e13–184.e20. [Google Scholar] [CrossRef] [PubMed]
- Schmidt, A.F.; Goncalves, F.L.; Regis, A.C.; Gallindo, R.M.; Sbragia, L. Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat. Am. J. Obstet Gynecol. 2012, 207, 76.e25–76.e32. [Google Scholar] [CrossRef] [PubMed]
- Muramatsu, Y.; Ito, M.; Oshima, T.; Kojima, S.; Ohno, K. Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats. Pediatr. Pulmonol. 2016, 51, 928–935. [Google Scholar] [CrossRef]
- Ivanov, D.; Mazzoccoli, G.; Anderson, G.; Linkova, N.; Dyatlova, A.; Mironova, E.; Polyakova, V.; Kvetnoy, I.; Evsyukova, I.; Carbone, A.; et al. Melatonin, Its Beneficial Effects on Embryogenesis from Mitigating Oxidative Stress to Regulating Gene Expression. Int. J. Mol. Sci. 2021, 22, 5885. [Google Scholar] [CrossRef]
- Liu, H.; Li, X.; Yu, W.Q.; Liu, C.X. Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced congenital diaphragmatic hernia rat model. Int. J. Mol. Med. 2018, 42, 2373–2382. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Whitsett, J.A.; Weaver, T.E. Alveolar development and disease. Am. J. Respir. Cell Mol. Biol. 2015, 53, 1–7. [Google Scholar] [CrossRef] [Green Version]
- Mysore, M.R.; Margraf, L.R.; Jaramillo, M.A.; Breed, D.R.; Chau, V.L.; Arévalo, M.; Moya, F.R. Surfactant protein A is decreased in a rat model of congenital diaphragmatic hernia. Am. J. Respir. Crit. Care Med. 1998, 157, 654–657. [Google Scholar] [CrossRef]
- Fox, Z.D.; Jiang, G.; Ho, K.K.Y.; Walker, K.A.; Liu, A.P.; Kunisaki, S.M. Fetal lung transcriptome patterns in an ex vivo compression model of diaphragmatic hernia. J. Surg. Res. 2018, 231, 411–420. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cogo, P.E.; Zimmermann, L.J.; Rosso, F.; Tormena, F.; Gamba, P.; Verlato, G.; Baritussio, A.; Carnielli, V.P. Surfactant synthesis and kinetics in infants with congenital diaphragmatic hernia. Am. J. Respir. Crit. Care Med. 2002, 166, 154–158. [Google Scholar] [CrossRef]
- Khalak, R.; Huyck, H.L.; Pryhuber, G.S. Antagonistic effects of pyrrolidine dithiocarbamate and N-acetyl-L-cysteine on surfactant protein A and B mRNAs. Exp. Lung Res. 1999, 25, 479–493. [Google Scholar] [CrossRef] [PubMed]
- Ostojic, S.M. Molecular hydrogen in sports medicine: New therapeutic perspectives. Int. J. Sports Med. 2015, 36, 273–279. [Google Scholar] [CrossRef] [Green Version]
- Mikami, T.; Tano, K.; Lee, H.; Lee, H.; Park, J.; Ohta, F.; LeBaron, T.W.; Ohta, S. Drinking hydrogen water enhances endurance and relieves psychometric fatigue: A randomized, double-blind, placebo-controlled study (1). Can. J. Physiol. Pharmacol. 2019, 97, 857–862. [Google Scholar] [CrossRef] [PubMed]
- Sim, M.; Kim, C.S.; Shon, W.J.; Lee, Y.K.; Choi, E.Y.; Shin, D.M. Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: A randomized, double-blind, controlled trial. Sci. Rep. 2020, 10, 12130. [Google Scholar] [CrossRef]
- Yoritaka, A.; Takanashi, M.; Hirayama, M.; Nakahara, T.; Ohta, S.; Hattori, N. Pilot study of H₂ therapy in Parkinson’s disease: A randomized double-blind placebo-controlled trial. Mov. Disord. 2013, 28, 836–839. [Google Scholar] [CrossRef]
- Cole, A.R.; Raza, A.; Ahmed, H.; Polizzotti, B.D.; Padera, R.F.; Andrews, N.; Kheir, J.N. Safety of inhaled hydrogen gas in healthy mice. Med. Gas. Res. 2019, 9, 133–138. [Google Scholar] [CrossRef]
- Nakano, T.; Kotani, T.; Imai, K.; Iitani, Y.; Ushida, T.; Tsuda, H.; Li, H.; Iwase, A.; Toyokuni, S.; Kikkawa, F. Effect of molecular hydrogen on uterine inflammation during preterm labour. Biomed. Rep. 2018, 8, 454–460. [Google Scholar] [CrossRef]
- Ushida, T.; Kotani, T.; Tsuda, H.; Imai, K.; Nakano, T.; Hirako, S.; Ito, Y.; Li, H.; Mano, Y.; Wang, J.; et al. Molecular hydrogen ameliorates several characteristics of preeclampsia in the Reduced Uterine Perfusion Pressure (RUPP) rat model. Free Radic. Biol. Med. 2016, 101, 524–533. [Google Scholar] [CrossRef]
- Imai, K.; Kotani, T.; Tsuda, H.; Nakano, T.; Ushida, T.; Iwase, A.; Nagai, T.; Toyokuni, S.; Suzumura, A.; Kikkawa, F. Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model. Sci. Rep. 2018, 8, 9221. [Google Scholar] [CrossRef]
- Ito, Y.; Tsuda, H.; Imai, K.; Miki, R.; Miura, M.; Tachi, A.; Tano, S.; Hirako-Takamura, S.; Moriyama, Y.; Ushida, T.; et al. Vitamin D improves pulmonary function in a rat model for congenital diaphragmatic hernia. Arch. Biochem. Biophys. 2021, 700, 108769. [Google Scholar] [CrossRef]
- Luong, C.; Rey-Perra, J.; Vadivel, A.; Gilmour, G.; Sauve, Y.; Koonen, D.; Walker, D.; Todd, K.G.; Gressens, P.; Kassiri, Z.; et al. Antenatal sildenafil treatment attenuates pulmonary hypertension in experimental congenital diaphragmatic hernia. Circulation 2011, 123, 2120–2131. [Google Scholar] [CrossRef] [Green Version]
- Hirako, S.; Tsuda, H.; Kotani, T.; Sumigama, S.; Mano, Y.; Nakano, T.; Imai, K.; Li, H.; Toyokuni, S.; Kikkawa, F. Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia. Phytother. Res. 2016, 30, 1474–1480. [Google Scholar] [CrossRef]
- Watanabe, Y.; Tsuda, H.; Kotani, T.; Sumigama, S.; Mano, Y.; Hayakawa, M.; Sato, Y.; Kikkawa, F. Amniotic lamellar body count and congenital diaphragmatic hernia in humans and in a rat model. Pediatr. Res 2013, 73, 344–348. [Google Scholar] [CrossRef]
- Nogueira-Silva, C.; Carvalho-Dias, E.; Piairo, P.; Nunes, S.; Baptista, M.J.; Moura, R.S.; Correia-Pinto, J. Local fetal lung renin-angiotensin system as a target to treat congenital diaphragmatic hernia. Mol. Med. 2012, 18, 231–243. [Google Scholar] [CrossRef] [Green Version]
- Crowley, G.; Kwon, S.; Caraher, E.J.; Haider, S.H.; Lam, R.; Batra, P.; Melles, D.; Liu, M.; Nolan, A. Quantitative lung morphology: Semi-automated measurement of mean linear intercept. BMC Pulm. Med. 2019, 19, 206. [Google Scholar] [CrossRef]
- Morrison, T.B.; Weis, J.J.; Wittwer, C.T. Quantification of low-copy transcripts by continuous SYBR Green I monitoring during amplification. Biotechniques 1998, 24, 954–958, 960, 962. [Google Scholar]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Miura, M.; Imai, K.; Tsuda, H.; Miki, R.; Tano, S.; Ito, Y.; Hirako-Takamura, S.; Moriyama, Y.; Ushida, T.; Iitani, Y.; et al. Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia. Int. J. Mol. Sci. 2021, 22, 9500. https://doi.org/10.3390/ijms22179500
Miura M, Imai K, Tsuda H, Miki R, Tano S, Ito Y, Hirako-Takamura S, Moriyama Y, Ushida T, Iitani Y, et al. Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia. International Journal of Molecular Sciences. 2021; 22(17):9500. https://doi.org/10.3390/ijms22179500
Chicago/Turabian StyleMiura, Mayo, Kenji Imai, Hiroyuki Tsuda, Rika Miki, Sho Tano, Yumiko Ito, Shima Hirako-Takamura, Yoshinori Moriyama, Takafumi Ushida, Yukako Iitani, and et al. 2021. "Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia" International Journal of Molecular Sciences 22, no. 17: 9500. https://doi.org/10.3390/ijms22179500