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Modulation of nitric oxide synthase activity by ibuprofen
1Institute of Immunology, University of Vienna Scientific Research Center Baden, Austria.
Inflammation
|August 1, 1997
Summary
Ibuprofen activates both inflammatory and normal nitric oxide synthase (NOS) enzymes, and increases NO production at high doses. It is not suitable for selective iNOS inhibition in treating inflammation.
Area of Science:
- Biochemistry
- Pharmacology
- Immunology
Background:
- Nitric oxide (NO) synthesis inhibition is a novel therapeutic strategy for inflammation.
- Selective inhibition of inducible nitric oxide synthase (iNOS) is crucial to avoid cardiovascular side effects from inhibiting constitutive endothelial NOS (cNOS).
Purpose of the Study:
- To investigate the effects of ibuprofen and its stereoisomers on iNOS and cNOS activation.
- To assess the impact of ibuprofen on NO production in human umbilical vein endothelial cells.
Main Methods:
- Enzyme activity assays for iNOS and cNOS.
- Measurement of NO production in endothelial cell cultures.
- Evaluation of ibuprofen's stereoisomers.
Main Results:
- Ibuprofen activated iNOS and inhibited cNOS at therapeutic concentrations.
- Elevated NO production was observed with supratherapeutic ibuprofen concentrations.
- Both stereoisomers of ibuprofen exhibited similar effects.
Conclusions:
- Ibuprofen is not a selective iNOS inhibitor.
- The non-selective action of ibuprofen limits its therapeutic potential for inflammation via NOS inhibition.