Potential application of gaseous nitric oxide as a topical antimicrobial agent
Abstract
The presence of bacterial colonization in non-healing wounds and burn injuries interferes significantly with the normal process of healing. Recent evidence suggests that nitric oxide (NO) plays an important role in host defense against infection and regulates wound healing and angiogenesis. We investigated the potential application of a medical-grade gaseous form of NO (gNO) as a novel antibacterial agent in wound infection. Using a continuous horizontal-flow delivery system, the antibacterial activity of gNO was tested in vitro against a range of pathogens, including clinical isolates of Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Group B Streptococcus, Pseudomonas aeruginosa, and Candida albicans. To probe the effect of topical application of gNO on the human skin, the proliferation and extracellular matrix gene expression of human dermal fibroblasts in culture were also analyzed by (3)H-thymidine incorporation assay and Northern blot techniques, respectively. Potent bacteriocidal activity was observed at 200 ppm gNO with an average of 4.1 +/- 1.1 h to completely stop bacterial growth. Interestingly, this dose of gNO did not show any cytotoxic effect in human dermal fibroblasts in culture exposed for up to 48 h. Analysis of gene transcription in fibroblasts revealed a significant increase in MMP-1 mRNA expression as early as 2 h post-exposure to gNO. Although to a lesser degree, a significant reduction in type I procollagen was also observed in the same fibroblasts. The results of this study suggest that exogenous gaseous NO has potent significant antibacterial properties that can be beneficial in reducing bacterial burden in infected wound in burn injuries or non-healing ulcers.
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The dose of NO required to kill bacteria (e.g., 200 ppm gaseous NO) does not show cytotoxic effects in human dermal fibroblasts when exposed for 48 h.
“Moreover, the dose of NO required to kill bacteria (e.g., 200 ppm of gaseous NO)281,282,285 does not show any cytotoxic effects in human dermal fibroblasts when exposed for 48 h.216,220”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [281]
NO possesses broad-spectrum antibacterial activity against both gram-positive and gram-negative bacteria, including MRSA.
“Of note, NO possesses broad-spectrum antibacterial activity against both gram-positive and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).219,281”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [281]
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Cites
Nitric oxide synthases in mammals
Knowles, R. G., & Moncada, S. (1994) · Biochemical Journal · doi:10.1042/bj2980249 · Cited by 2,752 · see citing works
Nitric oxide, an autocrine regulator of wound fibroblast synthetic function
Schäffer, M. R., Efron, P. A., Thornton, F. J., Klingel, K., Gross, S. S., & Barbul, A. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.5.2375 · Cited by 260 · see citing works
Antimicrobial effect of acidified nitrite on dermatophyte fungi candida and bacterial skin pathogens
Weller, R., Price, R. J., Ormerod, A. D., Benjamin, N., & Leifert, C. (2001) · Journal of Applied Microbiology · doi:10.1046/j.1365-2672.2001.01291.x · Cited by 134 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nitric oxide release: part III. Measurement and reporting.
Coneski, P. N., & Schoenfisch, M. (2012) · Chemical Society Reviews · doi:10.1039/c2cs15271a · Cited by 1,023 · see citing works
The Role of Acidification for Antimicrobial Activity of Atmospheric Pressure Plasma in Liquids
Oehmigen, K., Hähnel, M., Brandenburg, R., Wilke, C., Weltmann, K., & von Woedtke, T. (2010) · Plasma Processes and Polymers · doi:10.1002/ppap.200900077 · Cited by 697 · see citing works
The potential of nitric oxide releasing therapies as antimicrobial agents
Schairer, D. O., Chouake, J. S., Nosanchuk, J. D., & Friedman, A. (2012) · Virulence · doi:10.4161/viru.20328 · Cited by 570 · see citing works
“The lack of bacterial resistance is attributed to the multiple mechanisms of NO generated bacterial toxicity.(5,6,37-40) The versatility of NO allows it to quickly penetrate microbial cell membranes, where various nitrosative and oxidative reactions can proceed, as discussed above.”
BackgroundAnti-biofilm efficacy of nitric oxide-releasing silica nanoparticles
Hetrick, E. M., Shin, J. H., Paul, H. S., & Schoenfisch, M. H. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.01.052 · Cited by 408 · see citing works
Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles
Hetrick, E. M., Shin, J. H., Stasko, N., Johnson, C. B., Wespe, D. A., Holmuhamedov, E., & Schoenfisch, M. H. (2008) · ACS Nano · doi:10.1021/nn700191f · Cited by 365 · see citing works
Gas‐Generating Nanoplatforms: Material Chemistry, Multifunctionality, and Gas Therapy
Yu, L., Hu, P., & Chen, Y. (2018) · Advanced Materials · doi:10.1002/adma.201801964 · Cited by 361 · see citing works
Quenching the quorum sensing system: potential antibacterial drug targets
Kalia, V., & Purohit, H. (2011) · Critical reviews in microbiology · doi:10.3109/1040841x.2010.532479 · Cited by 303 · see citing works
“Nitric oxide is a reactive free radical which kills cells within established biofilms (Barraud et al. 2006; Ghaffari et al. 2006; Hetrick et al. 2008; Hetrick et al. 2009).”
BackgroundGao, Q., Zhang, X., Yin, W.-Y., Ma, D.-Q., Xie, C.-J., Zheng, L.-R., Dong, X.-H., Mei, L., Yu, J., Wang, C., et al. (2018) · Small · doi:10.1002/smll.201802290 · Cited by 297
Wo, Y., Brisbois, E. J., Bartlett, R. H., & Meyerhoff, M. E. (2016) · Biomaterials Science · doi:10.1039/c6bm00271d · Cited by 251 · see citing works
Martinez, L. R., Han, G., Chacko, M., Mihu, M. R., Jacobson, M., Gialanella, P., Friedman, A. J., Nosanchuk, J. D., & Friedman, J. M. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.95 · Cited by 244 · see citing works
“Topically applied nitric oxide (NO) is a potentially useful preventive and therapeutic strategy against superficial skin infections, including MRSA infections (Ghaffari et al., 2006).”
Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases
Barraud, N., Kelso, M. J., Rice, S., & Kjelleberg, S. J. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612820666140905112822 · Cited by 255 · see citing works
“aeruginosa and Candida albicans [97].”
Beneficial effects of UV radiation other than via vitamin D production
Juzeniene, A., & Moan, J. E. (2012) · Dermato-Endocrinology · doi:10.4161/derm.20013 · Cited by 226 · see citing works
Jamming bacterial communication: New approaches for the treatment of infectious diseases
Njoroge, J. W., & Sperandio, V. (2009) · EMBO Molecular Medicine · doi:10.1002/emmm.200900032 · Cited by 210
“NO is a reactive-free radical normally produced by phagocytes as part of the immune response to bacteria (Ghaffari et al, 2006).”
BackgroundSchaefer, A. L., Cook, N. J., Church, J. S., Basarab, J., Perry, B., Miller, C., & Tong, A. K. W. (2007) · Research in Veterinary Science · doi:10.1016/j.rvsc.2007.01.008 · Cited by 196 · see citing works
“(2005) and Ghaffari et al.”
Self-citationFriedman, A., Han, G., Navati, M., Chacko, M., Gunther, L., Alfieri, A., & Friedman, J. (2008) · Nitric oxide · doi:10.1016/j.niox.2008.04.003 · Cited by 193 · see citing works
Examination of bacterial resistance to exogenous nitric oxide
Privett, B. J., Broadnax, A. D., Bauman, S. J., Riccio, D. A., & Schoenfisch, M. H. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.02.002 · Cited by 206 · see citing works
“aureus was not capable of developing resistance to exogenous gaseous NO; however, NO exposure was intermittent with discontinuous selective pressure against the NO-susceptible bacteria.[15,55,56,57] Herein, we report a thorough bacterial resistance study using both spontaneous mutation and serial passage mutagenesis a…”
BackgroundCold atmospheric plasma manipulation of proteins in food systems
Tolouie, H., Mohammadifar, M. A., Ghomi, H., & Hashemi, M. (2017) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2017.1335689 · Cited by 214 · see citing works
“Bacteria inactivation using gaseous NO in a liquid phase was demonstrated by Ghaffari et al. (2006).”
Jones, M. L., Ganopolsky, J. G., Labbé, A., Wahl, C., & Prakash, S. (2010) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-010-2733-x · Cited by 196 · see citing works
“Still other groups have tried to control the delivery of free gas using a tank of compressed NO, controller, regulator, delivering the gas through a tube to an adhesive patch (Ghaffari et al. 2006; Ghaffari et al. 2007).”
BackgroundRios-Santos, F., Alves-Filho, J., Souto, F. O., Spiller, F., Freitas, A., Lotufo, C., Soares, M., dos Santos, R. D., Teixeira, M., & Cunha, F. D. Q. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200601-103oc · Cited by 149 · see citing works
“Thus, although NO production may be relevant for the ability of a host to deal with an infectious insult (14, 15 ), overproduction of NO in the circulation prevents neutrophil migration and might be detrimental to the outcome of sepsis.”
BackgroundNitric oxide-releasing chitosan oligosaccharides as antibacterial agents
Lu, Y., Slomberg, D. L., & Schoenfisch, M. H. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.015 · Cited by 149 · see citing works
Influence of Scaffold Size on Bactericidal Activity of Nitric Oxide-Releasing Silica Nanoparticles
Carpenter, A. W., Slomberg, D. L., Rao, K. S., & Schoenfisch, M. H. (2011) · ACS Nano · doi:10.1021/nn202054f · Cited by 134 · see citing works
Carpenter, A. W., Worley, B. V., Slomberg, D. L., & Schoenfisch, M. H. (2012) · Biomacromolecules · doi:10.1021/bm301108x · Cited by 132 · see citing works
Zhou, X., Wang, H., Zhang, J., Li, X., Wu, Y., Wei, Y.-Z., Ji, S.-L., Kong, D.-L., & Zhao, Q. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.03.011 · Cited by 130 · see citing works
Han, G., Martinez, L. R., Mihu, M., Friedman, A., Friedman, J., & Nosanchuk, J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007804 · Cited by 125 · see citing works
“Topically applied nitric oxide (NO) is a potentially useful preventive and therapeutic strategy against superficial skin infections, including MRSA infections [6,7].”
BackgroundNitric Oxide-Releasing Dendrimers as Antibacterial Agents
Sun, B., Slomberg, D. L., Chudasama, S. L., Lu, Y., & Schoenfisch, M. H. (2012) · Biomacromolecules · doi:10.1021/bm301109c · Cited by 126 · see citing works
Deppisch, C., Herrmann, G., Graepler-Mainka, U., Wirtz, H., Heyder, S., Engel, C., Marschal, M., Miller, C. C., & Riethmüller, J. (2016) · Infection · doi:10.1007/s15010-016-0879-x · Cited by 115 · see citing works
Self-citationMihu, M., Sandkovsky, U., Han, G., Friedman, J., Nosanchuk, J., & Martinez, L. R. (2010) · Virulence · doi:10.4161/viru.1.2.10038 · Cited by 112 · see citing works
“The topical application of nitric oxide (NO) has the capacity to prevent and treat skin infections, including Methicillinresistant Staphylococcus aureus (MRSA) infections.(9,10) NO modulates immune responses and modifies wound healing.”
BackgroundMiller, C., McMullin, B., Ghaffari, A., Stenzler, A., Pick, N., Roscoe, D. L., Ghahary, A., ROAD, J. D., & Av‐Gay, Y. (2008) · Nitric Oxide · doi:10.1016/j.niox.2008.08.002 · Cited by 105 · see citing works
Self-citationNew approaches from nanomedicine for treating leishmaniasis
Gutiérrez, V., Seabra, A. B., Reguera, R. M., Khandare, J. J., & Calderón, M. (2015) · Chemical Society Reviews · doi:10.1039/c5cs00674k · Cited by 116 · see citing works
Regev-Shoshani, G., Ko, M., Miller, C., & Av‐Gay, Y. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00511-09 · Cited by 96 · see citing works
“sure chambers for direct topical application of NO (11, 20),”
BackgroundSelf-citationThe role of nanotechnology in combating biofilm-based antibiotic resistance
Malaekeh-Nikouei, B., Bazzaz, B. S. F., Mirhadi, E., Tajani, A., & Khameneh, B. (2020) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2020.101880 · Cited by 99 · see citing works
Poh, W. H., & Rice, S. A. (2022) · Molecules · doi:10.3390/molecules27030674 · Cited by 112 · see citing works
“evaluated the use of gaseous NO against various pathogens and its effect on human dermal fibroblasts in culture [62].”
BackgroundPark, J. H., Kumar, N., Park, D. H., Yusupov, M., Neyts, E., Verlackt, C., Bogaerts, A., Kang, M.-H., Uhm, H. S., Choi, E. H., et al. (2015) · Scientific Reports · doi:10.1038/srep13849 · Cited by 97 · see citing works
Bentur, L., Gur, M., Ashkenazi, M., Livnat-Levanon, G., Mizrahi, M., Tal, A., Ghaffari, A., Geffen, Y., Aviram, M., & Efrati, O. (2020) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2019.05.002 · Cited by 88 · see citing works
Self-citationDeupree, S. M., & Schoenfisch, M. (2009) · Acta Biomaterialia · doi:10.1016/j.actbio.2009.01.025 · Cited by 88 · see citing works
“Gaseous NO was found to be toxic against a number of pathogenic species, including Candida albicans and methacillin-resistant Staphylococcus aureus.(23) N-Diazeniumdiolate-modified NOreleasing surfaces have been shown to reduce initial Pseudomonas aeruginosa adhesion relative to controls,(24-26) and kill those that do…”
BackgroundElectrospun nitric oxide releasing bandage with enhanced wound healing.
Lowe, A., Bills, J. D., Verma, R., Lavery, L., Davis, K., & Balkus, K. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.11.032 · Cited by 86 · see citing works
Li, C., Li, H., Jiang, Z., Zhang, T., Wang, Y., Li, Z., Wu, Y., Ji, S., Xiao, S., Ryffel, B., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1003918 · Cited by 82 · see citing works
Seabra, A., Martins, D., Simões, M. M. S. G., da Silva, R., Brocchi, M., & de Oliveira, M. G. (2010) · Artificial Organs · doi:10.1111/j.1525-1594.2010.00998.x · Cited by 83 · see citing works
Neidrauer, M., Ercan, U. K., Bhattacharyya, A., Samuels, J., Sedlak, J., Trikha, R., Barbee, K., Weingarten, M., & Joshi, S. (2014) · Journal of Medical Microbiology · doi:10.1099/jmm.0.067322-0 · Cited by 82 · see citing works
Nanoparticles for the Treatment of Wounds.
Oyarzun-Ampuero, F. A., Vidal, A., Concha, M., Morales, J., Orellana, S., & Moreno‐Villoslada, I. (2015) · Current pharmaceutical design · doi:10.2174/1381612821666150901104601 · Cited by 81 · see citing works
Thi, T. T. H., Lee, Y., Thi, P. L., & Park, K. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.12.005 · Cited by 78 · see citing works
Park, D., Kim, J., Lee, Y. M., Park, J., & Kim, W. J. (2016) · Advanced Healthcare Materials · doi:10.1002/adhm.201600150 · Cited by 77 · see citing works
Malik, M. A., Jiang, C.-Q., Heller, R. S., Lane, J., Hughes, D., & Schoenbach, K. (2016) · doi:10.1016/j.cej.2015.07.092 · Cited by 75
Efficacy of gaseous nitric oxide in the treatment of skin and soft tissue infections
Ghaffari, A., Jalili, R., Ghaffari, M., Miller, C. C., & Ghahary, A. (2007) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2007.00239.x · Cited by 73 · see citing works
“Further support for diffusion capacity of gNO in an aqueous medium was provided by the significant sensitivity of bacterial cells exposed to the same level of gNO in previous studies.(14,15) Although the exact mechanism of tolerance to these levels of gNO is the subject of an ongoing study, it has been suggested that…”
BackgroundInfluentialSelf-citationWo, Y., Brisbois, E. J., Wu, J., Li, Z., Major, T. C., Mohammed, A., Wang, X., Colletta, A., Bull, J. L., Matzger, A. J., et al. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.6b00622 · Cited by 78 · see citing works
“Since NO is highly reactive in vivo and will be rapidly scavenged by surrounding species (e.g., oxyhemoglobin, oxygen), 55,56 to achieve therapeutic functions of NO, it is essential for the catheters to deliver localized NO release at their surface with minimal NO donor leaching.”
Nitric Oxide Releasing Nanoparticles for Treatment of Candida Albicans Burn Infections
Macherla, C., Sanchez, D. A., Ahmadi, M. S., Vellozzi, E. M., Friedman, A. J., Nosanchuk, J. D., & Martinez, L. R. (2012) · Frontiers in Microbiology · doi:10.3389/fmicb.2012.00193 · Cited by 70 · see citing works
“Ghaffari et al. (2006) has shown that NO is effective against C. albicans even though the fungus possesses a highly inducible NO defense mechanism (Ullmann et al., 2004; Tillmann et al., 2011).”
BackgroundMethodInfluentialHeilman, B. J., John, J. S., Oliver, S. R. J., & Mascharak, P. K. (2012) · Journal of the American Chemical Society · doi:10.1021/ja3022736 · Cited by 79 · see citing works
Hao, X., Mattson, A. M., Edelblute, C. M., Malik, M. A., Heller, L. C., & Kolb, J. F. (2014) · Plasma Processes and Polymers · doi:10.1002/ppap.201300187 · Cited by 74 · see citing works
Recent advances in nitric oxide delivery for antimicrobial applications using polymer-based systems
Sadrearhami, Z., Nguyen, T., Namivandi‐Zangeneh, R., Jung, K., Wong, E. H. H., & Boyer, C. A. (2018) · Journal of Materials Chemistry B · doi:10.1039/c8tb00299a · Cited by 136 · see citing works
Lu, Y., Slomberg, D., Sun, B., & Schoenfisch, M. (2013) · Small · doi:10.1002/smll.201201798 · Cited by 67 · see citing works
Current and emerging therapies in the management of diabetic foot ulcers
Karri, V. V. S. R., Kuppusamy, G., Talluri, S. V., Yamjala, K., Mannemala, S. S., & Malayandi, R. (2015) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1128888 · Cited by 74 · see citing works
Eroy‐Reveles, A. A., & Mascharak, P. K. (2009) · Future Medicinal Chemistry · doi:10.4155/fmc.09.111 · Cited by 75 · see citing works
Banch, T. J. H., Hanafiah, M., Alkarkhi, A., & Amr, S. A. A. (2019) · Polymers · doi:10.3390/polym11081349 · Cited by 62 · see citing works
“After settling, the efficacy of various tannin dosages at removing targeted parameters was determined [44].”
BackgroundMajor, T. A., Panmanee, W., Mortensen, J. E., Gray, L. D., Hoglen, N., & Hassett, D. J. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00379-10 · Cited by 61 · see citing works
“aeruginosa, and Candida albicans as both a topical agent (7) and as an inhalant in pulmonary infections (19).”
BackgroundDecreasing bacterial colonization of external fixation pins via nitric oxide release coatings
Holt, J., Hertzberg, B. P., Weinhold, P., Storm, W. L., Schoenfisch, M., & Dahners, L. (2011) · Journal of Orthopaedics and Trauma · doi:10.1097/bot.0b013e3181f9ac8a · Cited by 60 · see citing works
“Of importance, both Gram-positive and Gram-negative bacteria have been found to be susceptible to gaseous NO, including methicillin-resistant Staphylococcus aureus.(31) Members of our group have synthesized aminosilane-based xerogel films capable of storing large payloads of NO.”
On the Issues of NOx as Greenhouse Gases: An Ongoing Discussion…
Lasek, J. A., & Lajnert, R. (2022) · Applied Sciences · doi:10.3390/app122010429 · Cited by 66 · see citing works
Shi, Y.-T., Cao, Y., Cheng, J., Yu, W.-W., Liu, M., Yin, J., Huang, C.-S., Liang, X., Zhou, H., Liu, H., et al. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202111148 · Cited by 59
Suschek, C. V., & Opländer, C. (2016) · Clinical Plasma Medicine · doi:10.1016/j.cpme.2016.05.001 · Cited by 63 · see citing works
Miller, C. C., Hergott, C. A., Rohan, M., Arsenault-Mehta, K., Döring, G., & Mehta, S. (2013) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2013.01.008 · Cited by 54 · see citing works
“In vitro data suggest that higher concentrations of NO administration are directly bactericidal, while low levels of NO administration may exert antibacterial effects indirectly via stimulation of the host immune system [13].”
BackgroundSelf-citationJardeleza, C., Foreman, A., Baker, L. M., Paramasivan, S., Field, J., Tan, L., & Wormald, P. (2011) · International Forum of Allergy and Rhinology · doi:10.1002/alr.20083 · Cited by 54 · see citing works
Jones, M., Ganopolsky, J., Labbé, A., & Prakash, S. (2010) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-010-2490-x · Cited by 54 · see citing works
“A number of research groups have investigated use of gNO to kill bacteria and fungus in vitro; however, they have realized mixed results heavily dependent on the level of NO and duration of sustained release (Ghaffari et al. 2006; Hetrick et al. 2008, 2009).”
InfluentialSaini, V., Jain, V., Sudheesh, M., Jaganathan, K., Murthy, P. K., & Kohli, D. (2011) · International journal of pharmaceutics · doi:10.1016/j.ijpharm.2011.01.045 · Cited by 53
Privett, B., Deupree, S. M., Backlund, C. J., Rao, K. S., Johnson, C. B., Coneski, P. N., & Schoenfisch, M. (2010) · Molecular Pharmaceutics · doi:10.1021/mp100248e · Cited by 53 · see citing works
Regev-Shoshani, G., Ko, M., Crowe, A., & Av-Gay, Y. (2011) · Urology · doi:10.1016/j.urology.2011.02.063 · Cited by 50 · see citing works
Miller, C. C., Rawat, M., Johnson, T. L., & Av-Gay, Y. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00347-07 · Cited by 49 · see citing works
“We have shown that exogenous gaseous (gNO) is able to eradicate a variety of bacterial species including clinical isolates (6, 7, 12).”
BackgroundSelf-citationNitric oxide-releasing porous silicon nanoparticles
Kafshgari, M. H., Cavallaro, A., Delalat, B., Harding, F., McInnes, S. J. P., Mäkilä, E., Salonen, J., Vasilev, K., & Voelcker, N. (2014) · Nanoscale Research Letters · doi:10.1186/1556-276x-9-333 · Cited by 48 · see citing works
“NO is produced by various cells resident in the skin as one of the natural defenses of the immune system and should therefore prove to be effective against pathogen invasion while being tolerated by human skin [19].”
BackgroundHalpenny, G. M., Gandhi, K., & Mascharak, P. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml1000646 · Cited by 48 · see citing works
Gaseous nitric oxide reduces influenza infectivity in vitro
Regev-Shoshani, G., Vimalanathan, S., McMullin, B., Road, J., Av-Gay, Y., & Miller, C. C. (2013) · Nitric oxide · doi:10.1016/j.niox.2013.03.007 · Cited by 47 · see citing works
“Free NO or NO derived from donating compounds have been reported to exhibit antimicrobial activity during in vitro and in vivo animal studies [10] [11] [12] [13] .”
BackgroundSelf-citationSulemankhil, I., Ganopolsky, J. G., Dieni, C. A., Dan, A., Jones, M. L., & Prakash, S. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01173-12 · Cited by 55 · see citing works
“The gNO release rates correspond to releasing concentrations of above 200 ppmv, which was previously reported to have bactericidal activity against planktonic bacteria (18) (Fig.”
BackgroundInfluentialHalpenny, G. M., Steinhardt, R. C., Okialda, K., & Mascharak, P. (2009) · Journal of materials science. Materials in medicine · doi:10.1007/s10856-009-3795-0 · Cited by 47 · see citing works
Adnan, N. N. M., Sadrearhami, Z., Bagheri, A., Nguyen, T.-K., Wong, E., Ho, K., Lim, M., Kumar, N., & Boyer, C. (2018) · Macromolecular rapid communications · doi:10.1002/marc.201800159 · Cited by 46
Light-triggered nitric oxide delivery to malignant sites and infection
Heilman, B. J., & Mascharak, P. K. (2013) · Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences · doi:10.1098/rsta.2012.0368 · Cited by 48 · see citing works
“Although delivery of gaseous NO directly to infected wounds has shown promise [58,59], handling of this noxious and highly diffusible gas in a hospital setting presents a discouraging task in general.”
BackgroundSilva, S. Y., Rueda, L. C., Márquez, G., López, M., Smith, D. J., Calderón, C. A., Castillo, J., Matute, J., Rueda-Clausen, C., Orduz, A., et al. (2007) · Trials · doi:10.1186/1745-6215-8-26 · Cited by 46 · see citing works
“It has been described that NO stimulates collagen synthesis [48], triggers the release of chemotactic cytokines [49], and has an important microbicidal effect by interfering with the enzymatic processes of the bacterial mitochondrial respiratory chain [50].”
BackgroundPrivett, B. J., Nutz, S. T., & Schoenfisch, M. H. (2010) · Biofouling · doi:10.1080/08927014.2010.534552 · Cited by 45 · see citing works
“Indeed, sustaining effective NO levels for a given application has proven most challenging (Ghaffari et al. 2006).”
BackgroundCisneros, C. G., Bloemen, V., & Mignon, A. (2021) · Polymers · doi:10.3390/polym13050760 · Cited by 45 · see citing works
“There is a delay of hours for the production of NO• due to the time for protein synthesis, but the reached NO• concentration is higher and sustains for as long as the enzyme is present [10,15,19].”
BackgroundNitric Oxide Therapy for Dermatologic Disease
Adler, B. L., & Friedman, A. J. (2015) · Future Science OA · doi:10.4155/fso.15.37 · Cited by 43 · see citing works
Ahmadi, M. S., Lee, H. H., Sanchez, D. A., Friedman, A. J., Tar, M. T., Davies, K. P., Nosanchuk, J. D., & Martinez, L. R. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02659-15 · Cited by 41 · see citing works
“albicans despite the fungus’s inherent (17, 18), inducible NO defense mechanism (19).”
BackgroundSrisuwan, S., Tongtawe, P., Srimanote, P., & Voravuthikunchai, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110321 · Cited by 41 · see citing works
“iNOS expression results in the production of NO which reduces the viability of Gram-positive and Gram-negative bacteria, especially intracellular bacteria [37,38].”
BackgroundThe antimicrobial effects of nitric oxide: A narrative review
Okda, M. M., Spina, S., Fakhr, B. S., & Carroll, R. W. (2025) · Nitric Oxide · doi:10.1016/j.niox.2025.01.001 · Cited by 44 · see citing works
Eby, G. A. (2006) · Medical Hypotheses · doi:10.1016/j.mehy.2005.11.035 · Cited by 38 · see citing works
Therapeutic Effects of Inhaled Nitric Oxide Therapy in COVID-19 Patients
Олегович, К. Н., Berra, L. M., & Carroll, R. W. (2022) · Biomedicines · doi:10.3390/biomedicines10020369 · Cited by 40 · see citing works
Antibacterial properties of nitric oxide-releasing porous silicon nanoparticles.
Kafshgari, M. H., Delalat, B., Harding, F., Cavallaro, A., Mäkilä, E., Salonen, J., Vasilev, K., & Voelcker, N. (2016) · Journal of materials chemistry. B · doi:10.1039/c5tb02551f · Cited by 36 · see citing works
Ormerod, A., Shah, A., Li, H., Benjamin, N., Ferguson, G. P., & Leifert, C. (2011) · BMC Research Notes · doi:10.1186/1756-0500-4-458 · Cited by 36 · see citing works
Sun, Y., Liu, Y., Liu, W., Lu, C., & Lei, W. (2015) · Biochemical Engineering Journal · doi:10.1016/j.bej.2014.11.022 · Cited by 35 · see citing works
Chitosan chemically modified to deliver nitric oxide with high antibacterial activity.
Pelegrino, M. T., Pieretti, J. C., Nakazato, G., Gonçalves, M. C., Moreira, J., & Seabra, A. (2020) · Nitric oxide · doi:10.1016/j.niox.2020.10.003 · Cited by 34 · see citing works
Allan, R., Morgan, S., Brito-Mutunayagam, S., Skipp, P., Feelisch, M., Hayes, S., Hellier, W. B., Clarke, S., Stoodley, P., Burgess, A., et al. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02432-15 · Cited by 34 · see citing works
Use of nanoparticles as therapy for methicillin-resistant Staphylococcus aureus infections.
Liu, P., Lo, C.-W., Chen, C.-H., Hsieh, M.-F., & Huang, C.-M. (2009) · Current drug metabolism · doi:10.2174/138920009790274522 · Cited by 34 · see citing works
“It is reported that 200 ppm gaseous NO can kill Grampositive/negative bacteria, including Staphylococcus aureus and is nontoxic to human dermal fibroblasts [146].”
BackgroundRajoo, A., Ramanathan, S., Mansor, S., & Sasidharan, S. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.113414 · Cited by 33
Zhang, Z., Wang, J., Chai, R.-Y., Qiu, H.-P., Jiang, H., Mao, X.-Q., Wang, Y.-L., Liu, F.-Q., & Sun, G. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120627 · Cited by 33
Verma, R., Singh, A., Mohan, M., Agrawal, A., Verma, P., Gupta, A., & Misra, A. (2012) · Molecular Pharmaceutics · doi:10.1021/mp300269g · Cited by 33
Biomedical evaluation of a novel nitrogen oxides releasing wound dressing
Dave, R. N., Joshi, H. M., & Venugopalan, V. (2012) · Journal of materials science. Materials in medicine · doi:10.1007/s10856-012-4766-4 · Cited by 33 · see citing works
“Emergence of resistant bacterial strains and relatively avascular nature of the wounds make them particularly difficult to manage by systemic drug administration [7].”
BackgroundAntibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease
Bogdanovski, K., Chau, T., Robinson, C. J., MacDonald, S. D., Peterson, A. M., Mashek, C. M., Wallin, W. A., Rimkus, M., Montgomery, F., da Silva, J. L., et al. (2020) · Access Microbiology · doi:10.1099/acmi.0.000154 · Cited by 35 · see citing works
“Based on previous preclinical and clinical studies [18–22], the planned treatment for course 1 was 160 p.p.m. inhaled NO for 30 min every 3–4 h daily (five times/day) for 1–14 days followed by three times per day for days 15–21 (Fig.”
Self-citationBang, C. S., Kinnunen, A., Karlsson, M., Önnberg, A., Söderquist, B., & Persson, K. (2014) · BMC Microbiology · doi:10.1186/1471-2180-14-65 · Cited by 31 · see citing works
“In contrast to antibiotics that are specific to one or few bacterial species, the antibacterial effects of NO are broad and both gram-positive and gramnegative pathogens, including antibiotic-resistant isolates show sensitivity [40,41].”
BackgroundInvestigation of probiotic bacteria as dental caries and periodontal disease biotherapeutics.
Saha, S., Tomaro-Duchesneau, C., Rodes, L., Malhotra, M., Tabrizian, M., & Prakash, S. (2014) · Beneficial Microbes · doi:10.3920/bm2014.0011 · Cited by 31 · see citing works
“NO is known both for its antibacterial (Ghaffari et al., 2006) and anti-inflammatory properties (Lamine et al.”
BackgroundFrom Autonomous Chemical Micro‐/Nanomotors to Rationally Engineered Bio‐Interfaces
Ding, M., Chen, B., Wilson, D. A., Tu, Y., & Peng, F. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202423207 · Cited by 24 · see citing works
Roles and current applications of S-nitrosoglutathione in anti-infective biomaterials
Hu, Q., Ye, Z., Pi, L., & Ao, J. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100419 · Cited by 25 · see citing works
“In the early 1990s, the critical role of NO in combating pathogen infection was reported for the first time [111,149].”
BackgroundRoutier, A., Blaizot, A., Agossa, K., & Dubar, M. (2021) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2021.105196 · Cited by 30 · see citing works
“This substance is known for its bactericidal activity against a wide range of bacteria, including anaerobic bacteria such as P. gingivalis and F. nucleatum ( Allaker et al., 2001; Ghaffari et al ., 2006).”
BackgroundStasko, N., McHale, K. A., Hollenbach, S. J., Martin, M., & Doxey, R. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01026-17 · Cited by 42 · see citing works
Devine, R., Douglass, M. E., Ashcraft, M. M., Tayag, N., & Handa, H. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c01330 · Cited by 32 · see citing works
Tar, M., Cabrales, P., Mahantesh, N., Adler, B., Nacharaju, P., Friedman, A., Friedman, J., & Davies, K. (2014) · Journal of Sexual Medicine · doi:10.1111/jsm.12705 · Cited by 29 · see citing works
“Several technologies have been proposed for cutaneous delivery of NO, including but not limited to, compressed gas cylinders that deliver NO directly to wounds [36], acidified nitrite cream that release NO [37] and diazeniumdiolates [38] that give off NO spontaneously from a donor compound.”
Background
- Authors
- Ghaffari, A., Miller, C. C., McMullin, B., & Ghahary, A.
- Affiliations
- University of British Columbia (CA)
- University of British Columbia Hospital (CA)
- Corresponding author
- Ghaffari, A.
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 14
- Issue
- 1
- Pages
- 21-29
- ISSN
- 1089-8603 (ISSN-L)
- OpenAlex
- W2131902476
- Cited by
- 236
- References
- 0
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 8 · 2023: 11 · 2022: 18 · 2021: 10 · 2020: 13 · 2019: 10 · 2018: 16 · 2017: 12 · 2016: 15 · 2015: 11 · 2014: 19 · 2013: 13 · 2012: 14
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nitric Oxide (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Università degli Studi di Camerino
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Plasma Applications and Diagnostics
- Keywords
- topical antimicrobial therapy, wound infection, burns, chronic ulcers, antibacterial activity, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus agalactiae, Escherichia coli, Candida albicans, dermal fibroblasts, cytotoxicity, extracellular matrix gene expression, MMP-1, type I procollagen, wound healing
- MeSH terms
- Administration, Topical, Anti-Infective Agents, Cells, Cultured, Culture Media, Extracellular Matrix, Fibroblasts, Gases, Humans, Microbial Sensitivity Tests, Nitric Oxide, Skin
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