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Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
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Arecoline is cytotoxic for human endothelial cells
Mafaz Ullah1, Stephen Cox, Elizabeth Kelly
1Cellular and Molecular Pathology Research Unit, Department of Oral Pathology and Oral Medicine, Westmead Centre for Oral Health, Westmead Hospital, The University of Sydney, Westmead, NSW, Australia.
Summary
Arecoline, a key component of areca nut, causes endothelial cell death through necrosis. This cytotoxicity may explain the reduced vascularity observed in oral submucous fibrosis, a condition linked to areca nut use.
Area of Science:
- Cell Biology
- Toxicology
- Oral Pathology
Background:
- Oral submucous fibrosis is a pre-malignant condition linked to areca nut consumption.
- Areca nut use leads to reduced mucosal vascularity.
- Arecoline, the primary alkaloid in areca nut, is known to be cytotoxic.
Purpose of the Study:
- To investigate the cytotoxic effects of arecoline on primary human endothelial cells.
- To determine the mechanism of arecoline-induced endothelial cell death.
- To explore the role of arecoline toxicity in the vascular changes associated with oral submucous fibrosis.
Main Methods:
- Primary human umbilical vein endothelial cells were exposed to varying concentrations of arecoline.
- Cell viability was assessed using phase-contrast microscopy, haemocytometer counts, and methyl-thiazol-tetrazolium assays.
- Cellular damage was evaluated through transmission electron microscopy and lactate dehydrogenase release assays.
Main Results:
- Arecoline induced vacuolation and detachment of endothelial cells at concentrations of 333 μg/ml and above.
- Ultrastructural analysis revealed cellular stress, including mitochondrial damage and increased autophagolysosomal structures, after arecoline exposure.
- Biochemical assays confirmed cell death via necrosis, with no significant leakage or mitochondrial dysfunction in viable cells prior to detachment.
Conclusions:
- Arecoline is cytotoxic to endothelial cells, causing death by necrosis.
- The biochemical assays did not show significant cellular leakage or mitochondrial dysfunction in viable cells before detachment.
- Arecoline-induced endothelial cell toxicity is a potential contributing factor to the reduced vascularity in oral submucous fibrosis.
