title: [Disorder of copper homeostasis induced by lead exposure among mice and intervention effect of quercetin].
abstract: OBJECTIVE
  To investigate the effect of lead exposure on copper and copper metalloenzyme and the intervention effect of quercetin.
  
  
  METHODS
  Twenty-four specific pathogen-free male Sprague-Dawley rats of good health were randomly divided into control group (n = 8), lead acetate group (n = 8), and lead acetate + quercetin group (n = 8). The rats in lead acetate group were poisoned by drinking water with 1 g/L lead acetate for 8 weeks, while the rats in control group were fed by drinking water with sodium acetate of the same volume for 8 weeks; the rats in lead acetate+quercetin group were intraperitoneally injected with quercetin (30 mg × kg-1 × d-1) for 8 weeks while drinking water with lead acetate. The Morris water maze was used to test the learning and memory abilities of rats. The lead and copper levels in the serum, hippocampus, cortex, and bone were measured by graphite furnace atomic absorption spectrometry. The level of advanced glycation end products, activity of Cu/Zn superoxide dismutase (SOD), and content and activity of ceruloplasmin (CP) in the hippocampus and serum were measured using a test kit. HE staining was performed to observe the pathological changes in the hippocampus.
  
  
  RESULTS
  The Morris water maze test showed that the latency in lead acetate group (52.50±12.04 s) was significantly longer than that in control group (28.08±7.31 s) (P<0.05), and the number of platform crossings was significantly lower in the lead acetate group than in the control group. Compared with those in the control group, the lead levels in the cortex and hippocampus in lead acetate group increased 2.72-fold and 3.79-fold, and the copper in the cortex and hippocampus, and serum free copper levels in lead acetate group increased 1.15-fold, 1.48-fold, and 6.44-fold. Compared with the control group, the lead acetate group had a lower content of CP in the hippocampus (1.23±0.40 U/mg provs0.78±0.08 U/mg pro) and 31.81%and 19.49%decreases in CP content and Cu/Zn SOD activity. Free copper level in serum was positively correlated with the latency and lead levels in the serum, cortex, and hippocampus. The escape latency of rats in lead acetate + quercetin group was decreased by 42.15% (P<0.05). The lead levels in the cortex and hippocampus in lead acetate + quercetin group (0.246 ± 0.58 µg/g and 0.202±0.049 µg/g) were significantly lower than those in lead acetate group (0.391±0.49 µg/g and 0.546±0.120 µg/g), but the free copper and copper levels in the hippocampus and cortex were not significantly reduced. The lead acetate + quercetin group had higher Cu/Zn SOD activity and CP content in the hippocampus than the lead acetate group (P < 0.05). The light microscope observation showed that the number of cells in the hippocampus was reduced with disordered arrangement in the lead acetate group; with quercetin intervention, the hippocampus damage was reduced.
  
  
  CONCLUSIONS
  Lead exposure results in disorder of copper homeostasis, while quercetin may alleviate the damage induced by lead to some extent.
authors.affiliation: Department of Toxicology, School of Public Health, Hebei United University, Tangshan, Hebei Province 063000, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Li-cheng
authors.initials: LC
authors.lastname: Yan
authors.forename: Fu-yuan
authors.initials: FY
authors.lastname: Cao
authors.forename: Hui-xin
authors.initials: HX
authors.lastname: Zhao
authors.forename: Ya-jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Guo
authors.forename: Wei-jing
authors.initials: WJ
authors.lastname: Meng
authors.forename: Qing-zhao
authors.initials: QZ
authors.lastname: Li
authors.forename: Yan-shu
authors.initials: YS
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry; D003300:Copper / Q000097:blood*; D006624:Hippocampus / Q000737:chemistry; D006706:Homeostasis; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009942:Organometallic Compounds / Q000633:toxicity*; D011794:Quercetin / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D009942:Organometallic Compounds; D003300:Copper; D011794:Quercetin; D013482:Superoxide Dismutase; C008261:lead acetate