Abstract
The current study was designed to investigate effect of copper administration on oxidative damage to the brain in ApoE−/− mice and to explore the putative neuroprotective effects rendered by apolipoprotein E (ApoE). Male C57BL/6 ApoE−/− and wild-type mice were randomly assigned into four groups, ApoE−/− mice wild-type mice treated with either copper or saline. Copper sulphate pentahydrate or saline (200 µl) were administered intragastrically daily for 12 weeks. Expression of malondialdehyde, superoxide dismutase (SOD), hemeoxygenase 1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) were determined by a combination of biochemical assays. The concentration of copper in the brain of C57BL/6 mice and ApoE−/− mice treated by copper significantly increased compared with mice treated by saline (P=0.0099 and P=0.0443). Compared with the C57BL/6 mice treated by copper, the level of the ApoE−/− mice treated by copper was higher (P=0.018). TBARS and SOD activities or the expressions of NQO1 and HO-1 in the brain were not significantly different amongst the four experimental groups of mice. The relative value of NQO1/β-actin expression in the brain of the ApoE−/− mice was similar in both saline and copper administration experimental groups. However, Western blot analysis showed that NQO1 expression was significantly higher in the ApoE−/− mice brain treated with saline compared with saline treated wild-type mice (P=0.0449). ApoE does not function in protecting the brain from oxidative damage resulting from copper build-up in Wilson’s disease, but may play a role in regulating copper accumulation in the brain.
Highlights
Hepatolenticular degeneration, termed as Wilson’s disease is an autosomal recessive genetic disorder and is characterized by ATP7B gene mutations, leading to defective copper metabolism [1]
The results showed that apolipoprotein E (ApoE)−/− mice treated with saline exhibited significantly higher copper concentrations in the brain compared with the wild-type mice treated with saline (4.3 +− 0.52 compared with 2.5 +− 0.43; P=0.0099)
Compared with the C57BL/6 mice treated by copper, the level of the ApoE−/− mice treated by copper was higher (5.2 +− 0.391 compared with 3.3 +− 0.21; P=0.018)
Summary
Hepatolenticular degeneration, termed as Wilson’s disease is an autosomal recessive genetic disorder and is characterized by ATP7B gene mutations, leading to defective copper metabolism [1]. Hepatic damage to various extents, neuropsychiatric symptoms, Kayser–Fleischer rings, and damage to the kidney and skeletal muscle are classical clinical hallmarks in Wilson’s disease. Liver damage is generally the major clinical manifestation at disease onset in children, whereas neurological symptoms tend to occur in those aged in their twenties or older [6]. The diversity of symptoms and differences in age at disease onset suggest that the features of this disease may not be determined exclusively by the ATP7B gene mutations and that other genetic factors may be involved in the pathogenesis and perhaps progression of the disease
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