H2S as a Bridge Linking Inflammation, Oxidative Stress and Endothelial Biology: A Possible Defense in the Fight against SARS-CoV-2 Infection?
Abstract
:1. Introduction
2. Hydrogen Sulfide: An Additive Key Factor in Vascular Homeostasis
2.1. Sulfur-Drugs as New Therapeutic Options in Endothelial Dysfunction
2.1.1. H2S Donors
2.1.2. H2S-Hybrid Drugs
2.2. H2S-Producing Compounds: A Further Tool against COVID-19
3. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Medina-Leyte, D.J.; Zepeda-García, O.; Domínguez-Pérez, M.; González-Garrido, A.; Villarreal-Molina, T.; Jacobo-Albavera, L. Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. Int. J. Mol. Sci. 2021, 22, 3850. [Google Scholar] [CrossRef]
- Xu, S.; Ilyas, I.; Little, P.J.; Li, H.; Kamato, D.; Zheng, X.; Luo, S.; Li, Z.; Liu, P.; Han, J.; et al. Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies. Pharmacol Rev. 2021, 73, 924–967. [Google Scholar] [CrossRef]
- Dou, Q.; Wei, X.; Zhou, K.; Yang, S.; Jia, P. Cardiovascular Manifestations and Mechanisms in Patients with COVID-19. Trends Endocrinol. Metab. 2020, 31, 893–904. [Google Scholar] [CrossRef]
- Guzik, T.J.; Mohiddin, S.A.; Dimarco, A.; Patel, V.; Savvatis, K.; Marelli-Berg, F.M.; Madhur, M.S.; Tomaszewski, M.; Maffia, P.; D’Acquisto, F.; et al. COVID-19 and the cardiovascular system: Implications for risk assessment, diagnosis, and treatment options. Cardiovasc. Res. 2020, 116, 1666–1687. [Google Scholar] [CrossRef] [PubMed]
- Pan, L.L.; Qin, M.; Liu, X.H.; Zhu, Y.Z. The Role of Hydrogen Sulfide on Cardiovascular Homeostasis: An Overview with Update on Immunomodulation. Front. Pharmacol. 2017, 8, 686. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ciccone, V.; Genah, S.; Morbidelli, L. Endothelium as a Source and Target of H2S to Improve Its Trophism and Function. Antioxidants (Basel) 2021, 10, 486. [Google Scholar] [CrossRef]
- Wang, R.; Szabo, C.; Ichinose, F.; Ahmed, A.; Whiteman, M.; Papapetropoulos, A. The role of H2S bioavailability in endothelial dysfunction. Trends Pharmacol. Sci. 2015, 36, 568–578. [Google Scholar] [CrossRef] [Green Version]
- Xiao, Q.; Ying, J.; Xiang, L.; Zhang, C. The biologic effect of hydrogen sulfide and its function in various diseases. Medicine (Baltimore) 2018, 97, e13065. [Google Scholar] [CrossRef]
- Wallace, J.L.; Wang, R. Hydrogen sulfide-based therapeutics: Exploiting a unique but ubiquitous gasotransmitter. Nat. Rev. Drug Discov. 2015, 14, 329–345. [Google Scholar] [CrossRef]
- Majtan, T.; Krijt, J.; Sokolová, J.; Křížková, M.; Ralat, M.A.; Kent, J.; Gregory, J.F., 3rd; Kožich, V.; Kraus, J.P. Biogenesis of Hydrogen Sulfide and Thioethers by Cystathionine Beta-Synthase. Antioxid. Redox Signal. 2018, 8, 311–323. [Google Scholar] [CrossRef]
- Kanagy, N.L.; Szabo, C.; Papapetropoulos, A. Vascular biology of hydrogen sulfide. Am. J. Physiol. Cell Physiol. 2017, 312, C537–C549. [Google Scholar] [CrossRef]
- Meng, G.; Zhao, S.; Xie, L.; Han, Y.; Ji, Y. Protein S-sulfhydration by hydrogen sulfide in cardiovascular system. Br. J. Pharmacol. 2018, 175, 1146–1156. [Google Scholar] [CrossRef] [PubMed]
- Altaany, Z.; Ju, Y.; Yang, G.; Wang, R. The coordination of S-sulfhydration, S-nitrosylation, and phosphorylation of endothelial nitric oxide synthase by hydrogen sulfide. Sci. Signal. 2014, 7, ra87. [Google Scholar] [CrossRef] [PubMed]
- Mustafa, A.K.; Sikka, G.; Gazi, S.K.; Steppan, J.; Jung, S.M.; Bhunia, A.K.; Barodka, V.M.; Gazi, F.K.; Barrow, R.K.; Wang, R.; et al. Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ. Res. 2011, 109, 1259–1268. [Google Scholar] [CrossRef]
- Yan, H.; Du, J.; Tang, C. The possible role of hydrogen sulfide on the pathogenesis of spontaneous hypertension in rats. Biochem. Biophys Res. Commun. 2004, 313, 22–27. [Google Scholar] [CrossRef]
- Al-Magableh, M.R.; Kemp-Harper, B.K.; Hart, J.L. Hydrogen sulfide treatment reduces blood pressure and oxidative stress in angiotensin II-induced hypertensive mice. Hypertens Res. 2015, 38, 13–20. [Google Scholar] [CrossRef] [PubMed]
- Whiteman, M.; Armstrong, J.S.; Chu, S.H.; Jia-Ling, S.; Wong, B.S.; Cheung, N.S.; Halliwell, B.; Moore, P.K. The novel neuromodulator hydrogen sulfide: An endogenous peroxynitrite ‘scavenger’? J. Neurochem. 2004, 90, 765–768. [Google Scholar] [CrossRef]
- Yang, G.; Zhao, K.; Ju, Y.; Mani, S.; Cao, Q.; Puukila, S.; Khaper, N.; Wu, L.; Wang, R. Hydrogen sulfide protects against cellular senescence via S-sulfhydration of Keap1 and activation of Nrf2. Antioxid. Redox Signal. 2013, 18, 1906–1919. [Google Scholar] [CrossRef] [PubMed]
- Guo, C.; Liang, F.; Shah Masood, W.; Yan, X. Hydrogen sulfide protected gastric epithelial cell from ischemia/reperfusion injury by Keap1 s-sulfhydration, MAPK dependent anti-apoptosis and NF-κB dependent anti-inflammation pathway. Eur. J. Pharmacol. 2014, 725, 70–78. [Google Scholar] [CrossRef]
- Wen, Y.D.; Wang, H.; Kho, S.H.; Rinkiko, S.; Sheng, X.; Shen, H.M.; Zhu, Y.Z. Hydrogen sulfide protects HUVECs against hydrogen peroxide induced mitochondrial dysfunction and oxidative stress. PLoS ONE 2013, 8, e53147. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, K.; Ju, Y.; Li, S.; Altaany, Z.; Wang, R.; Yang, G. S-sulfhydration of MEK1 leads to PARP-1 activation and DNA damage repair. EMBO Rep. 2014, 15, 792–800. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, L.; Rose, P.; Moore, P.K. Hydrogen sulfide and cell signaling. Annu. Rev. Pharmacol. Toxicol. 2011, 51, 169–187. [Google Scholar] [CrossRef] [Green Version]
- Sen, N.; Paul, B.D.; Gadalla, M.M.; Mustafa, A.K.; Sen, T.; Xu, R.; Kim, S.; Snyder, S.H. Hydrogen sulfide-linked sulfhydration of NF-κB mediates its antiapoptotic actions. Mol. Cell. 2012, 45, 13–24. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pan, L.L.; Liu, X.H.; Gong, Q.H.; Wu, D.; Zhu, Y.Z. Hydrogen sulfide attenuated tumor necrosis factor-α-induced inflammatory signaling and dysfunction in vascular endothelial cells. PLoS ONE 2011, 6, e19766. [Google Scholar] [CrossRef] [Green Version]
- Hu, H.J.; Jiang, Z.S.; Zhou, S.H.; Liu, Q.M. Hydrogen sulfide suppresses angiotensin II-stimulated endothelin-1 generation and subsequent cytotoxicity-induced endoplasmic reticulum stress in endothelial cells via NF-κB. Mol. Med. Rep. 2016, 14, 4729–4740. [Google Scholar] [CrossRef]
- Guan, Q.; Wang, X.; Gao, L.; Chen, J.; Liu, Y.; Yu, C.; Zhang, N.; Zhang, X.; Zhao, J. Hydrogen sulfide suppresses high glucose-induced expression of intercellular adhesion molecule-1 in endothelial cells. J. Cardiovasc. Pharmacol. 2013, 62, 278–284. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Wu, J.; Sun, A.; Sun, Y.; Yu, X.; Liu, N.; Dong, S.; Yang, F.; Zhang, L.; Zhong, X.; et al. Hydrogen sulfide decreases high glucose/palmitate-induced autophagy in endothelial cells by the Nrf2-ROS-AMPK signaling pathway. Cell Biosci. 2016, 6, 33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jain, S.K.; Bull, R.; Rains, J.L.; Bass, P.F.; Levine, S.N.; Reddy, S.; McVie, R.; Bocchini, J.A. Low levels of hydrogen sulfide in the blood of diabetes patients and streptozotocin-treated rats causes vascular inflammation? Antioxid. Redox Signal. 2010, 12, 1333–1337. [Google Scholar] [CrossRef]
- Suzuki, K.; Sagara, M.; Aoki, C.; Tanaka, S.; Aso, Y. Clinical Implication of Plasma Hydrogen Sulfide Levels in Japanese Patients with Type 2 Diabetes. Intern. Med. 2017, 56, 17–21. [Google Scholar] [CrossRef] [Green Version]
- Boubeta, F.M.; Bieza, S.A.; Bringas, M.; Palermo, J.C.; Boechi, L.; Estrin, D.A.; Bari, S.E. Hemeproteins as Targets for Sulfide Species. Antioxid. Redox Signal. 2020, 32, 247–257. [Google Scholar] [CrossRef]
- Ríos-González, B.B.; Román-Morales, E.M.; Pietri, R.; López-Garriga, J. Hydrogen sulfide activation in hemeproteins: The sulfheme scenario. J. Inorg. Biochem. 2014, 133, 78–86. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, Z.; Martin, E.; Sharina, I.; Esposito, I.; Szabo, C.; Bucci, M.; Cirino, G.; Papapetropoulos, A. Regulation of soluble guanylyl cyclase redox state by hydrogen sulfide. Pharmacol. Res. 2016, 111, 556–562. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bauer, C.C.; Boyle, J.P.; Porter, K.E.; Peers, C. Modulation of Ca(2+) signalling in human vascular endothelial cells by hydrogen sulfide. Atherosclerosis 2010, 209, 374–380. [Google Scholar] [CrossRef] [PubMed]
- Moccia, F.; Bertoni, G.; Pla, A.F.; Dragoni, S.; Pupo, E.; Merlino, A.; Mancardi, D.; Munaron, L.; Tanzi, F. Hydrogen sulfide regulates intracellular Ca2+ concentration in endothelial cells from excised rat aorta. Curr. Pharm. Biotechnol. 2011, 12, 1416–1426. [Google Scholar] [CrossRef] [PubMed]
- Szabó, C.; Papapetropoulos, A. Hydrogen sulphide and angiogenesis: Mechanisms and applications. Br. J. Pharmacol. 2011, 164, 853–865. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jiang, B.; Tang, G.; Cao, K.; Wu, L.; Wang, R. Molecular mechanism for H2S-induced activation of K(ATP) channels. Antioxid. Redox Signal. 2010, 12, 1167–1178. [Google Scholar] [CrossRef]
- Tao, H.; Shi, K.H.; Yang, J.J. Vascular endothelial growth factor: A novel potential therapeutic target for hypertension. J. Clin. Hypertens. (Greenwich) 2013, 15, 514. [Google Scholar] [CrossRef]
- Liu, Z.; Han, Y.; Li, L.; Lu, H.; Meng, G.; Li, X.; Shirhan, M.; Peh, M.T.; Xie, L.; Zhou, S.; et al. The hydrogen sulfide donor, GYY4137, exhibits anti-atherosclerotic activity in high fat fed apolipoprotein E(−/−) mice. Br. J. Pharmacol. 2013, 169, 1795–1809. [Google Scholar] [CrossRef] [Green Version]
- Du, C.; Lin, X.; Xu, W.; Zheng, F.; Cai, J.; Yang, J.; Cui, Q.; Tang, C.; Cai, J.; Xu, G.; et al. Sulfhydrated Sirtuin-1 Increasing Its Deacetylation Activity Is an Essential Epigenetics Mechanism of Anti-Atherogenesis by Hydrogen Sulfide. Antioxid. Redox Signal. 2019, 30, 184–197. [Google Scholar] [CrossRef]
- Kram, L.; Grambow, E.; Mueller-Graf, F.; Sorg, H.; Vollmar, B. The anti-thrombotic effect of hydrogen sulfide is partly mediated by an upregulation of nitric oxide synthases. Thromb. Res. 2013, 132, e112–e117. [Google Scholar] [CrossRef] [Green Version]
- Grambow, E.; Mueller-Graf, F.; Delyagina, E.; Frank, M.; Kuhla, A.; Vollmar, B. Effect of the hydrogen sulfide donor GYY4137 on platelet activation and microvascular thrombus formation in mice. Platelets 2014, 25, 166–174. [Google Scholar] [CrossRef]
- Grambow, E.; Leppin, C.; Leppin, K.; Kundt, G.; Klar, E.; Frank, M.; Vollmar, B. The effects of hydrogen sulfide on platelet-leukocyte aggregation and microvascular thrombolysis. Platelets 2017, 28, 509–517. [Google Scholar] [CrossRef]
- Kharma, A.; Grman, M.; Misak, A.; Domínguez-Álvarez, E.; Nasim, M.J.; Ondrias, K.; Chovanec, M.; Jacob, C. Inorganic Polysulfides and Related Reactive Sulfur–Selenium Species from the Perspective of Chemistry. Molecules 2019, 24, 1359. [Google Scholar] [CrossRef] [Green Version]
- Kimura, H. Hydrogen sulfide and polysulfides as signaling molecules. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 2015, 91, 131–159. [Google Scholar] [CrossRef] [Green Version]
- Toohey, J.I. Sulfur signaling: Is the agent sulfide or sulfane? Anal. Biochem. 2011, 413, 1–7. [Google Scholar] [CrossRef]
- Kimura, Y.; Toyofuku, Y.; Koike, S.; Shibuya, N.; Nagahara, N.; Lefer, D.; Ogasawara, Y.; Kimura, H. Identification of H2S3 and H2S produced by 3-mercaptopyruvate sulfurtransferase in the brain. Sci. Rep. 2015, 5, 14774. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Olson, K.R.; Gao, Y.; Arif, F.; Arora, K.; Patel, S.; DeLeon, E.R.; Sutton, T.R.; Feelisch, M.; Cortese-Krott, M.M.; Straub, K.D. Metabolism of hydrogen sulfide (H2S) and Production of Reactive Sulfur Species (RSS) by superoxide dismutase. Redox. Biol. 2018, 15, 74–85. [Google Scholar] [CrossRef] [PubMed]
- Kimura, H. Hydrogen polysulfide (H2Sn) signaling along with hydrogen sulfide (H2S) and nitric oxide (NO). J. Neural Transm. (Vienna) 2016, 123, 1235–1245. [Google Scholar] [CrossRef] [PubMed]
- Kimura, Y.; Koike, S.; Shibuya, N.; Lefer, D.; Ogasawara, Y.; Kimura, H. 3-Mercaptopyruvate sulfurtransferase produces potential redox regulators cysteine- and glutathione-persulfide (Cys-SSH and GSSH) together with signaling molecules H2S2, H2S3 and H2S. Sci. Rep. 2017, 7, 10459. [Google Scholar] [CrossRef] [PubMed]
- Bełtowski, J. Hydrogen sulfide in pharmacology and medicine—An update. Pharmacol. Rep. 2015, 67, 647–658. [Google Scholar] [CrossRef] [PubMed]
- Zaorska, E.; Tomasova, L.; Koszelewski, D.; Ostaszewski, R.; Ufnal, M. Hydrogen Sulfide in Pharmacotherapy, Beyond the Hydrogen Sulfide-Donors. Biomolecules 2020, 10, 323. [Google Scholar] [CrossRef] [Green Version]
- Whiteman, M.; Perry, A.; Zhou, Z.; Bucci, M.; Papapetropoulos, A.; Cirino, G.; Wood, M.E. Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors. Handb. Exp. Pharmacol. 2015, 230, 337–363. [Google Scholar] [CrossRef]
- Whiteman, M.; Li, L.; Rose, P.; Tan, C.H.; Parkinson, D.B.; Moore, P.K. The effect of hydrogen sulfide donors on lipopolysaccharide-induced formation of inflammatory mediators in macrophages. Antioxid. Redox Signal. 2010, 12, 1147–1154. [Google Scholar] [CrossRef] [PubMed]
- Gerő, D.; Torregrossa, R.; Perry, A.; Waters, A.; Le-Trionnaire, S.; Whatmore, J.L.; Wood, M.; Whiteman, M. The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro. Pharmacol. Res. 2016, 113 Pt A, 186–198. [Google Scholar] [CrossRef]
- Rushing, A.M.; Donnarumma, E.; Polhemus, D.J.; Au, K.R.; Victoria, S.E.; Schumacher, J.D.; Li, Z.; Jenkins, J.S.; Lefer, D.J.; Goodchild, T.T. Effects of a novel hydrogen sulfide prodrug in a porcine model of acute limb ischemia. J. Vasc. Surg. 2019, 69, 1924–1935. [Google Scholar] [CrossRef]
- Polhemus, D.J.; Li, Z.; Pattillo, C.B.; Gojon, G., Sr.; Gojon, G., Jr.; Giordano, T.; Krum, H. A novel hydrogen sulfide prodrug, SG1002, promotes hydrogen sulfide and nitric oxide bioavailability in heart failure patients. Cardiovasc. Ther. 2015, 33, 216–226. [Google Scholar] [CrossRef] [PubMed]
- Benavides, G.A.; Squadrito, G.L.; Mills, R.W.; Patel, H.D.; Isbell, T.S.; Patel, R.P.; Darley-Usmar, V.M.; Doeller, J.E.; Kraus, D.W. Hydrogen sulfide mediates the vasoactivity of garlic. Proc. Natl. Acad. Sci. USA 2007, 104, 17977–17982. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sharma, D.K.; Manral, A.; Saini, V.; Singh, A.; Srinivasan, B.P.; Tiwari, M. Novel diallyldisulfide analogs ameliorate cardiovascular remodeling in rats with L-NAME-induced hypertension. Eur. J. Pharmacol. 2012, 691, 198–208. [Google Scholar] [CrossRef]
- Hayashida, R.; Kondo, K.; Morita, S.; Unno, K.; Shintani, S.; Shimizu, Y.; Calvert, J.W.; Shibata, R.; Murohara, T. Diallyl Trisulfide Augments Ischemia-Induced Angiogenesis via an Endothelial Nitric Oxide Synthase-Dependent Mechanism. Circ. J. 2017, 81, 870–878. [Google Scholar] [CrossRef] [Green Version]
- Yang, H.B.; Liu, H.M.; Yan, J.C.; Lu, Z.Y. Effect of Diallyl Trisulfide on Ischemic Tissue Injury and Revascularization in a Diabetic Mouse Model. J. Cardiovasc. Pharmacol. 2018, 71, 367–374. [Google Scholar] [CrossRef]
- Calderone, V.; Martelli, A.; Testai, L.; Citi, V.; Breschi, M.C. Using hydrogen sulfide to design and develop drugs. Expert Opin. Drug. Discov. 2016, 11, 163–175. [Google Scholar] [CrossRef]
- Martelli, A.; Piragine, E.; Citi, V.; Testai, L.; Pagnotta, E.; Ugolini, L.; Lazzeri, L.; Di Cesare Mannelli, L.; Manzo, O.L.; Bucci, M.; et al. Erucin exhibits vasorelaxing effects and antihypertensive activity by H2 S-releasing properties. Br. J. Pharmacol. 2020, 177, 824–835. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, C.S.; Lin, A.H.; Liu, C.T.; Tsai, C.W.; Chang, I.S.; Chen, H.W.; Lii, C.K. Isothiocyanates protect against oxidized LDL-induced endothelial dysfunction by upregulating Nrf2-dependent antioxidation and suppressing NFκB activation. Mol. Nutr. Food Res. 2013, 57, 1918–1930. [Google Scholar] [CrossRef]
- Kashfi, K.; Olson, K.R. Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras. Biochem. Pharmacol. 2013, 85, 689–703. [Google Scholar] [CrossRef] [Green Version]
- Wu, L.; Noyan Ashraf, M.H.; Facci, M.; Wang, R.; Paterson, P.G.; Ferrie, A.; Juurlink, B.H. Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system. Proc. Natl. Acad. Sci. USA 2004, 101, 7094–7099. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nagababu, E.; Steppan, J.; Santhanam, L.; Frank, S.M.; Berkowitz, D.E. Effect of Nitrite and N-acetylcysteine Treatment on Blood Pressure, Arterial Stiffness and Vascular Function in Spontaneously Hypertensive Rats. Free Radic. Biol. Med. 2017, 112, 118–119. [Google Scholar] [CrossRef]
- Sun, Q.; Wang, B.; Li, Y.; Sun, F.; Li, P.; Xia, W.; Zhou, X.; Li, Q.; Wang, X.; Chen, J.; et al. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study. Hypertension 2016, 67, 541–549. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- DiNicolantonio, J.J.; OKeefe, J.H.; McCarty, M.F. Boosting endogenous production of vasoprotective hydrogen sulfide via supplementation with taurine and N-acetylcysteine: A novel way to promote cardiovascular health. Open Heart 2017, 4, e000600. [Google Scholar] [CrossRef] [PubMed]
- Pan, L.L.; Liu, X.H.; Gong, Q.H.; Zhu, Y.Z. S-Propargyl-cysteine (SPRC) attenuated lipopolysaccharide-induced inflammatory response in H9c2 cells involved in a hydrogen sulfide-dependent mechanism. Amino Acids 2011, 41, 205–215. [Google Scholar] [CrossRef] [PubMed]
- Pan, L.L.; Liu, X.H.; Zheng, H.M.; Yang, H.B.; Gong, Q.H.; Zhu, Y.Z. S-propargyl-cysteine, a novel hydrogen sulfide-modulated agent, attenuated tumor necrosis factor-α-induced inflammatory signaling and dysfunction in endothelial cells. Int. J. Cardiol. 2012, 155, 327–332. [Google Scholar] [CrossRef]
- Terzuoli, E.; Monti, M.; Vellecco, V.; Bucci, M.; Cirino, G.; Ziche, M.; Morbidelli, L. Characterization of zofenoprilat as an inducer of functional angiogenesis through increased H2 S availability. Br. J. Pharmacol. 2015, 172, 2961–2973. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Monti, M.; Terzuoli, E.; Ziche, M.; Morbidelli, L. H2S dependent and independent anti-inflammatory activity of zofenoprilat in cells of the vascular wall. Pharmacol. Res. 2016, 113, 426–437. [Google Scholar] [CrossRef]
- Monti, M.; Terzuoli, E.; Ziche, M.; Morbidelli, L. The sulphydryl containing ACE inhibitor Zofenoprilat protects coronary endothelium from Doxorubicin-induced apoptosis. Pharmacol. Res. 2013, 76, 171–181. [Google Scholar] [CrossRef]
- Bucci, M.; Vellecco, V.; Cantalupo, A.; Brancaleone, V.; Zhou, Z.; Evangelista, S.; Calderone, V.; Papapetropoulos, A.; Cirino, G. Hydrogen sulfide accounts for the peripheral vascular effects of zofenopril independently of ACE inhibition. Cardiovasc. Res. 2014, 102, 138–147. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wallace, J.L. Hydrogen sulfide-releasing anti-inflammatory drugs. Trends Pharmacol. Sci. 2007, 28, 501–505. [Google Scholar] [CrossRef]
- Sparatore, A.; Perrino, E.; Tazzari, V.; Giustarini, D.; Rossi, R.; Rossoni, G.; Erdmann, K.; Schröder, H.; Del Soldato, P. Pharmacological profile of a novel H2S-releasing aspirin. Free Radic. Biol. Med. 2009, 46, 586–592. [Google Scholar] [CrossRef]
- Liu, L.; Cui, J.; Song, C.J.; Bian, J.S.; Sparatore, A.; Soldato, P.D.; Wang, X.Y.; Yan, C.D. H2S-releasing aspirin protects against aspirin-induced gastric injury via reducing oxidative stress. PLoS ONE 2012, 7, e46301. [Google Scholar] [CrossRef]
- Gao, L.; Cheng, C.; Sparatore, A.; Zhang, H.; Wang, C. Hydrogen sulfide inhibits human platelet aggregation in vitro in part by interfering gap junction channels: Effects of ACS14, a hydrogen sulfide-releasing aspirin. Heart Lung Circ. 2015, 24, 77–85. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pircher, J.; Fochler, F.; Czermak, T.; Mannell, H.; Kraemer, B.F.; Wörnle, M.; Sparatore, A.; Del Soldato, P.; Pohl, U.; Krötz, F. Hydrogen sulfide-releasing aspirin derivative ACS14 exerts strong antithrombotic effects in vitro and in vivo. Arterioscler. Thromb. Vasc. Biol. 2012, 32, 2884–2891. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, H.; Guo, C.; Zhang, A.; Fan, Y.; Gu, T.; Wu, D.; Sparatore, A.; Wang, C. Effect of S-aspirin, a novel hydrogen-sulfide-releasing aspirin (ACS14), on atherosclerosis in apoE-deficient mice. Eur. J. Pharmacol. 2012, 697, 106–116. [Google Scholar] [CrossRef]
- Huang, Q.; Sparatore, A.; Del Soldato, P.; Wu, L.; Desai, K. Hydrogen sulfide releasing aspirin, ACS14, attenuates high glucose-induced increased methylglyoxal and oxidative stress in cultured vascular smooth muscle cells. PLoS ONE 2014, 9, e97315. [Google Scholar] [CrossRef] [PubMed]
- Li, L.; Rossoni, G.; Sparatore, A.; Lee, L.C.; Del Soldato, P.; Moore, P.K. Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative. Free Radic. Biol. Med. 2007, 42, 706–719. [Google Scholar] [CrossRef] [PubMed]
- Baskar, R.; Sparatore, A.; Del Soldato, P.; Moore, P.K. Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative inhibit rat vascular smooth muscle cell proliferation. Eur. J. Pharmacol. 2008, 594, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020, 382, 727–733. [Google Scholar] [CrossRef]
- Bourgonje, A.R.; Offringa, A.K.; van Eijk, L.E.; Abdulle, A.E.; Hillebrands, J.L.; van der Voort, P.H.J.; van Goor, H.; van Hezik, E.J. N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019. Antioxid. Redox Signal. 2021. [Google Scholar] [CrossRef] [PubMed]
- Herold, T.; Jurinovic, V.; Arnreich, C.; Hellmuth, J.C.; von Bergwelt-Baildon, M.; Klein, M.; Weinberger, T. Level of IL-6 Predicts Respiratory Failure in Hospitalized Symptomatic COVID-19 Patients. medRxiv 2020. [Google Scholar] [CrossRef]
- Trinchieri, G. Interleukin-10 production by effector T cells: Th1 cells show self control. J. Exp. Med. 2007, 204, 239–243. [Google Scholar] [CrossRef]
- McElvaney, O.J.; Hobbs, B.D.; Qiao, D.; McElvaney, O.F.; Moll, M.; McEvoy, N.L.; Clarke, J.; O’Connor, E.; Walsh, S.; Cho, M.H.; et al. A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19. EBioMedicine 2020, 61, 103026. [Google Scholar] [CrossRef]
- Fouad, A.A.; Hafez, H.M.; Hamouda, A. Hydrogen sulfide modulates IL-6/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity. Hum. Exp. Toxicol. 2020, 39, 77–85. [Google Scholar] [CrossRef]
- Renieris, G.; Katrini, K.; Damoulari, C.; Akinosoglou, K.; Psarrakis, C.; Kyriakopoulou, M.; Dimopoulos, G.; Lada, M.; Koufargyris, P.; Giamarellos-Bourboulis, E.J. Serum Hydrogen Sulfide and Outcome Association in Pneumonia by the SARS-CoV-2 Coronavirus. Shock 2020, 54, 633–637. [Google Scholar] [CrossRef]
- Citi, V.; Martelli, A.; Gorica, E.; Brogi, S.; Testai, L.; Calderone, V. Role of hydrogen sulfide in endothelial dysfunction: Pathophysiology and therapeutic approaches. J. Adv. Res. 2020, 27, 99–113. [Google Scholar] [CrossRef] [PubMed]
- Li, T.; Zhao, B.; Wang, C.; Wang, H.; Liu, Z.; Li, W.; Jin, H.; Tang, C.; Du, J. Regulatory effects of hydrogen sulfide on IL-6, IL-8 and IL-10 levels in the plasma and pulmonary tissue of rats with acute lung injury. Exp. Biol. Med. (Maywood) 2008, 233, 1081–1087. [Google Scholar] [CrossRef] [PubMed]
- Flannigan, K.L.; Agbor, T.A.; Blackler, R.W.; Kim, J.J.; Khan, W.I.; Verdu, E.F.; Ferraz, J.G.; Wallace, J.L. Impaired hydrogen sulfide synthesis and IL-10 signaling underlie hyperhomocysteinemia-associated exacerbation of colitis. Proc. Natl. Acad. Sci. USA 2014, 111, 13559–13564. [Google Scholar] [CrossRef] [Green Version]
- Miller, T.W.; Wang, E.A.; Gould, S.; Stein, E.V.; Kaur, S.; Lim, L.; Amarnath, S.; Fowler, D.H.; Roberts, D.D. Hydrogen sulfide is an endogenous potentiator of T cell activation. J. Biol. Chem. 2012, 287, 4211–4221. [Google Scholar] [CrossRef] [Green Version]
- Yang, G. H2S as a potential defense against COVID-19? Am. J. Physiol. Cell Physiol. 2020, 319, C244–C249. [Google Scholar] [CrossRef] [PubMed]
- Danser, A.H.J.; Epstein, M.; Batlle, D. Renin-Angiotensin System Blockers and the COVID-19 Pandemic: At Present There Is No Evidence to Abandon Renin-Angiotensin System Blockers. Hypertension 2020, 75, 1382–1385. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, Y.; Zeng, H.; Gao, L.; Gu, T.; Wang, C.; Zhang, H. Hydrogen Sulfide Attenuates Atherosclerosis in a Partially Ligated Carotid Artery Mouse model via Regulating Angiotensin Converting Enzyme 2 Expression. Front. Physiol. 2017, 8, 782. [Google Scholar] [CrossRef] [Green Version]
- Tain, Y.L.; Hsu, C.N.; Lu, P.C. Early short-term treatment with exogenous hydrogen sulfide postpones the transition from prehypertension to hypertension in spontaneously hypertensive rat. Clin. Exp. Hypertens. 2018, 40, 58–64. [Google Scholar] [CrossRef]
- Li, H.; Ma, Y.; Escaffre, O.; Ivanciuc, T.; Komaravelli, N.; Kelley, J.P.; Coletta, C.; Szabo, C.; Rockx, B.; Garofalo, R.P.; et al. Role of hydrogen sulfide in paramyxovirus infections. J. Virol. 2015, 89, 5557–5568. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Faller, S.; Hausler, F.; Goeft, A.; von Itter, M.A.; Gyllenram, V.; Hoetzel, A.; Spassov, S.G. Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury. Sci Rep. 2018, 8, 14676. [Google Scholar] [CrossRef] [Green Version]
- Benetti, L.R.; Campos, D.; Gurgueira, S.A.; Vercesi, A.E.; Guedes, C.E.; Santos, K.L.; Wallace, J.L.; Teixeira, S.A.; Florenzano, J.; Costa, S.K.; et al. Hydrogen sulfide inhibits oxidative stress in lungs from allergic mice in vivo. Eur. J. Pharmacol. 2013, 698, 463–469. [Google Scholar] [CrossRef] [Green Version]
- Polonikov, A. Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients. ACS Infect. Dis. 2020, 6, 1558–1562. [Google Scholar] [CrossRef] [PubMed]
- De Flora, S.; Grassi, C.; Carati, L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur. Respir. J. 1997, 10, 1535–1541. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Q.; Ju, Y.; Ma, Y.; Wang, T. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: A randomized controlled trial. Medicine (Baltimore) 2018, 97, e13087. [Google Scholar] [CrossRef] [PubMed]
- Benrahmoune, M.; Thérond, P.; Abedinzadeh, Z. The reaction of superoxide radical with N-acetylcysteine. Free Radic. Biol. Med. 2000, 29, 775–782. [Google Scholar] [CrossRef]
- Aldini, G.; Altomare, A.; Baron, G.; Vistoli, G.; Carini, M.; Borsani, L.; Sergio, F. N-Acetylcysteine as an antioxidant and disulphide breaking agent: The reasons why. Free Radic. Res. 2018, 52, 751–762. [Google Scholar] [CrossRef]
- Santus, P.; Corsico, A.; Solidoro, P.; Braido, F.; Di Marco, F.; Scichilone, N. Oxidative stress and respiratory system: Pharmacological and clinical reappraisal of N-acetylcysteine. COPD 2014, 11, 705–717. [Google Scholar] [CrossRef]
- Horowitz, R.I.; Freeman, P.R.; Bruzzese, J. Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases. Respir. Med. Case Rep. 2020, 30, 101063. [Google Scholar] [CrossRef]
- Liu, Y.; Wang, M.; Luo, G.; Qian, X.; Wu, C.; Zhang, Y.; Chen, B.; Leung, E.L.; Tang, Y. Experience of N-acetylcysteine airway management in the successful treatment of one case of critical condition with COVID-19: A case report. Medicine (Baltimore) 2020, 99, e22577. [Google Scholar] [CrossRef]
- Assimakopoulos, S.F.; Marangos, M. N-acetyl-cysteine may prevent COVID-19-associated cytokine storm and acute respiratory distress syndrome. Med. Hypotheses 2020, 140, 109778. [Google Scholar] [CrossRef]
- Dominic, P.; Ahmad, J.; Bhandari, R.; Pardue, S.; Solorzano, J.; Jaisingh, K.; Watts, M.; Bailey, S.R.; Orr, A.W.; Kevil, C.G.; et al. Decreased availability of nitric oxide and hydrogen sulfide is a hallmark of COVID-19. Redox Biol. 2021, 43, 101982. [Google Scholar] [CrossRef]
- Dattilo, M. The role of host defences in Covid 19 and treatments thereof. Mol. Med. 2020, 26, 90. [Google Scholar] [CrossRef]
- Kabil, O.; Yadav, V.; Banerjee, R. Heme-dependent Metabolite Switching Regulates H2S Synthesis in Response to Endoplasmic Reticulum (ER) Stress. J. Biol. Chem. 2016, 291, 16418–16423. [Google Scholar] [CrossRef] [Green Version]
- Liu, W.; Li, H. COVID-19 Disease: ORF8 and Surface Glycoprotein Inhibit Heme Metabolism by Binding to Porphyrin. ChemRxiv Preprint 2020. [Google Scholar] [CrossRef] [Green Version]
- Liu, W.; Li, H. COVID-19: Attacks the 1-Beta chain of hemoglobin and captures the Porphyrin to inhibit human Heme metabolism. ChemRxiv Preprint 2020. [Google Scholar] [CrossRef]
- Mustafa, S.; Weltermann, A.; Fritsche, R.; Marsik, C.; Wagner, O.; Kyrle, P.A.; Eichinger, S. Genetic variation in heme oxygenase 1 (HMOX1) and the risk of recurrent venous thromboembolism. J. Vasc. Surg. 2008, 47, 566–570. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Espinoza, J.A.; González, P.A.; Kalergis, A.M. Modulation of Antiviral Immunity by Heme Oxygenase-1. Am. J. Pathol. 2017, 187, 487–493. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bazhanov, N.; Escaffre, O.; Freiberg, A.N.; Garofalo, R.P.; Casola, A. Broad-Range Antiviral Activity of Hydrogen Sulfide Against Highly Pathogenic RNA Viruses. Sci Rep. 2017, 7, 41029. [Google Scholar] [CrossRef]
- Gorini, F.; Bustaffa, E.; Chatzianagnostou, K.; Bianchi, F.; Vassalle, C. Hydrogen sulfide and cardiovascular disease: Doubts, clues, and interpretation difficulties from studies in geothermal areas. Sci. Total Environ. 2020, 743, 140818. [Google Scholar] [CrossRef]
- Read, E.; Zhu, J.; Yang, G. Disrupted HmS Signaling by Cigarette Smoking and Alcohol Drinking: Evidence from Cellular, Animal, and Clinical Studies. Antioxidants (Basel) 2021, 10, 49. [Google Scholar] [CrossRef]
- Teigen, L.M.; Geng, Z.; Sadowsky, M.J.; Vaughn, B.P.; Hamilton, M.J.; Khoruts, A. Dietary Factors in Sulfur Metabolism and Pathogenesis of Ulcerative Colitis. Nutrients 2019, 11, 931. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Blachier, F.; Beaumont, M.; Kim, E. Cysteine-derived hydrogen sulfide and gut health: A matter of endogenous or bacterial origin. Curr. Opin. Clin. Nutr. Metab. Care 2019, 22, 68–75. [Google Scholar] [CrossRef] [PubMed]
Sulfur Drugs | Effects | Reference |
---|---|---|
Inorganic sulfide salts NaHS and Na2S | Reduction of inflammation, oxidative stress and damage induced by hyperglycemia; promotion of vasorelaxation and neovascularization | [6,52] |
Organic “slow-release” H2S compounds GYY4137 | Vasodilator, antihypertensive, anti-atherosclerotic, anti-thrombotic and anti-inflammatory effects | [38,41] |
Diphosphorothioates AP67 and AP105 | Promotion of high-glucose-induced hyperpolarization of the mitochondrial membrane and inhibition of ROS production in microvascular ECs, | [54] |
H2S prodrug sodium polysulthionate (SG1002) | Promotion of increase in circulating H2S and NO and the consequent endothelial-dependent coronary artery vasorelaxation | [55,56] |
Natural organosulfur compound Garlic Natural isothiocyanates | Promotion of vasorelaxation, lower arterial blood pressure, decreased apoptosis and oxidative stress, angiogenesis Anti-inflammatory and antioxidant effects | [57,58,59,60] [63,64,65] |
N-acetyl-Cysteine (NAC) and taurine | Anti-hypertensive and anti-inflammatory effects | [66,67,68] |
Synthetic cysteine derivatives (S-propyl-cysteine, S-allyl-cysteine and S-propargyl-cysteine) | Increase in H2S levels, anti-inflammatory effects | [69,70] |
H2S-hybrid drug ACE inhibitors: Omaprilat, Remikiren, Macitentan, Bosentan, Vardenafil, Sildenafil | Pro-angiogenic, anti-inflammatory and anti-apoptotic activities Zofenopril: increase in H2S concentration in plasma and vascular wall | [71,72,73] [74] |
H2S-releasing derivatives of NSAIDs | Anti-platelet, antithrombotic and antioxidant effects S-diclofenac (ACS15): anti-inflammatory and antiproliferative effects | [78,79,81] [82,83] |
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
Gorini, F.; Del Turco, S.; Sabatino, L.; Gaggini, M.; Vassalle, C. H2S as a Bridge Linking Inflammation, Oxidative Stress and Endothelial Biology: A Possible Defense in the Fight against SARS-CoV-2 Infection? Biomedicines 2021, 9, 1107. https://doi.org/10.3390/biomedicines9091107
Gorini F, Del Turco S, Sabatino L, Gaggini M, Vassalle C. H2S as a Bridge Linking Inflammation, Oxidative Stress and Endothelial Biology: A Possible Defense in the Fight against SARS-CoV-2 Infection? Biomedicines. 2021; 9(9):1107. https://doi.org/10.3390/biomedicines9091107
Chicago/Turabian StyleGorini, Francesca, Serena Del Turco, Laura Sabatino, Melania Gaggini, and Cristina Vassalle. 2021. "H2S as a Bridge Linking Inflammation, Oxidative Stress and Endothelial Biology: A Possible Defense in the Fight against SARS-CoV-2 Infection?" Biomedicines 9, no. 9: 1107. https://doi.org/10.3390/biomedicines9091107