JIIANG-HUEI JENGHahn, LiangjiunnLiangjiunnHahnLu, F. J.F. J.LuWang, YingjangYingjangWangYEN-PING KUO2021-07-052021-07-0519940022-0345https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028433013&doi=10.1177%2f00220345940730050601&partnerID=40&md5=43f0462ef2d7599d8cc0eb2a4c7d2da9https://scholars.lib.ntu.edu.tw/handle/123456789/569243Pathobiological effects of eugenol (4-allyl-2-methoxyphenol), a major constituent of betel quid (BQ), were studied on oral mucosal fibroblasts. At a concentration higher than 3 mmol/L, eugenol was cytotoxic to oral mucosal fibroblasts in a concentration-and time-dependent manner. Cell death was associated with intracellular depletion of glutathione (GSH). Most of the GSH was depleted prior to the onset of cell death. At concentrations of 3 mmol/L and 4 mmol/L, eugenol depleted about 45% and 77% of GSH after one-hour incubation. In addition, eugenol decreased cellular ATP level in a concentration- and time-dependent manner. Eugenol also inhibited lipid peroxidation. Inhibition of lipid peroxidation was partially explained by its dose-dependent inhibition of xanthine oxidase activity. The IC50 of eugenol on xanthine oxidase activity was about 0.3 mmol/L. No DNA strand break activity for eugenol was found at concentrations between 0.5 and 3 mmol/L. Taken together, frequent exposure of oral mucosa to a high concentration of eugenol during the chewing of BQ might be involved in the pathogenesis of oral submucous fibrosis and oral cancer via its cytotoxicity. In contrast, eugenol at a concentration less than 1 mmol/L might protect cells from the genetic attack of reactive oxygen species via inhibition of xanthine oxidase activity and lipid peroxidation. ? 1994, SAGE Publications. All rights reserved.[SDGs]SDG3adenosine triphosphate; eugenol; glutathione; mutagenic agent; xanthine oxidase; article; betel nut; chemistry; DNA damage; dose response; drug effect; fibroblast; human; lipid peroxidation; medicinal plant; mouth mucosa; mutagen testing; Adenosine Triphosphate; Areca; DNA Damage; Dose-Response Relationship, Drug; Eugenol; Fibroblasts; Glutathione; Human; Lipid Peroxidation; Mouth Mucosa; Mutagenicity Tests; Mutagens; Plants, Medicinal; Support, Non-U.S. Gov't; Xanthine Oxidasejournal article10.1177/0022034594073005060180062312-s2.0-0028433013