Ultrastructural Damage in Vascular Endothelium in Rats Treated with Paclitaxel and Doxorubicin

Abstract

Endothelium is the first physiological barrier between blood and tissues and can be injured by physical or chemical stress, particularly by the drugs used in the cancer therapy. Paclitaxel and doxorubicin are frequently used anticancer drugs and their cardiac side effects are well observed in clinical setting. Their side effects on the endothelium are still not clear enough. There are few investigations assessing the damages elicited by the combination use of chemotherapy agents in animal experimental models. The purpose of this study was to examine and compare the side effects of doxorubicin and paclitaxel on endothelium in vivo. The drugs were administered weekly to rats via intraperitoneal injections singly or in combinations. Lastly, aorta endothelium was examined. The most familiar parts of the aorta endothelium are the nucleus, free ribosomes, Weibel-Palada granules, plasmalemmal vesicles, and clear basement membrane. Examination of the endothelium and the related structures revealed some clear degenerative findings. Notably, administration of a paclitaxel and doxorubicin combinations caused the most dramatic change in ultrastructure, which may disrupt many functions of the endothelium.

Ultrastructural damage in lung tissues in rats treated with doxorubicin and paclitaxel

“…All groups, including the control group, were given premedication which included H 1 receptor blocker (chlorphenoxamine HCl: 0.16 mg/kg), H 2 receptor blocker (ranitidine: 2.5 mg/kg), and a steroid (dexamethasone: 0.015 mg/kg). 7 After 14 weeks of injections and a 3-week observation period, the rats were killed. They were anaesthetised with thiopental sodium (30 mg/kg), and left median lung tissue samples were removed for examination.…”

Urokinase Receptor Mediates Doxorubicin-Induced Vascular Smooth Muscle Cell Senescence via Proteasomal Degradation of TRF2

“…However, little is known about its vascular toxicity. A couple of reports documented damage to the vascular endothelium in response to doxorubicin [4], which is most likely related to doxorubicin-induced apoptosis of endothelial cells [5,6]. Even less is known about the effects of doxorubicin treatment on vascular smooth muscle cells (VSMC), though deregulation of these cells is one of the key events contributing to negative vascular remodeling and dysfunction [7].…”

Effects of adriamycin and candesartan on the collagen and elastin of the aorta in rats

“…It has been reported that adriamycin induces aortic toxicity [14]. However, the mechanisms of adriamycin-induced aortopathy are not known in detail.…”

“…However, the mechanisms of adriamycin-induced aortopathy are not known in detail. The suggested mechanisms of adriamycin-induced vasculopathy were endothelial dysfunction [15–18], suppression of endothelin-1 in endothelial cells [19], degeneration of endothelial structures [14], apoptosis of the endothelial cells [20], enhancement of procoagulant activity [21], smooth muscle dysfunction, and dysregulation of its calcium contents [10, 22]. In addition, adriamycin could induce not only cardiovascular toxicity but also nephrotoxicity by alteration of glomerular endothelial cells [16, 23].…”