Cardioprotective effects of the flavonoid quercetin against doxorubicin-Induced cardiotoxicity in H9c2 cardiomyoblasts
Notice bibliographique
Résumé
Abstract Background Doxorubicin (DOX) is an effective chemotherapy drug to treat diverse cancers such as breast, ovarian, small cell lung, and leukaemia. However, its use is limited by dose-dependent cardiotoxicity, leading to conditions such as cardiac arrhythmias, cardiomyopathy, and congestive heart failure. The precise mechanism of DOX-induced cardiotoxicity is still unclear but oxidative stress is a pivotal mechanism in DOX-induced cardiotoxicity. DOX causes senescence in cardiac tissues, a key driver of aging and damage-associated loss of tissue homeostasis mediated by oxidative stress. Therefore, attenuation of DOX-induced oxidative stress could be a key strategy in alleviating DOX-induced cardiotoxicity. Accumulative evidence suggests antioxidants such as quercetin (a naturally occurring flavonoid abundant in fruits and vegetables) have beneficial effect in the protection of oxidative stress-induced cell death. Purpose The aim of this study is to investigate the putative cardioprotective effects of antioxidants against DOX and hydrogen peroxide-induced H9c2 cell death. Methods H9C2 cells were seeded (5000 cells/well) onto 96-well plates and pre-treated with either quercetin (50μM), melatonin (1μM) or in combination for 24 hours. Thereafter, some cells were treated with DOX (10-400 μM), DMSO (10-40%), or hydrogen peroxide (0.25-1 mM) for 2 hours. In some assays, cells were pre-treated with either ferrostatin (50uM) or necrostatin (100μM) for 24 hours before treatment with DOX (200μM) or hydrogen peroxide (500μM) for 2 hours. Cell viability was assayed using the MTT and alamarBlue assays. Statistical analyses were conducted using a one-way ANOVA with Tukey’s post hoc test and data plotted as mean ± SD. Results Doxorubicin, hydrogen peroxide and DMSO dose-dependently reduced H9c2 cell viability (n=5 separate experiments,10 wells per treatment group) when compared to untreated control cells (p<0.0001). Doxorubicin (200uM), DMSO (20%) and hydrogen peroxide (500uM) treatment (2 hours) resulted in 55+/-7%, 65 +/- 6% and 19+/- 5.6% cell viability, respectively. However, pre-treatment with quercetin (50μM) completely blocked DOX-cardiotoxicity and attenuated hydrogen-peroxide induced death by increasing cell viability from 19% to 58 +/- 6% (p<0.05). Ferrostatin (50 μM) pretreatment also provided a similar profile of inhibition for DOX and hydrogen-peroxide induced cell death. Necrostatin had no effect on drug-induced cell death. Cells pre-treated with quercetin (50μM), ferrostatin (50μM and necrostatin (50μM) had no significant effect on cell viability (p>0.05). Conclusions Simulated oxidative stress (DOX and hydrogen peroxide) induced dose-dependent cell death in h9c2 cells which was attenuated by quercetin and ferrostatin. It is conceivable that a key mechanism of quercetin is via the blockade of ferroptosis an provides a platform as novel natural therapeutics against DOX-induced cardiotoxicity.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| 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 | 0,001 |
| 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 découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».