The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
High-dose oral N -acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis
Abstract
Neutrophilic airway inflammation is a hallmark of cystic fibrosis (CF). As high oxidant producers, airway neutrophils contribute largely to the systemic redox imbalance seen in CF. In turn, this chronic and profound imbalance can impact circulating neutrophils before their migration into airways. Indeed, in 18 CF patients with stable disease, blood neutrophils were readily deficient in the pivotal antioxidant glutathione ( P = 0.003, compared with 9 healthy controls). In a phase 1 study, this deficiency was improved ( P = 0.025) by the glutathione prodrug N -acetylcysteine, given orally in high doses (0.6 to 1.0 g three times daily, for 4 weeks). This treatment was safe and markedly decreased sputum elastase activity ( P = 0.006), the strongest predictor of CF pulmonary function. Consistently, neutrophil burden in CF airways was decreased upon treatment ( P = 0.003), as was the number of airway neutrophils actively releasing elastase-rich granules ( P = 0.005), as measured by flow cytometry. Pulmonary function measures were not improved, as expected with short-term treatment. After excluding data from subjects without baseline airway inflammation, positive treatment effects were more pronounced and included decreased sputum IL-8 levels ( P = 0.032). Thus, high-dose oral N -acetylcysteine has the potential to counter the intertwined redox and inflammatory imbalances in CF.
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Cited by
Glutathione dysregulation and the etiology and progression of human diseases
Ballatori, N., Krance, S. M., Notenboom, S., Shi, S., Tieu, K., & Hammond, C. L. (2009) · bchm · doi:10.1515/bc.2009.033 · Cited by 1,114
N-Acetylcysteine—a safe antidote for cysteine/glutathione deficiency
Atkuri, K. R., Mantovani, J. J., Herzenberg, L. A., & Herzenberg, L. A. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.04.005 · Cited by 721
Self-citationRushworth, G. F., & Megson, I. L. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.09.006 · Cited by 719
N-Acetylcysteine (NAC): Impacts on Human Health
Tenório, M. C. D. S., Graciliano, N. G., Moura, F. A., Oliveira, A. C. M. D., & Goulart, M. O. F. (2021) · Antioxidants · doi:10.3390/antiox10060967 · Cited by 526
Applying insights from biofilm biology to drug development — can a new approach be developed?
Bjarnsholt, T., Ciofu, O., Molin, S., Givskov, M., & Høiby, N. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4000 · Cited by 516
Metadata
- Authors
- Tirouvanziam, R., Conrad, C. K., Bottiglieri, T., Herzenberg, L. A., Moss, R. B., & Herzenberg, L. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-03-13
- Volume
- 103
- Issue
- 12
- Pages
- 4628-4633
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1967713626
- Cited by
- 253
- References
- 35
- FWCI
- 18.25
- Type
- journal article
- Language
- en
- Open access
- closed
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- Tirouvanziam, R., Conrad, C. K., Bottiglieri, T., Herzenberg, L. A., Moss, R. B., & Herzenberg, L. A. (2006). High-dose oral N -acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0511304103
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