Key result
Kaempferol protected vascular endothelium against doxorubicin-induced damage by regulating 14-3-3γ and the ADMA/DDAHⅡ/eNOS/NO pathway, inhibiting oxidative stress, and improving mitochondrial function.
Why the study?
Doxorubicin causes ROS generation inducing endotheliotoxicity and cardiotoxicity, and it was hypothesized that kaempferol could protect vascular endothelium by regulating 14-3-3γ or related pathways.
Kaempferol protects vascular endothelial cells from doxorubicin-induced toxicity by regulating the 14-3-3γ pathway and improving mitochondrial function in a preclinical model.
Answers are grounded in this paper and cite their sources.
Kaempferol may protect HUVECs from doxorubicin toxicity in vitro; leaves open clinical cardioprotection pending in vivo confirmation.
Kaempferol (Kae), a flavonoid, has been found in fruits and other vegetables, possesses many biological activities. 14-3-3 protein exerts protection on various types of injured tissues and cells. Doxorubicin (Dox) causes excessive reactive oxygen species (ROS) generation, which induces endotheliotoxicity and cardiotoxicity. We hypothesized that Kae could protect vascular endothelium by regulating 14-3-3γ or related pathways against Dox toxicity. HUVECs were established Dox-toxic injury models. Kae’s effects were assessed with many physiological, enzymatic, cellular, and molecular biological indexes. Our results showed that Dox-induced damage in HUVECs were reduced through Kae to promote the expression of total protein 14-3-3γ and mitochondrial Bcl-2, phosphorylate Bad, increase cell viability, NO content, DDAHⅡactivity, p-eNOS/eNOS ratio, and MMP levels, maintained NAD+/NADH and GSH/GSSG balance, and decrease LDH and caspase-3 activities, ADMA content, ROS generation, mPTP openness, and apoptosis. Kae’s effects were abolished with pAD/14-3-3γ-shRNA downregulating 14-3-3γ expression, or ABT-737 inhibiting Bcl-2 activity. This study demonstrated that Kae protected the vascular endothelium against Dox-induced damage by regulating 14-3-3γ and ADMA/DDAHⅡ/eNOS/NO pathway, inhibiting oxidative stress, and improving mitochondrial function.
No takes yet. Share an insight, caveat, or question.
Wu et al. (2020) studied Doxorubicin-induced endotheliotoxicity. Kaempferol vs. Doxorubicin alone was evaluated on Dox-induced damage in HUVECs. Kaempferol protected vascular endothelium against doxorubicin-induced damage by regulating 14-3-3γ and the ADMA/DDAHⅡ/eNOS/NO pathway, inhibiting oxidative stress, and improving mitochondrial function.
Synapse has enriched 10 related papers. Consider them for comparative context: