Xinshuitong Capsule extract attenuates doxorubicin-induced myocardial edema via regulation of cardiac aquaporins in the chronic heart failure rats - 13/11/21
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Abstract |
Doxorubicin (Dox), an effective antineoplastic drug, was limited use for cardiotoxicity. Xinshuitong Capsule (XST), a patented herbal formula, showed desirable beneficial effects in the treatment of chronic heart failure (CHF) patients. However, the drug on Dox-induced cardiotoxicity remains unclear. Ninety male Sprague-Dawley rats were randomized into two groups: 15 rats were selected as the normal group and 75 rats were injected intraperitoneally with Dox to establish CHF rat models, the success ones were randomly divided into five groups: low XST (LXST), medium XST (MXST) or high XST (HXST) (4.9, 9.8, or 19.6 g/kg d) administrated intragastrically twice a day for 4 weeks, with the captopril-treated group and the model group as comparison. The model group showed the cardiac functions generally impaired, and CHF mortality rate higher (47%) than those in the XST-treated groups (averaged 24%, P < 0.05). Compared with XST-treated groups, myocardial remodeling, inflammation and desarcomerization, and higher water content more severe in the cardiac tissue in the model group (P < 0.05), which was associated with higher expressions of mRNA or protein levels of AQP1, 4 and 7. Dox-impaired cardiac functions, cardiac remodeling and myocardial edema could be dose-dependently reverted by XST treatment. XST could inhibit AQP1, 4 and 7 at mRNA levels or at protein levels, which was associated with the attenuation of myocardial edema and cardiac remodeling, decreasing the ventricular stiffness and improving the cardiac functions and rats’ survival. AQPs is involved in cardiac edema composed one of the mechanisms of Dox-induced cardiotoxicity, XSTvia inhibition of AQPs relieved the Dox-induced side effects.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Doxorubicin, via up-regulation of AQPs, caused myocardial edema, myocardial remodeling,cardiac desarcomerization and interstitial fibrosis, which deteriorated the condition of CHF. XST, via inhibition of AQPs, relieved myocardial interstitial edema and attenuated myocardial structure remodeling. XST may become an alternative medicine for Doxorubicin -related CHF.
Highlights |
• | Dox induced myocardial edema as a new adverse side effect. |
• | Dox induced myocardial edema via up-regulation of AQPs. |
• | XST, via inhibition of AQPs, relieved Dox-induced myocardial edema and attenuated myocardial remodeling. |
• | XST may become an alternative medicine for Dox -related cardiotoxicity. |
Abbreviations : AQPs, AQP1, AQP4, AQP7, CHF, Dox, NYHA, XST
Keywords : Xinshuitong Capsule, Aquaporins, Doxorubicin, Myocardial edema, Chronic heart failure
Plan
Vol 144
Article 112261- décembre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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