Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities
Journal
Food and Chemical Toxicology
Journal Volume
37
Journal Issue
7
Pages
751-756
Date Issued
1999
Author(s)
Abstract
Betel quid (BQ) chewing is associated with an increased risk of oral submucous fibrosis (OSF) and oral cancer in India and many south-east Asian countries. Recently, we have shown that arecoline is cytotoxic to cultured human oral mucosal fibroblasts. This study investigated protective effects of various agents against the cytotoxicity of arecoline and its mechanisms. Arecoline, at concentrations of 0.2 and 0.4mM, decreased the cell numbers by 38% and 63%, respectively. At a concentration of 2mM, N-acetyl-L-cysteine [a glutathione (GSH) synthesis precursor] could prevent arecoline-induced cytotoxicity. The decrease in cell numbers was reduced to 17% relative to control. Extracellular addition of esterase at a concentration of 0.1 U/ml could almost completely protect the oral mucosal fibroblast (OMF) from arecoline-induced cytotoxicity. Arecoline is a muscarinic receptor agonist. However, atropine, a muscarinic receptor antagonist was unable to protect the cells from arecoline cytotoxicity at a concentration of 10 μM. Pretreatment of OMF with 50 μM buthionine sulfoximine (a cellular GSH synthesis inhibitor) or 0.5mM diethylmaleate (a cellular GSH depleting agent) potentiated the cytotoxic effects of arecoline. These results indicate that cytotoxicity of arecoline on OMF is associated with cellular GSH levels and esterase activities. Factors that induce the GSH synthesis or esterase activity of oral mucosal cells can be used for future chemoprevention of BQ chewing-related lesions. Copyright (C) 1999 Elsevier Science Ltd.
SDGs
Other Subjects
arecoline; esterase; glutathione; thiol; article; betel nut; cell death; cell protection; controlled study; cytotoxicity; fibroblast; human; human cell; metabolism; mouth mucosa; Acetylcysteine; Antimetabolites; Areca; Arecoline; Atropine; Buthionine Sulfoximine; Cell Survival; Cells, Cultured; Esterases; Expectorants; Fibroblasts; Ganglionic Stimulants; Humans; Maleates; Mouth Mucosa; Muscarinic Antagonists; Plants, Medicinal; Sulfhydryl Compounds; Thiolester Hydrolases; Piper betel
Type
journal article