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.

Nickel Chloride (NiCl2) Induces Histopathological Lesions via Oxidative Damage in the Broiler’s Bursa of Fabricius

“…Some studies have reported that NiCl 2 can decrease the activities of enzymic and non-enzymic antioxidants in rats, Tigriopus japonicus Mori, and goldfish [39][40][41]. Also, our data are consistent with the report that NiSO 4 can decrease the SOD and CAT activities in the liver of mouse [42]. GSH contents are decreased in the bursa of NiCl 2 -treated broilers, which is in agreement with the previous study [43].…”

NiCl2-Down-Regulated Antioxidant Enzyme mRNA Expression Causes Oxidative Damage in the Broiler’s Kidney

“…In addition, we found that NiCl 2 increased 8-OHdG contents, which is widely used as sensitive biomarkers of DNA oxidation [29]. This tendency is similar to the results of the study by Liu [12], who has found that NiSO 4 can induce an increase in 8-OHdG contents in the liver of mouse.…”

“…Nickel sulfate (NiSO 4 ) can enhance lipid peroxidation (LPO) and reduce glutathione (GSH) contents, the activities of catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver of mouse [12]. Also, nickel chloride (NiCl 2 ) can decrease GSH contents in the Tigriopus japonicus [13] and can cause oxidative damage in the spleen, small intestines, and cecal tonsil of broilers [14][15][16].…”

Carbon tetrachloride-induced lethality in mouse is prevented by multiple pretreatment with zinc sulfate

“…CCl 4 is metabolized to trichloromethyl radicals and trichloromethyl peroxy radical by cytochrome P450 in liver microsomes. These free radicals are thought to react with membrane lipids to induce peroxidation and subsequent dysfunction of membranes, thereby causing injuries to liver, kidney, heart, testis, and brain (Ciccoli et al, 1978;Ahmad et al, 1987;Singh et al, 2008;Domitrović et al, 2011;Liu et al, 2013).…”