title: Differential effects of diallyl disulfide on neuronal cells depend on its concentration.
abstract: Diallyl disulfide (DADS) is one of the organosulfur compounds of garlic. The effects of DADS on neuronal cells have not clearly been established. We investigated its effects on the viability of neuronal cells (N18D3 cells), the levels of free radical and membrane lipid peroxidation, and the cell signals, such as phosphatidylinositol 3-kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3). When N18D3 cells were treated with several concentrations of DADS, the viability was not affected up to 25 microM, however, decreased at higher than 25 microM. The levels of free radicals and membrane lipid peroxidation were increased in a dose-dependent manner, especially at higher than 25 microM. The treatment of N18D3 cells with 25 microM DADS slightly increased the expressions of p85a PI3K, phosphorylated Akt and phosphorylated GSK-3, but the treatment with 100 microM significantly reduced them. To evaluate whether low concentration of DADS, up to 25 microM, had protective effect on oxidative stress-injured N18D3 cells, the viability of N18D3 cells (pretreated with DADS for 2h versus not pretreated) was evaluated 24h after their exposure to 100 microM H(2)O(2) for 30 min. Compared to the cells treated with only 100 microM H(2)O(2), the pretreatment with 25 microM DADS increased the viability, and the expressions of p85a PI3K, phosphorylated Akt and phosphorylated GSK-3. These results indicate that low concentration of DADS has protective effects on N18D3 cells, whereas high concentration is rather cytotoxic. Therefore, some specific optimum concentration of DADS may be a new potential therapeutic strategy for oxidative stress-injury in vitro model of neurodegenerative diseases.
authors.affiliation: Department of Toxicological Research, National Institute of Toxicological Research, KFDA, Seoul, South Korea.
authors.forename: Jun-Gyou
authors.initials: JG
authors.lastname: Kim
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Koh
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Kyu-Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Youngchul
authors.initials: Y
authors.lastname: Kim
authors.forename: Sunyoun
authors.initials: S
authors.lastname: Kim
authors.forename: Myung-Koo
authors.initials: MK
authors.lastname: Lee
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000498:Allyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D007211:Indoles; D015227:Lipid Peroxidation / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D013778:Tetrazolium Salts; D013844:Thiazoles; D014343:Trypan Blue
chemical_list: D000498:Allyl Compounds; D004220:Disulfides; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D005609:Free Radicals; D007211:Indoles; D008563:Membrane Lipids; D011518:Proto-Oncogene Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C007293:DAPI; C028009:diallyl disulfide; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C022616:thiazolyl blue; D014343:Trypan Blue