Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl2). The results showed that luteolin ameliorated HgCl2 induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo. Furthermore, luteolin reversed the changes in levels of inflammation- and apoptosis-related proteins involving NF-κB, TNF-α, Sirt1, mTOR, Bax, p53, and Bcl-2, and inhibited p38 MAPK activation. Luteolin enhanced antioxidant defense system based on Keap1, Nrf2, HO-1, NQO1, and KLF9. Moreover, luteolin did not affect miRNA-146a expression. Collectively, our findings, for the first time, elucidate a precise mechanism for attenuation of HgCl2-induced liver dysfunction by dietary luteolin via regulating Sirt1/Nrf2/TNF-α signaling pathway, and provide a foundation for further study of luteolin as a novel therapeutic agent against inorganic mercury poisoning.
Animals may suffer from a variety of environmental stressors every day, among which is cold stress, which commonly exists in cold regions. The aim of this study was to investigate changes in antioxidative function and inducible nitric oxide synthase-nitric oxide (iNOS-NO) system activity in the duodenum of chicks as a reaction to cold stress. A total of 84 male chicks (15 d old) were randomly allocated to 12 groups (7 chickens/group). There were 1 control group and 5 treatment groups for acute cold stress and 3 control groups and 3 treatment groups for chronic cold stress. Antioxidative function was examined by superoxide dismutase (SOD), and oxidative damage was examined by malondialdehyde (MDA) detection. The iNOS-NO system activity was identified by NO content and NOS activity assay, and the transcription of iNOS mRNA was tested by fluorescence quantitative PCR. The results showed that under acute cold stress MDA level increased, the activity of NO in the duodenum fluctuated, and the activity of SOD and iNOS in the duodenum first increased and then decreased, whereas the expression of iNOS mRNA decreased. Under chronic cold stress the activity of SOD, NO, and NOS first decreased and then increased, whereas the MDA level and the expression of iNOS mRNA increased. The results indicated that both acute and chronic cold stress could cause duodenum oxidative stress and change in iNOS, which was related to the intestinal damage process.
Lead (Pb) is a global environmental health hazard that leads to nephrotoxicity. However, the effective treatment of Pb-induced nephrotoxicity remains elusive. Grape seed procyanidin extract (GSPE) has beneficial properties for multiple biological functions. Therefore, the present study investigated whether GSPE reduced Pb-induced nephrotoxicity as well as the protective mechanism of GSPE in a well-established 35-day Pb induced nephrotoxicity rat model. The results showed that GSPE normalized Pb-induced oxidative stress, histological damage, inflammatory, apoptosis, and changes of miR153 and glycogen synthase kinase 3β (GSK-3β) levels in rat kidney. Moreover, GSPE enhanced the induction of phase II detoxifying enzymes (heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1) by increasing nuclear factor-erythroid-2-related factor 2 (Nrf2) expression. This study identifies for the first time that Pb-induced oxidative stress in rat kidney is attenuated by GSPE treatment via activating Nrf2 signaling pathway and suppressing miR153 and GSK-3β. Nrf2 signaling provides a new therapeutic target for renal injury induced by Pb, and GSPE could be a potential natural agent to protect against Pb-induced nephrotoxicity.
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