Suppression of Oxidative Stress as a Mechanism of Reduction of Hypercholesterolemic Atherosclerosis by Cyclooxygenase Inhibitors
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Notice bibliographique
Résumé
Hypercholesterolemia increases the formation of arachidonic acid from membrane phospholipids. Reactive oxgyen species (ROS) are generated during the synthesis of prostaglandins (PGs) from arachidonic acid. ROS have been implicated in the development of hypercholesterolemic atherosclerosis. Inhibition of the synthesis of PGs by indomethacin or naproxen, therefore, should be able to prevent the generation of ROS and hence the development of atherosclerosis. The objective of this study was to determine if indomethacin or naproxen reduces the development of hypercholesterolemic atherosclerosis and if this reduction is associated with decrease in the oxidative stress. Rabbits were assigned to 5 groups: Group I, control; Group II, indomethacin control (6 mg·kg body wt−1·d−1 PO); Group III, 0.5% cholesterol; Group IV, 0.5% cholesterol plus indomethacin (6 mg·kg body wt−1·d−1 PO); Group V, 0.5% cholesterol plus naproxen (10 mg·kg body wt−1·d−1 PO). Blood samples were collected before (time 0) and after 1 and 2 months of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), LDL and HDL cholesterol (LDL-C, HDL-C), serum malondialdehyde (MDA), and white blood cell chemiluminescence (WBC-CL), a measure of ROS produced by WBC. At the end of the protocol, the aorta was removed for measurement of atherosclerotic plaques, MDA, an aortic tissue lipid peroxidation product, and aortic tissue chemiluminescence (Aortic-CL), a marker of antioxidant reserve. Serum TG, LDL-C, HDL-C and the ratio TC/HDL-C increased to a similar extent in Groups III, IV and V at months 1 and 2 compared with time 0. Indomethacin and naproxen had practically no effect on serum lipid levels. Serum MDA increased to a similar extent in Groups III and IV and to a greater extent in Group V compared with 0 time. WBC-CL activity was similar in the 5 groups. There was an increase in the levels of aortic-MDA in Groups III and IV as compared to Group I or II, the increase being smaller in Group IV than in Group III. Aortic MDA values in Group V were lower than those in all other groups. Antioxidant reserve increased in Groups III and V but remained unchanged in Group IV compared to Groups I or II. Indomethacin and naproxen reduced hypercholesterolemic atherosclerosis by 46.73% and 46.56%, respectively. Indomethacin and naproxen, the inhibitors of prostaglandin synthesis, reduced hypercholesterolemic atherosclerosis and this effect was associated with a decrease in the oxidative stress. These results suggest that ROS generated during synthesis of prostaglandins in hypercholesterolemia might in part contribute to the development of hypercholesterolemic atherosclerosis.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle