title: Sesamin protects mouse liver against nickel-induced oxidative DNA damage and apoptosis by the PI3K-Akt pathway.
abstract: Sesamin (Ses), one of the major lignans in sesame seeds and oil, has been reported to have many benefits and medicinal properties. However, its protective effects against nickel (Ni)-induced injury in liver have not been clarified. The aim of the present study was to investigate the effects of sesamin on hepatic oxidative DNA injury and apoptosis in mice exposed to nickel. Kunming mice were exposed to nickel sulfate with or without sesamin coadministration for 20 days. The data showed that sesamin significantly prevented nickel-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, nickel-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by an increase of the lipid peroxidation level and depletion of the intracellular reduced glutathione (GSH) level in liver, were suppressed by treatment with sesamin. Sesamin also restored the activities of antioxidant enzymes (T-SOD, CAT, and GPx) and decreased 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in nickel-treated mice. Furthermore, a TUNEL assay showed that nickel-induced apoptosis in mouse liver was significantly inhibited by sesamin. Exploration of the underlying mechanisms of sesamin action revealed that activities of caspase-3 were markedly inhibited by the treatment of sesamin in the liver of nickel-treated mice. Sesamin increased expression levels of phosphoinositide-3-kinase (PI3K) and phosphorylated protein kinase B (PBK/Akt) in liver, which in turn inactivated pro-apoptotic signaling events, restoring the balance between pro- and anti-apoptotic Bcl-2 proteins in the liver of nickel-treated mice. In conclusion, these results suggested that the inhibition of nickel-induced apoptosis by sesamin is due at least in part to its antioxidant activity and its ability to modulate the PI3K-Akt signaling pathway.
authors: School of Life Science, The Key Laboratory of Biotechnology for Medical Plant of Jiangsu Province, Jiangsu Normal University, No. 101 Shanghai Road, Tangshan New Area, Xuzhou City 221116, Xuzhou City, Jiangsu Province, People's Republic of China. lcm9009@126.com
authors: Chan-Min
authors: CM
authors: Liu
authors: Gui-Hong
authors: GH
authors: Zheng
authors: Qing-Lei
authors: QL
authors: Ming
authors: Cheng
authors: C
authors: Chao
authors: Jian-Mei
authors: JM
authors: Sun
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology*; D005978:Glutathione; D020287:In Situ Nick-End Labeling; D017705:Lignans / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009532:Nickel / Q000009:adverse effects*; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D053148:Caspase 3; D003849:Deoxyguanosine; D004149:Dioxoles; D005978:Glutathione; D017705:Lignans; D009532:Nickel; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C029938:nickel sulfate; C505409:Casp3 protein, mouse; C054125:sesamin