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Copper nanoparticles modify the blood plasma antioxidant status and modulate the vascular mechanisms with nitric oxide and prostanoids involved in Wistar rats

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Abstract

Background

We aimed to analyze whether a diet supplemented with a standard dose of copper (Cu) in the form of nanoparticles, as an alternative to carbonate, exerts beneficial effects within the vasculature and improves the blood antioxidant status.

Methods

Male Wistar rats were fed for 8 weeks with a diet supplemented with Cu (6.5 mg Cu/kg in the diet) either as nanoparticles (40 nm diameter) or carbonate — the control group. Moreover, a negative control was not supplemented with Cu. At 12 weeks of age, blood samples, internal organs and thoracic aorta were taken for further analysis. Blood antioxidant mechanism was measured together with Cu and Zn.

Results

Diet with Cu as nanoparticles resulted in an elevated catalase activity and ferric reducing ability of plasma, however decreased Cu (plasma), and ceruloplasmin (Cp) compared to carbonate. The participation of vasoconstrictor prostanoid was increased, as indomethacin did not modify the acetylcholine (ACh)-induced response. Arteries from Cu nanoparticle and carbonate rats exhibited a reduced maximal contraction to potassium chloride and an increased response to noradrenaline. The endothelium-dependent vasodilation to ACh was enhanced while exogenous NO donor, sodium nitroprusside, did not modify the vascular response. Down-regulation of BKCa channels influenced hyperpolarizing mechanism. The superoxide dismutase and HDL-cholesterol were decreased opposite to an increased lipid hydroperoxides, malondialdehyde, Cu (plasma and liver) and Cp.

Conclusion

Despite the increased antioxidant capacity in blood of Cu nanoparticle fed rats, vasoconstrictor prostanoids and NO are involved in vascular regulation.

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Abbreviations

ACh:

acetylcholine

ANOVA:

analysis of variance

CAT:

catalase

CCRC:

cumulative concentration-response curve

COX:

cyclooxygenase

Cp:

ceruloplasmin

Cu:

copper

CuD:

copper deficient

CuNPs:

copper nanoparticles

Emax:

maximal response values

FRAP:

ferric reducing antioxidant power

HDL:

high density lipoprotein

K+:

potassium

KATP:

ATP-dependent potassium channels

KCa:

calcium-dependent potassium channels

KHS:

Krebs-Henseleit solution

LDL:

low density lipoprotein

L-NAME:

Nω-Nitro-L arginine methyl ester

LOOH:

lipid hydroperoxides

MDA:

malondialdehyde

NA:

noradrenaline

NO:

nitric oxide

NOS:

nitric oxide synthase

pD2:

drug concentration exhibiting 50% of the Emax expressed as negative log molar

ROS:

reactive oxygen species

SEM:

standard error of the mean

SNP:

sodium nitroprusside

SOD:

superoxide dismutase

TG:

triglycerides

Zn:

zinc

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Medicine, University of Warmia and Mazury, Olsztyn, Poland

    Michał Majewski

  2. Department of Biochemistry and Toxicology, Faculty of Biology, Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, Lublin, Poland

    Katarzyna Ognik

  3. Division of Food Science, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland

    Jerzy Juśkiewicz

Authors
  1. Michał Majewski
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  2. Katarzyna Ognik
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  3. Jerzy Juśkiewicz
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Correspondence to Michał Majewski.

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Majewski, M., Ognik, K. & Juśkiewicz, J. Copper nanoparticles modify the blood plasma antioxidant status and modulate the vascular mechanisms with nitric oxide and prostanoids involved in Wistar rats. Pharmacol. Rep 71, 509–516 (2019). https://doi.org/10.1016/j.pharep.2019.02.007

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