Effects of probucol on endothelial damage by 5-fluorouracil.
Cardiotoxicity is a serious side effect of cancer treatment with the commonly used drug 5-fluorouracil (5-FU). The pathophysiology of this is unclear. Experimental studies show a thrombogenic effect of 5-FU, secondary to a direct toxic effect on the endothelium, possibly mediated by radical generation. Probucol is a lipid-lowering drug with strong antioxidant properties. The aim of this study was to evaluate the possibility of using probucol treatment to protect against the toxicity of 5-FU on vascular endothelium of the central artery in the ears of rabbits. Five groups of rabbits were treated with 1) 5-FU, 2) saline, 3) probucol high-dose and saline, 4) probucol high-dose and 5-FU, 5) probucol low-dose and 5-FU. Damage to the arterial endothelium was evaluated by scanning electron microscopy. Damage to the endothelium in 5-FU + probucol-treated animals was minimal and comparable to that of the control group. Intima disruption or thrombus formation was seen with 5-FU only. The results of the study indicate that treatment with probucol prevents 5-FU-induced endothelial injury.
Kinhult
Sara
S
Department of Oncology, University Hospital, Lund, Sweden. sara.kinhult@onk.lu.se
Albertsson
Maria
M
Eskilsson
Jan
J
Cwikiel
Magdalena
M
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D001158:Arteries / Q000187:drug effects / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D005472:Fluorouracil / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008297:Male; D008855:Microscopy, Electron, Scanning; D011341:Probucol / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D013927:Thrombosis / Q000139:chemically induced / Q000517:prevention & control*
D000924:Anticholesteremic Agents; D000964:Antimetabolites, Antineoplastic; D011341:Probucol; D005472:Fluorouracil