Abstract

Recently, the addition of copper nanoparticles (NPs) in a daily diet (6.5 mg/kg) was studied in different animal models as a possible alternative to ionic forms. Male Wistar–Kyoto rats (24-week-old, n = 11) were fed with copper, either in the form of carbonate salt (Cu6.5) or metal-based copper NPs (NP6.5), for 8 weeks. The third group was fed with a half dose of each (NP3.25 + Cu3.25). The thoracic aorta and blood plasma was studied. Supplementation with NP6.5 decreased the Cu (×0.7), Cu/Zn-ratio (×0.6) and catalase (CAT, ×0.7), and increased Zn (×1.2) and superoxide dismutase (SOD, ×1.4). Meanwhile, NP3.25 + Cu3.25 decreased the Cu/Zn-ratio (×0.7), and CAT (×0.7), and increased the daily feed intake (×1.06). Preincubation with either the selective cyclooxygenase (COX)-2 inhibitor, or the non-selective COX-1/2 inhibitor attenuated vasodilation of rat thoracic aorta in the NP6.5 group exclusively. However, an increased vasodilator response was observed in the NP6.5 and NP3.25 + Cu3.25 group of rats after preincubation with an inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) formation, and the thromboxane receptor (TP) antagonist. Significant differences were observed between the NP6.5 and NP3.25 + Cu3.25 groups of rats in: dietary intake, acetylcholine-induced vasodilation, and response to COX-inhibitors. Copper NPs in a standard daily dose had more significant effects on the mechanism(s) responsible for the utilization of reactive oxygen species in the blood plasma with the participation of prostanoids derived from COX-2 in the vascular relaxation. Dietary copper NPs in both doses modified vasodilation through the vasoconstrictor 20-HETE and the TP receptors.

Highlights

  • Licensee MDPI, Basel, Switzerland.Copper fluctuations in a diet may have either pro- or antioxidant effects on animal or human health, dependent on the daily dose [1,2,3,4]

  • Acetylcholine, indomethacin, noradrenaline, and NS-398 were obtained from Sigma-Aldrich

  • W/v) solution; HET0016, SQ-29,548, and indomethacin were dissolved in ethanol; 1400 W in methanol; and NS-398 in DMSO

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Summary

Introduction

Licensee MDPI, Basel, Switzerland.Copper fluctuations in a diet may have either pro- or antioxidant effects on animal or human health, dependent on the daily dose [1,2,3,4]. Cytochrome c oxidase, lysyl oxidase, L-ascorbate oxidase, monoamine oxidase, tyrosinase, and the enzymes of tryptophan degradation [7]. This may bring oxidative damage to lipids, proteins, and DNA, and result in neurodegenerative changes when dysregulated by either copper deficiency or its surplus [8,9]. Copper NPs induce a toxic effect by the increased production of free radicals, including hydroxyl radicals, hydrogen peroxides, and superoxide anions. The properties of metal NPs, including small size and high reactivity, increase their biological action, which may interfere with the physiological processes and the bioavailability of other macro- and microelements; the standard daily dose (6.5 mg/kg of diet) should probably be reduced to prevent increased toxicity [11]

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