Purchase this article with an account.
Ikram El-zaoui, Fatemeh Valamanesh, Francine F. Behar-Cohen, Alicia Torriglia; Corticosteroids-induced Toxicity And Cell Death Mechanisms In Vascular Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4323.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Glucocorticosteroids have been widely used in the treatment of many diseases. In the eye they are used in the treatment of macular oedema and retinal neo-vascularization, currently associated with diabetic retinopathies. Previous work have shown a toxicity of glucocorticosteroids on several retinal cells, like retinal endothelial cells, Muller cells and Retinal pigmented epithelial cells. In all these cells we have shown that cell death is triggered through non conventional molecular mechanisms, e.g. caspase independent mechanisms. We investigate here the toxicity of these compounds on endothelial cells of the microcirculation.
We performed our study on cells of the human microcirculation (HMEC) and bovine retinal endothelial cells (BREC). Four glucocorticosteroids were used : hydrocortisone, dexamethasone, dexamethasone phosphate and triamcinolone acetonide). DL50 for these compounds were evaluated though MTT test. Mechanisms of cells death have been explored using the evaluation of lactate dehydrogenase release, DNA electrophoresis, immunohistochemistry and western blot.
We found a decrease of cell viability that increases with the degree of hydrophobicity of the glucocorticosteroids. The most hydrophobics been the most toxic. DL50 on HMEC was 0.1 mg/ml for hydrocortisone, dexamethasone and triamcinolone acetonide and it was 0.8mg/ml for dexamethasone phosphate. The cell type is also important. We found that the endothelial cells of the general microcirculation are more sensitive that the retinal endothelial cells. The evaluation of the cell death pathways activated showed that activation of a caspase independent pathway, the LEI/L-DNase II is involved in this cell death.
At the therapeutically used doses glucocorticosteroids are toxic for endothelial cells. This should be kept in mind in the clinical use of these compounds.
This PDF is available to Subscribers Only