title: Allylmethylsulfide Down-Regulates X-Ray Irradiation-Induced Nuclear Factor-kappaB Signaling in C57/BL6 Mouse Kidney.
abstract: Allylmethylsulfide (AMS), a volatile organosulfur derivative from garlic, has been shown to have radioprotective effects in radiation-challenged cell and animal models, but the mechanism of radioprotection is not well understood. To determine the mechanism of radioprotection in an in vivo model, we first verified the antioxidant capacity of AMS using 2,2'-azobis(2-amidinopropane) dihydrochloride-induced human embryonic kidney 293T cells by measuring reactive oxygen species generation, reduced glutathione, protein tyrosine kinase/protein tyrosine phosphatase balance, and nuclear factor-kappaB (NF-kappaB) protein levels. We then investigated the protective effects of AMS (55 and 275 micromol/kg, intraperitoneal treatment) on 15 Gy X-ray-irradiated mouse kidney. The results showed that AMS decreased the free radical-induced lipid peroxidation in mice exposed to X-rays. Moreover, the antioxidative AMS suppressed the activation of NF-kappaB and its dependent genes such as vascular cell adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2 through inhibition of IkappaBalpha phosphorylation and activation of IkappaB kinase alpha/beta and mitogen-activated protein kinases (MAPKs). Based on these results, AMS may be a useful radioprotective agent by down-regulating the MAPKs and NF-kappaB signaling pathway that can be induced via X-ray irradiation.
authors.affiliation: Department of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Sang Woon
authors.initials: SW
authors.lastname: Chung
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Hyoung-Sam
authors.initials: HS
authors.lastname: Heo
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Lim
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Stephen
authors.initials: S
authors.lastname: Anton
authors.forename: Takako
authors.initials: T
authors.lastname: Yokozawa
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation; D005737:Garlic / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000528:radiation effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011832:Radiation Injuries / Q000188:drug therapy; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013440:Sulfides / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014965:X-Rays
chemical_list: D000498:Allyl Compounds; D000975:Antioxidants; D016328:NF-kappa B; D010936:Plant Extracts; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D013440:Sulfides; D019010:Vascular Cell Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; C077207:allyl methyl sulfide