Effects of indomethacin on erythrocyte nitric oxide metabolism and erythrocyte deformability

Article Sidebar

PDF Download
Published Apr 17, 2018
DOI: https://doi.org/10.18103/mra.v6i4.1737

Downloads

Download data is not yet available.

Submit your own article

Register as an author to reserve your spot in the next issue of the Medical Research Archives.

Author Registration

Join the Society

The European Society of Medicine is more than a professional association. We are a community. Our members work in countries across the globe, yet are united by a common goal: to promote health and health equity, around the world.

Join Europe’s leading medical society and discover the many advantages of membership, including free article publication.

Membership

Main Article Content

Carlota Saldanha
Universidade de Lisboa, Lisbon, Portugal
Teresa Freitas
Universidade de Lisboa, Lisbon, Portugal
Stephen Cook
East London Eye Centre; Walter Sisulu University and Frere Hospital South Africa
Ana Santos Silva-Herdade
Universidade de Lisboa, Lisbon, Portugal

Abstract

Increased erythrocyte filtration index (decreased erythrocyte deformability; ED) was observed in patients with Behçet disease. When patients with Behçet took indomethacin, decreased values of erythrocyte acetylcholinesterase enzyme activity were obtained. An inverse association between nitric oxide (NO) efflux from erythrocytes and ED values was verified in blood samples of patients with vascular inflammatory diseases.


The aim of this in vitro study was to verify the effect of indomethacin on ED, NO efflux, nitrite nitrate, peroxynitrite and nitroso- glutathione (GSNO) in  the presence of protein tyrosine kinase (PTK Syk), protein tyrosine phosphatase (PTP),  adenylyl cyclase (AC) and phosphatidylinositol 3 kinase (PI3K) enzyme  inhibitors respectively Syk inhibitor, calpeptin, MDL and wortmannin (WORT).  Blood samples from ten healthy donors were divided and aliquots were performed in absence (control aliquot) and presence of indomethacin or indomethacin plus each one of the inhibitors. Further ED and NO efflux and its metabolites were evaluated by the usual methodology.


A significant increase in ED values was noted in the presence of indomethacin plus WORT.  No significant differences where verified in NO efflux from erythrocytes in all blood aliquots. Significantly increase in GSNO concentration in the presence of indomethacin plus calpeptin, MDL or Wort were observed.  Nitrate and peroxynitrite concentrations increased or decreased significantly respectively in all aliquots in relation to the control one. The nitrite levels increased in the aliquots with indomethacin and indomethacin plus MDL, or indomethacin plus Syk.


In conclusion indomethacin act as antioxidant decreasing peroxynitrite, not changing NO efflux values and increasing nitrate levels independent of band 3 phosphorylation degree or cyclic adenosine monophosphate (cAMP) concentration. Indomethacin mobilizes nitrite and GSNO in dependant of band 3 phosphorylation degree and cAMP. Indomethacin did not change erythrocyte deformability, unless in combination with wortmannin which increased it.

Keywords: Indomethacin, erythrocyte deformability, nitric oxide, antioxidant

Article Details

How to Cite
SALDANHA, Carlota et al. Effects of indomethacin on erythrocyte nitric oxide metabolism and erythrocyte deformability. Medical Research Archives, [S.l.], v. 6, n. 4, apr. 2018. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1737>. Date accessed: 21 dec. 2024. doi: https://doi.org/10.18103/mra.v6i4.1737.
ABNT APA BibTeX CBE EndNote - EndNote format (Macintosh & Windows) MLA ProCite - RIS format (Macintosh & Windows) RefWorks Reference Manager - RIS format (Windows only) Turabian
Issue
Vol 6 No 4 (2018): Vol.6 Issue 4 April 2018
Section
Research Articles

The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.

 

References

1. Zhou Y, Hancock JF, Lichtenberger LM. The Nonsteroidal Anti-Inflammatory Drug Indomethacin Induces Heterogeneity in Lipid Membranes: Potential Implication for Its Diverse Biological Action. PLoS ONE 2010; 5(1): e8811. doi:10.1371/journal. pone.0008811
2. Spink CH, Yeager MD, Feigenson GW Partitioning behavior of indocarbocyanine probes between coexisting gel and fluid phases in model membranes. Biochim Biophys Acta 1990; 21023: 25–3.
3 Zhou Y, Plowman SJ, Lichtenberger LM, Hancock JF. The anti-inflammatory drug indomethacin alters nanoclustering in synthetic and cell plasma membranes. J Biol Chem 2010; 285(45): 35188-35195.
4. Nwafor A, Coakley WT. The effect of membrane diffusion potential change on anionic drugs indomethacin and barbitoneinduced human red blood cell shape change and cellular uptake of drugs. African J of Biomed Res 2003; 6:95-100.
5 de Souza-Ramalho P, Santos MD, Martins R, Freitas JP, Cardoso L, Pinto J, Saldanha C, Martins-Silva J. Hemorheolo-gical changes in Behçet`s disease. Rev. Port. Hemorrreol 1987; 1: 89-94
6. Saldanha C. Human erythrocyte acetylcholinesterase in health and disease. Molecules 2017; 22(9): pii: E1499. DOI: 10.3390/molecules22091499
7 Saldanha C, Silva-Herdade AS. Erythrocyte acetylcholinesterase is a sugnaling receptor. Nov Appro Drug Res Dev 2018; 3(4): NAPDD.MS.ID.555617 (2018) DOI: 0.10.19080/NAPDD.2018.03. 5556\7
8. Carvalho FA, de Almeida JP, Freitas-Santos T, Saldanha C. Modulation of erythrocyte acetylcholinesterase activity and its association with G protein-band 3 interactions. J Membr Biol 2009; 228(2):89-97.
9. Teixeira P, Duro N, Napoleão P, Saldanha C. Acetylcholinesterase Conformational States Influence Nitric Oxide Mobilization in the Erythrocyte. J Membrane Biol 2015; 248: 349-354.
10. Brunati AM, Bordin L, Clari G, James P, Quadroni M, Baritono E, Pinna LA and Donella-Deana A. Sequential phosphorylation of protein band 3 by Syk and Lyn tyrosine kinases in intact human erythrocytes: identification of primary and secondary phosphorylation sites. Blood 2000; 96: 1550–1557.
11. Jia L, Bonaventura C, Bonaventura J, Stamler JS. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 1996; 380: 221-226. DOI: 10.1038/380221a0
12. Pawloski JR, Hess DT, Stamler JS. Export by red blood cells of nitric oxide bioactivity. Nature 2001; 409: 622–626. DOI:10.1038/35054560
13. Mesquita R, Pires I, Saldanha C, Martins e Silva J. Effects of acetylcholine and SpermineNONOate on erythrocyte hemorheologic and oxygen carrying properties. Clin Hemorheol Microcirc 2001; 25: 153-163.
14. Carvalho FA, Maria AV, Guerra J, Moreira C, Braz-Nogueira J, Martins e Silva J, Saldanha C. The relation between the erythrocyte nitric oxide and hemorheological parameters. Clin Hemorheol Microcirc 2006; 35: 341-347.
15. Carvalho FA, Martins-Silva J, Saldanha C. Amperometric measurements of nitric oxide in erythrocytes. Biosens Bioelectron 2004; 20: 505–508.
16. Guevara I, Iwanejko J, Dembińska-Kieć A, Pankiewicz J, Wanat A, Anna P, Gołabek I, Bartus S, Malczewska-Malec M, Szczudlik A. Determination of nitrite/nitrate in human biological material by the simple Griess reaction. Clin Chim Acta 1998; 274: 177-188.
17. Carvalho FA, Mesquita R, Martins-Silva J, Saldanha C. Acetylcholine and choline effects on erythrocyte nitrite and nitrate levels. J Appl Toxicol 2004; 24: 419–427.
18. Cook JA, Kim SY, Teague D, Krishna MC, Pacelli R, Mitchell JB, Vodovotz Y, Nims RW, Christodoulou D, Miles AM, Grisham MB, Wink DA. Convenient colorimetric and fluorometric assays for S-nitrosothiols. Anal Biochem 1996; 238: 150-158.
19.Possel H, Noack H, Augustin W, Keilhoff G, Wolf G. 2,7-dichlorofluor-escein diacetate as a fluorescent marker for peroxinitrite formation. FEBS Letters 1997; 416: 175-178.
20. Saldanha C, Lopes de Almeida JP, Freitas T, de Oliveira S, Silva-Herdade AS. Erythrocyte deformability responses to shear stress under external and internal Influences. Series on Biomechanics 2010; 25: 54-60.
21. Saldanha, A. S. Silva, S. Gonçalves, J. Martins e Silva Modulation of erythrocyte hemorheological properties by band 3 phosphorylation and dephosphorylation. Clin Hemorhreol Microcir2006; 36:183-194.
22. Shakur Y, Holst LS, Landstrom TR, Movsesian M, Degerman E, Manganiello V. Regulation and function of the cyclic nucleotide phosphodiesterase (PDE3) gene family. Prog Nucleic Acid Res Mol Biol 2001; 66: 241–277.
23. Hanson MS Stephenson AH, Bowles EA, Sridharan M, Adderley S, Sprague RS. Phosphodiesterase 3 is present in rabbit and human erythrocytes and its inhibition potentiates iloprost-induced increases in cAMP. Am J Physiol Heart Circ Physiol 2008; 295: H786–H793.
24. Jindal H, Ai KZ Gascard P, Horton C, Cohen CM. Specific Loss of Protein Kinase Activities in Senescent Erythrocytes. Blood 1996; 88: 1479-1487.
25. Balagopalakrishna C, Manoharan PT, Abugo OO, Rifkind JM. Production of superoxide from hemoglobin-bound oxygen under hypoxic conditions. Biochemistry 1996; 35:6393–6398. DOI: 10.1021/ bi952875.
26. Schabbauer G, Tencati M, Pedersen B, Pawlinski R, Mackman N. PI3K-Akt pathway suppresses coagulation and inflammation in endotoxemic mice. Arterioscler Thromb Vasc Biol 2004; 24: 1963-1969.
27. Bütikofer P, Brodbeck U, Ott P. Modulation of erythrocyte vesiculation by amphiphilic drugs. Biochim Biophys Acta 1987; 901(2): 291-295.
28. Kostova EB, Beuger BM, Klei TRL, HalonenP, Lieftink C, Beijersbergen R, van den Berg TK and van Bruggen R. Identification of signalling cascades involved in red blood cell shrinkage and vesiculation. Biosci Rep 2015; 35(2): pii:e00187. doi 10.1042/BSR20150019
29. Gladwin MT, Wang X, Reiter CD. Snitrosohemoglobin is unstable in the reductive erythrocyte environment and lacks O2/NO-linked allosteric function. J Biol Chem 2002; 277: 27818–27828. DOI: 10.1074/jbc.M203236200.
30. Carvalho FA, Mesquita R, Martins-Silva J, Saldanha C. Acetylcholine and choline effects on erythrocyte nitrite and nitrate levels. J Appl Toxicol 2004; 24: 419-427. DOI: 10.1002/jat.993
31. Inal ME, Egüz AM. The effects of isosorbide dinitrate on methemoglobin reductase enzyme activity and antioxidant states. Cell Biochem Funct 2004; 22: 129–133. DOI: 10.1002/cbf.1007.