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The most commonly used indices for determining copper deficiency in humans are reduced serum/ plasma copper concentration and decreased activity of ceruloplasmin and Cu/Zn superoxide dismutase (SOD1). However, these indicators are influenced by many factors unrelated to copper status and lack the sensitivity required to detect marginal deficiency, limiting their usefulness in many situations. In vivo, the insertion of copper into SOD1 is dependent on the copper chaperone for SOD1 (CCS). In this study, we explored the possibility that the expression level of CCS may reflect copper status and thus serve as a useful marker of copper nutriture. Weanling male Wistar rats were fed either a normal (5.3 mg Cu/kg diet), moderately deficient (0.84 mg Cu/kg diet) or deficient (0.34 mg Cu/kg diet) copper diet for 6 wk. Rats fed moderate and deficient diets showed differences (P < 0.05) in several hematological measurements, indicating varying degrees of copper deficiency in these groups. Copper-deficient rats had reduced (P < 0.05) liver and erythrocyte SOD1 activity and body weight. Western blot analysis revealed a dose-dependent increase (P < 0.05) in CCS expression in liver and erythrocytes of copper-deficient rats. We report CCS protein level as a novel marker for assessing copper status. KEY WORDS: * copper status * copper chaperone * Cu/Zn superoxide dismutase * expression level * rats

Abstract Background Selenium (Se), vitamin C and vitamin E function as antioxidants within the body. In this study, we investigated the effects of reduced dietary Se and L-ascorbic acid (AA) on vitamin C and α-tocopherol (AT) status in guinea pig tissues. Methods Male Hartley guinea pigs were orally dosed with a marginal amount of AA and fed a diet deficient (Se-D/MC), marginal (Se-M/MC) or normal (Se-N/MC) in Se. An additional diet group (Se-N/NC) was fed normal Se and dosed with a normal amount of AA. Guinea pigs were killed after 5 or 12 weeks on the experimental diets at 24 and 48 hours post AA dosing. Results Liver Se-dependent glutathione peroxidase activity was decreased (P < 0.05) in guinea pigs fed Se or AA restricted diets. Plasma total glutathione concentrations were unaffected (P > 0.05) by reduction in dietary Se or AA. All tissues examined showed a decrease (P < 0.05) in AA content in Se-N/MC compared to Se-N/NC guinea pigs. Kidney, testis, muscle and spleen showed a decreasing trend (P < 0.05) in AA content with decreasing Se in the diet. Dehydroascorbic acid concentrations were decreased (P < 0.05) in several tissues with reduction in dietary Se (heart and spleen) or AA (liver, heart, kidney, muscle and spleen). At week 12, combined dietary restriction of Se and AA decreased AT concentrations in most tissues. In addition, restriction of Se (liver, heart and spleen) and AA (liver, kidney and spleen) separately also reduced AT in tissues. Conclusion Together, these data demonstrate sparing effects of Se and AA on vitamin C and AT in guinea pig tissues.

Abstract Background Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status. Methods Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status. Results Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4). Conclusion Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn.