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Henning Schröder, Defibrotide Protects Endothelial Cells, but not L929 Tumour Cells, from Tumour Necrosis Factor-α-mediated Cytotoxicity, Journal of Pharmacy and Pharmacology, Volume 47, Issue 3, March 1995, Pages 250–252, https://doi.org/10.1111/j.2042-7158.1995.tb05789.x
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Abstract
The effect of defibrotide on the cytotoxicity of tumour necrosis factor-α 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-α (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-α-mediated cytotoxicity, and increased viability in a concentration-dependent fashion to 98% of control at 1 ng mL−1 tumour necrosis factor-α and to 80% of control at 10 ng mL−1 tumour necrosis factor-α. However, under the same conditions a similar cytotoxic response to tumour necrosis factor-α in L929 tumour cells remained unaltered in the presence of defibrotide.
These findings demonstrate protection from tumour necrosis factor-α-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-α without affecting its antineoplastic activity.