Cited by 242Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Comparative pharmacology of chemically distinct nadph oxidase inhibitors

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Wind, S, Beuerlein, K, Eucker, T, Müller, H, Scheurer, P, Armitage, ME, Ho, H, Schmidt, HHHW +1 more·2010·British Journal of Pharmacology

Abstract

BACKGROUND AND PURPOSE Oxidative stress [i.e. increased levels of reactive oxygen species (ROS)] has been suggested as a pathomechanism of different diseases, although the disease‐relevant sources of ROS remain to be identified. One of these sources may be NADPH oxidases. However, due to increasing concerns about the specificity of the compounds commonly used as NADPH oxidase inhibitors, data obtained with these compounds may have to be re‐interpreted. EXPERIMENTAL APPROACH We compared the pharmacological profiles of the commonly used NADPH oxidase inhibitors, diphenylene iodonium (DPI), apocynin and 4‐(2‐amino‐ethyl)‐benzolsulphonyl‐fluoride (AEBSF), as well as the novel triazolo pyrimidine VAS3947. We used several assays for detecting cellular and tissue ROS, as none of them is specific and artefact free. KEY RESULTS DPI abolished NADPH oxidase‐mediated ROS formation, but also inhibited other flavo‐enzymes such as NO synthase (NOS) and xanthine oxidase (XOD). Apocynin interfered with ROS detection and varied considerably in efficacy and potency, as did AEBSF. Conversely, the novel NADPH oxidase inhibitor, VAS3947, consistently inhibited NADPH oxidase activity in low micromolar concentrations, and interfered neither with ROS detection nor with XOD or eNOS activities. VAS3947 attenuated ROS formation in aortas of spontaneously hypertensive rats (SHRs), where NOS or XOD inhibitors were without effect. CONCLUSIONS AND IMPLICATIONS Our data suggest that triazolo pyrimidines such as VAS3947 are specific NADPH oxidase inhibitors, while DPI and apocynin can no longer be recommended. Based on the effects of VAS3947, NADPH oxidases appear to be a major source of ROS in aortas of SHRs.

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Authors
Wind, S., Beuerlein, K., Eucker, T., Müller, H., Scheurer, P., Armitage, M., Ho, H., Schmidt, H., & Wingler, K.
Affiliations
  • Justus-Liebig-Universität Gießen (DE)
  • Vasopharm (Germany) (DE)
  • Florey Institute of Neuroscience and Mental Health (AU)
ORCID
Wind, S
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2010-06-17
Volume
161
Issue
4
Pages
885-898
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
OpenAlex
W1736337862
Cited by
241
References
50
Citations by year
2026: 3 · 2025: 6 · 2024: 5 · 2023: 13 · 2022: 8 · 2021: 10 · 2020: 12 · 2019: 7 · 2018: 13 · 2017: 16 · 2016: 23 · 2015: 23 · 2014: 28 · 2013: 29 · 2012: 31
FWCI
16.03
Type
journal article
Language
en
Open access
Locations
  • British Journal of Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
  • Deutsche Forschungsgemeinschaft (SFB-547)
  • Bayerische Forschungsstiftung
  • Medical Research Council
  • National Health and Medical Research Council
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
NADPH oxidase inhibitors, reactive oxygen species, oxidative stress, diphenyleneiodonium, apocynin, AEBSF, xanthine oxidase inhibition, eNOS inhibition, spontaneously hypertensive rats, aorta
MeSH terms
Acetophenones, Animals, Aorta, Cell Line, Enzyme Inhibitors, Humans, Onium Compounds, Pyrimidines, Rats, Inbred SHR, Rats, Inbred WKY, Sulfones, Triazoles, Reactive Oxygen Species, Oxidative Stress, HL-60 Cells, Caco-2 Cells, NADPH Oxidases, Rats

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