title: Protective effect of quercetin on lead-induced oxidative stress and endoplasmic reticulum stress in rat liver via the IRE1/JNK and PI3K/Akt pathway.
abstract: Lead (Pb), a well-known environmental toxin, is one of the major hazards for human health. Quercetin (QE), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against Pb-induced endoplasmic reticulum (ER) stress in liver have not been clarified. The aim of the present study was to investigate the effects of quercetin on hepatic ER stress in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water with or without quercetin co-administration for 75 days. Our data showed that quercetin significantly prevented Pb-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage and histopathological analysis. Quercetin markedly decreased Pb contents in blood and liver. Western blot analysis showed that Pb-induced ER stress in rat liver was significantly inhibited by quercetin. In exploring the underlying mechanisms of quercetin action, we found quercetin markedly suppressed Pb-induced oxidative stress. Quercetin decreased reactive oxygen species (ROS) production and increased the total antioxidant capacity in rat livers. Additionally, quercetin dramatically increased Phosphoinositide-3-kinase (PI3K) and phosphorylated protein kinase B (PKB/Akt) levels in liver rats. In the examined unfolded protein response (UPR) pathways, quercetin markedly inhibited the Pb-induced increase of the phosphorylated inositol-requiring enzyme 1 (IRE1) and c-jun N-terminal kinase (JNK) in rat liver. Taken together, these results suggested that the inhibition of Pb-induced ER stress by quercetin is due at least in part to its anti-oxidant stress activity and its ability to modulate the PI3K/Akt and IRE1/JNK signaling pathway.
authors.affiliation: School of Life Science, The Key Laboratory of Biotechnology for Medical Plant of Jiangsu Province, Jiangsu Normal University , Tangshan New Area, Xuzhou City, Jiangsu Province , P R China. lcm9009@126.com
authors.forename: C-M
authors.initials: CM
authors.lastname: Liu
authors.forename: G H
authors.initials: GH
authors.lastname: Zheng
authors.forename: Q L
authors.initials: QL
authors.lastname: Ming
authors.forename: J M
authors.initials: JM
authors.lastname: Sun
authors.forename: C
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D060766:Drinking Water / Q000737:chemistry; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D000975:Antioxidants; D060766:Drinking Water; D048031:JNK Mitogen-Activated Protein Kinases; D008565:Membrane Proteins; D009942:Organometallic Compounds; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011794:Quercetin; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; C486557:Ern2 protein, rat; C008261:lead acetate