Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in 
vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector 
against doxorubicin-induced cardiotoxicity in vivo. It is not known yet whether 
monoHER can also protect against doxorubicin-induced inflammatory effects. The 
aim of the present study was (1) to illustrate the inflammatory effects of 
doxorubicin in vitro and (2) to evaluate a possibly protective effect of 
monoHER. In order to demonstrate the inflammatory effects of doxorubicin and the 
possible protection of monoHER, proliferating human umbilical cord vascular 
endothelial cells (HUVECs) were incubated with different concentrations of 
doxorubicin ranging from 12.5 to 600 nM with(out) 200 micro M monoHER. Resting 
(confluent) HUVECs were incubated with (0.5-25 micro M) doxorubicin with(out) 
monoHER (0.2-1.2 mM) and the viability of endothelial cells and their propensity 
to adhere to neutrophils were measured 24 h after treatment. The localisation of 
adhered neutrophils was determined with immunofluorescence microscopy. To 
further characterise the mechanism of doxorubicin-induced neutrophil adhesion, 
the expression of the HUVECs surface adhesion molecules was determined after 
doxorubicin treatment. Doxorubicin decreased the viability and proliferation 
capacity of HUVECs in a concentration-dependent manner. The proliferating HUVECs 
were much more sensitive to doxorubicin (IC(50)=60.0+/-20.8 nM) than resting 
cells (LC(50)=4.0+/-0.3 micro M). Doxorubicin also increased the adhesion of 
neutrophils reaching a plateau value at a doxorubicin concentration of > or =0.4 
micro M (P=0.0113). The induced neutrophil adhesion was accompanied by 
overexpression of VCAM and E-selectin but not ICAM. Although monoHER did not 
reverse the effect of doxorubicin on the proliferation of endothelial cells, it 
significantly protected resting HUVECs against the cytotoxic effect of 
doxorubicin (< or =25 micro M, P<0.0015). In addition, monoHER completely 
protected against the stimulatory effect of doxorubicin on neutrophil adhesion, 
and inhibited the doxorubin-induced expression of VCAM and E-selectin on the 
surface of treated HUVECs. This study illustrates that monoHER, which protects 
against doxorubicin's cardiotoxic effect, can also protect against 
doxorubicin-induced inflammatory effects. These data prompt further 
investigation about the possible link between doxorubicin-induced inflammatory 
effects and its cardiotoxicity in vivo.