Red wine polyphenols prevented doxorubicin-induced blunted EDH-type relaxations and increased vascular oxidative stress, improving the expression levels of target proteins in rat mesenteric arteries.
Do red wine polyphenols prevent doxorubicin-induced impairment of endothelium-dependent relaxations in male Wistar rats?
Red wine polyphenols prevent doxorubicin-induced vascular injury in rats by preserving EDH-mediated relaxations and reducing oxidative stress.
This study determined whether doxorubicin, an anticancer agent, impairs endothelium-dependent relaxations mediated by nitric oxide (NO) and endothelium-derived hyperpolarization (EDH) in the mesenteric artery and, if so, the mechanism underlying the protective effect of red wine polyphenols (RWPs), a rich natural source of antioxidants. Male Wistar rats were assigned into 4 groups: control, RWPs, doxorubicin, and doxorubicin + RWPs. Vascular reactivity was assessed in organ chambers; the vascular formation of reactive oxygen species (ROS) using dihydroethidine and the expression levels of small and intermediate conductance calcium-activated potassium channels (SKCa, IKCa) and connexin 40 (Cx40), which are involved in EDH-type relaxations, endothelial NO synthase (eNOS), angiotensin II, and AT1 receptors by immunofluorescence. The doxorubicin treatment impaired EDH-mediated relaxations, whereas those mediated by NO were minimally affected. This effect was associated with reduced expression levels of SKCa, IKCa, and Cx40, increased expression levels of eNOS, angiotensin II, and AT1 receptors, and formation of ROS in mesenteric arteries. RWPs prevented both the doxorubicin-induced blunted EDH-type relaxations and the increased vascular oxidative stress, and they improved the expression levels of target proteins. These findings suggest that polyphenol-rich natural products might be of interest in the management of doxorubicin-induced vascular injury possibly by improving the vascular angiotensin system.
Idris-Khodja et al. (Tue,) conducted a other in Doxorubicin-induced vascular injury. Red wine polyphenols (RWPs) vs. Doxorubicin alone was evaluated on EDH-mediated relaxations and vascular oxidative stress. Red wine polyphenols prevented doxorubicin-induced blunted EDH-type relaxations and increased vascular oxidative stress, improving the expression levels of target proteins in rat mesenteric arteries.
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