The interaction between resveratrol and two forms of copper as carbonate and nanoparticles on antioxidant mechanisms and vascular function in Wistar rats

Pharmacol Rep. 2019 Oct;71(5):862-869. doi: 10.1016/j.pharep.2019.03.011. Epub 2019 Mar 23.

Abstract

Background: Experimental studies have emphasized that cardiovascular alterations can be improved by the long-term use of resveratrol (trans-3,5,4'-trihydroxystilbene; RSV) as well as dietary copper (Cu) intake.

Methods: Male Wistar rats were supplemented for 8 weeks with Cu (6.5 mg/kg diet) as either nanoparticles (40 nm, CuNPs) or carbonate (CuCO3). Half of the studied animals were supplemented with RSV (500 mg/kg diet). Vascular function and blood plasma antioxidant status, expressed as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), lipid hydroperoxides (LOOH) and malondialdehyde (MDA) were analyzed. The activity of ceruloplasmin (Cp), lipid profile, fasting glucose, and concentrations of Cu and zinc (Zn) were analyzed.

Results: RSV supplementation resulted in the elevated activity of SOD and decreased CAT, GPx and LDL-cholesterol in both groups. RSV supplementation on CuNPs increased the participation of vasoconstrictor prostanoids and decreased ACh-induced vasodilation, while the participation of hyperpolarizing mechanism(s) was restored by activating KATP channels. Blood plasma glucose was decreased. RSV supplementation on CuCO3 enhanced ACh- and SNP-induced vasodilation and decreased NA-induced vasoconstriction. The lipid profile was improved, as well as Zn concentration. Meanwhile, Cu and Cp, and the markers of lipid peroxidation, reflected as LOOH and MDA, were decreased.

Conclusion: The use of RSV during CuCO3 intake improves vascular responses, the lipid profile and the antioxidant mechanism(s). The beneficial role of RSV was not observed in the CuNP group and decreased ACh-induced vasodilation and increased participation of vasoconstrictor prostanoids in the vascular regulation were noticed.

Keywords: Antioxidant status; Copper nanoparticles; Potassium channels; Resveratrol; Thoracic aorta.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / metabolism
  • Carbonates / chemistry
  • Carbonates / pharmacology*
  • Ceruloplasmin / analysis
  • Copper / chemistry
  • Copper / pharmacology*
  • Drug Interactions
  • Lipid Peroxidation / drug effects
  • Lipids / blood
  • Male
  • Nanoparticles / chemistry*
  • Rats, Wistar
  • Resveratrol / chemistry
  • Resveratrol / pharmacology*
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects

Substances

  • Antioxidants
  • Carbonates
  • Lipids
  • Copper
  • copper carbonate
  • Ceruloplasmin
  • Resveratrol