title: Protective effect of pretreatment with cilostazol on cytotoxicity of cadmium and arsenite in cultured vascular endothelial cells.
abstract: Cilostazol, an antiplatelet drug, exhibits antiatherogenic effects. The purpose of the present study was to determine the effect of cilostazol on the cytotoxicity of cadmium (Cd) and arsenite (iAs(III)), which involved in the pathogenesis of vascular disorders such as atherosclerosis, in cultured vascular endothelial cells. Cytotoxicity was evaluated by the lactate dehydrogenase leakage assay and morphological observation. Cd (10 µM) -induced cytotoxicity was prevented by pretreatment with cilostazol (30 and 100 µM) and simultaneous treatment with cilostazol (100 µM). On the other hand, iAs(III)-induced cytotoxicity was blocked by pretreatment with cilostazol (30 and 100 µM) but not simultaneous treatment with cilostazol. The mRNA level and the protein level of metallothionein (MT) were significantly increased by cilostazol in the cells. These results suggested, therefore, that pretreatment with cilostazol effectively prevents the cytotoxicity of Cd and iAs(III) in cultured vascular endothelial cells, at least in part through the induction of MT synthesis.
authors.affiliation: Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Hiroki
authors.initials: H
authors.lastname: Banno
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shinkai
authors.forename: Chika
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaji
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D018053:Arsenites / Q000633:toxicity*; D015153:Blotting, Western; D019256:Cadmium Chloride / Q000633:toxicity*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000077407:Cilostazol; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017670:Sodium Compounds / Q000633:toxicity*; D013777:Tetrazoles / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D018053:Arsenites; D012333:RNA, Messenger; D017670:Sodium Compounds; D013777:Tetrazoles; D014665:Vasodilator Agents; C017947:sodium arsenite; D008668:Metallothionein; D007770:L-Lactate Dehydrogenase; D019256:Cadmium Chloride; D000077407:Cilostazol