Defibrotide protects endothelial cells, but not L929 tumour cells, from tumour necrosis factor-alpha-mediated cytotoxicity.
The effect of defibrotide on the cytotoxicity of tumour necrosis factor-alpha was investigated in cultured bovine pulmonary artery endothelial cells and L929 mouse tumour cells. In endothelial cells, a 72-h incubation with tumour necrosis factor-alpha (1 and 10 ng mL-1) reduced the number of viable cells to 63 and 51% of control, respectively. Simultaneous incubation with defibrotide (0.03-0.3 mg mL-1) protected endothelial cells from tumour necrosis factor-alpha-mediated cytotoxicity, and increased viability in a concentration-dependent fashion to 98% of control at 1 ng mL-1 tumour necrosis factor-alpha and to 80% of control at 10 ng mL-1 tumour necrosis factor-alpha. However, under the same conditions a similar cytotoxic response to tumour necrosis factor-alpha in L929 tumour cells remained unaltered in the presence of defibrotide. These findings demonstrate protection from tumour necrosis factor-alpha-mediated toxicity by defibrotide in endothelial cells but not in a tumour cell line. It is concluded that defibrotide might serve as a therapeutic agent to limit the vascular toxicity of tumour necrosis factor-alpha without affecting its antineoplastic activity.
Schröder
H
H
Department of Pharmacology, Heinrich Heine University, Düsseldorf, Germany.
D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011089:Polydeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; C036901:defibrotide