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1.
Free Radic Res ; 47(3): 192-201, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23249147

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.


Subject(s)
Antioxidants/pharmacology , Chemical and Drug Induced Liver Injury/enzymology , Endoplasmic Reticulum Stress/drug effects , Organometallic Compounds/toxicity , Oxidative Stress/drug effects , Quercetin/pharmacology , Animals , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Drinking Water/chemistry , Enzyme Activation/drug effects , JNK Mitogen-Activated Protein Kinases/metabolism , Liver/drug effects , Liver/enzymology , Liver/pathology , Male , Membrane Proteins/metabolism , Organometallic Compounds/pharmacokinetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Protein Processing, Post-Translational/drug effects , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Signal Transduction , Unfolded Protein Response/drug effects , Water Pollutants, Chemical/pharmacokinetics , Water Pollutants, Chemical/toxicity
3.
J Evol Biol ; 25(3): 438-51, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22239387

ABSTRACT

In Tribolium flour beetles and other organisms, individuals migrate between heterogeneous environments where they often encounter markedly different nutritional conditions. Under these circumstances, theory suggests that genotype-by-environment interactions (GEI) may be important in facilitating adaptation to new environments and maintaining genetic variation for male traits subject to directional selection. Here, we used a nested half-sib breeding design with Tribolium castaneum to partition the separate and joint effects of male genotype and nutritional environment on phenotypic variation in a comprehensive suite of life-history traits, reproductive performance measures across three sequential sexual selection episodes, and fitness. When male genotypes were tested across three nutritional environments, considerable phenotypic plasticity was found for male mating and insemination success, longevity and traits related to larval development. Our results also revealed significant additive genetic variation for male mating rate, sperm offence ability (P(2)), longevity and total fitness and for several traits reflecting both larval and adult resource use. In addition, we found evidence supporting GEI for sperm defence ability (P(1)), adult longevity and larval development; thus, no single male genotype outperforms others in every nutritional environment. These results provide insight into the potential roles of phenotypic plasticity and GEI in facilitating Tribolium adaptation to new environments in ecological and evolutionary time.


Subject(s)
Animal Nutritional Physiological Phenomena/physiology , Environment , Phenotype , Reproduction/physiology , Sex Characteristics , Tribolium/genetics , Analysis of Variance , Animals , Genetic Fitness/genetics , Genetic Variation , Genotype , Longevity/physiology , Male , Reproduction/genetics , Sexual Behavior, Animal/physiology , Spermatozoa/physiology , Tribolium/physiology
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