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Analytical Techniques for Assaying Nitric Oxide Bioactivity
Published on: June 18, 2012
Evaluation of possible effects of crocin against nitrate tolerance and endothelial dysfunction
Seyedeh Farzaneh Omidkhoda1, BiBi Marjan Razavi2,1, Mohsen Imenshahidi1
1Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Objectives:
One of the most important problems of taking nitroglycerin is the nitrate tolerance phenomenon and endothelial dysfunction. Oxidative stress is a high-emphasized one of tolerance mechanisms. The possible effect of crocin, one of the anti-oxidant ingredients of saffron, on the nitrate tolerance model was investigated.
Materials And Methods:
In the present study, lipid peroxidation and the level of activated and deactivated forms of eNOS were measured. Animals were administered subcutaneously with 25 mg/kg of nitroglycerin, twice a day for 3 days to induce nitrate tolerance model. For evaluation of crocin effects, 20, 40 and 80 mg/kg/day of this compound were injected intraperitoneally in concomitant with nitroglycerin. In the isolated aorta test, after preparation of aorta rings, different concentrations of acetylcholine, sodium nitroprusside and nitroglycerin were added to the organ bath after inducing contraction by phenylephrine and the responsiveness of tissues was recorded.
Results:
Findings showed that nitroglycerin administration caused a remarkable overproduction of malondialdehyde (MDA) in the cells and crocin treatment significantly decreased the MDA level. In the nitrate tolerance group, the level of activated eNOS decreased and the level of deactivated eNOS increased. Crocin partly alleviated these changes: however, its effects were not remarkable. Nitroglycerin injection for 3 days developed tolerance to nitroglycerin and cross-tolerance to acetylcholine (endothelial dysfunction) and sodium nitroprusside. Crocin failed to influence significantly on the nitrate tolerance.
Conclusion:
Crocin effectiveness is possibly time-dependent; therefore, increasing the duration of treatment with crocin may lead to a significant prevention of nitrate tolerance and endothelial dysfunction.
Insights
Crocin, an antioxidant from saffron, did not significantly prevent nitrate tolerance or endothelial dysfunction in a 3-day animal model. Further research is needed to explore crocin
Area of Science:
- Pharmacology
- Cardiovascular Research
- Oxidative Stress
Background:
- Nitroglycerin is crucial for treating cardiovascular conditions but can lead to nitrate tolerance and endothelial dysfunction.
- Oxidative stress is a key mechanism contributing to the development of nitrate tolerance.
- Crocin, a potent antioxidant found in saffron, is investigated for its potential therapeutic effects.
Purpose of the Study:
- To investigate the effect of crocin on a rat model of nitrate tolerance and associated endothelial dysfunction.
- To assess crocin's impact on oxidative stress markers and endothelial nitric oxide synthase (eNOS) activity.
- To determine if crocin can mitigate tolerance to nitroglycerin and cross-tolerance to acetylcholine and sodium nitroprusside.
Main Methods:
- Nitrate tolerance was induced in rats via subcutaneous nitroglycerin administration.
- Crocin was administered intraperitoneally at varying doses alongside nitroglycerin.
- Lipid peroxidation (MDA levels), eNOS activation status, and aortic tissue responsiveness were measured.
Main Results:
- Nitroglycerin induced significant oxidative stress, evidenced by increased malondialdehyde (MDA) levels, which crocin partially reduced.
- Nitroglycerin treatment led to decreased activated eNOS and increased deactivated eNOS, with crocin showing only minor alleviation.
- The model developed tolerance to nitroglycerin and cross-tolerance to acetylcholine and sodium nitroprusside, which crocin did not significantly impact.
Conclusions:
- Crocin demonstrated a limited effect in preventing short-term nitrate tolerance and endothelial dysfunction in this model.
- The study suggests that crocin's effectiveness might be time-dependent, requiring longer treatment durations for potential benefits.
- Further investigation into prolonged crocin administration is warranted to fully evaluate its therapeutic potential against nitrate tolerance.
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