Cardiovascular Harmful Effects of Recommended Daily Doses (13 µg/kg/day), Tolerable Upper Intake Doses (0.14 mg/kg/day) and Twice the Tolerable Doses (0.28 mg/kg/day) of Copper

Abstract

Copper is essential for homeostasis and regulation of body functions, but in excess, it is a cardiovascular risk factor since it increases oxidative stress. The objective of this study was to evaluate the effects of exposure to the recommended daily dose (13 µg/kg/day), upper tolerable dose (0.14 mg/kg/day) and twice the upper tolerable dose (0.28 mg/kg/day) via i.p. over 4 weeks on the vascular reactivity of aortic rings and the contraction of LV papillary muscles. It was also determined whether the antioxidant peptide from egg white hydrolysate (EWH) prevents these effects. Copper exposure at the doses evaluated did not change weight gain, the reactivity of the aortic rings or the cardiac mass. The dose of 0.13 µg/kg/day did not reduce the force of contraction, but it impaired the time derivatives of force. Doses of 0.14 and 0.28 mg/kg/day reduced the force of contraction, the inotropic response to calcium and isoproterenol, the postrest contraction and the peak and plateau of tetanized contractions. EWH treatment antagonized these effects. These results suggest that copper, even at the dose described as upper tolerable, can impair cardiac contraction without altering vascular reactivity. Antioxidative stress therapy with EWH reversed these harmful effects, suggesting a possible strategy for the amelioration of these effects.

The Effect of an Elevated Dietary Copper Level on the Vascular Contractility and Oxidative Stress in Middle-Aged Rats

“…The findings of earlier research corroborate the information presented in this report [37]. In line with our findings, Filetti et al demonstrated that animals in both the control group and those that received varying doses of copper showed no significant differences in weight at the beginning and at the end of the treatment [38]. This is contrary to Banach et al, who found that excess body weight relates to an increased concentration of copper [39].…”

“…The Langendorff technique (the isolated perfused heart assay) was also not modified. Interestingly, Filetti et al suggested that copper administration over 4 weeks can impair cardiac contraction without altering vascular reactivity [ 38 ]. However, in this specific study, copper was injected via i.p.…”