Arecoline is cytotoxic for human endothelial cells.

[oral submucous fibrosis]

Oral submucous fibrosis is a pre-malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity . Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts . Endothelial cell cycle arrest is reported on exposure to arecoline , as is cytotoxicity for endothelial-lung carcinoma hybrid cells . We here describe cytotoxicity for primary human endothelial cultures from seven separate donors .Human umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by : phase-contrast microscopy , haemocytometer counts , transmission electron microscopy , lactate dehydrogenase release and the methyl-thiazol-tetrazolium assay .Vacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333 Â Î¼g /ml or more . Ultrastructural features of cellular stress were seen after 24 -h treatment with 111 Â Î¼g /ml arecoline and included reduced ribosomal studding of endoplasmic reticulum , increased autophagolysosomal structures , increased vacuolation and reduced mitochondrial cristae with slight swelling . Similar changes were seen at 4 Â h with arecoline at 333 Â Î¼g /ml or above , but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling , while by 24 Â h , these cells were frankly necrotic . Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl-thiazol-tetrazolium assays .Arecoline is cytotoxic via necrosis for endothelium , while biochemical assays indicate no appreciable cellular leakage before death and detachment , as well as no clear effect on mitochondrial function in viable cells . Arecoline toxicity may thus contribute to reduced vascularity in oral submucous fibrosis .

Diseases
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Diseases presenting "appreciable cellular leakage" symptom

oral submucous fibrosis

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