Name: FILIPE MARTINUZO FILETTI
Publication date: 13/05/2022
Advisor:
Name |
Role |
|---|---|
| MAYLLA RONACHER SIMÕES | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| ALESSANDRA SIMAO PADILHA | Internal Examiner * |
| GIULIA ALESSANDRA WIGGERS PECANHA | External Examiner * |
| MAYLLA RONACHER SIMÕES | Advisor * |
| NAZARE SOUZA BISSOLI | Internal Examiner * |
Summary: Copper (Cu) is an essential element for homeostasis and the functioning of living organisms, but in excess it promotes systemic harmful effects. According to regulatory agencies, copper consumption should be 0.9 mg/day for adults, with 10 mg/day being considered the maximum tolerable dose in humans. Copper toxicity is related to the production of Reactive Oxygen Species (ROS), leading to the occurrence of cardiovascular diseases. In this context, the bioactive peptides derived from the egg white hydrolyzate (EWH) have important antioxidant activity, neutralizing free radicals, and anti-inflammatory activity, which can act in several diseases. We aimed to evaluate the cardiovascular effects of exposure to the recommended daily dose (13 μg/Kg/day), the maximum tolerable intake dose (0.14 mg/Kg/day) and twice the tolerable dose (0.28 mg/Kg/day) of copper for 4 weeks and then assess whether EWH consumption is able to attenuate these effects. We evaluated the effects of copper in the following experimental groups: Cu 0.13 μg/Kg/day, Cu 0.14 mg/Kg/day and Cu 0.28 mg/kg/day, via i.p. for 4 weeks, the Ct group received 0.9% saline via i.p. Our results showed that exposure to doses of 13 μg, 0.14 and 0.28 mg/Kg/day of copper did not change body weight gain, vascular reactivity and did not change the mass of cardiac chambers, however we identified that exposure to doses of copper 0.14 and 0.28 mg/Kg/day of copper reduced the force of contraction of papillary muscles and impaired cardiac contraction regulatory mechanisms such as temporal force derivatives, inotropic response to extracellular calcium and isoproterenol, indirect assessment of transsarcolemmal calcium influx and contractile protein affinity. Although the dose of 0.14 mg/Kg/day of copper is considered safe, our results showed harm caused by this exposure, so we determined this dose to assess whether EWH could prevent these effects, so we performed these studies again with the following groups: Ct, Cu, Ct-EWH and Cu-EWH. Treatment with EWH proved to be effective in preventing the toxic effects of copper. Exposure to copper and/or EWH did not alter the animals` systolic blood pressure, body weight gain and did not alter the mass of the cardiac chambers. The consumption of EWH in animals exposed to copper prevented the reduction of the force of cardiac contraction, of the temporal derivatives of force, of the inotropic response to calcium and to Isoproterenol, of the indirect
evaluation of the transsarcolemmal calcium influx. Myosin ATPase activity was reduced by copper exposure, however this effect was reversed by EWH consumption. The in situ detection showed an increase of O2- and OH in the papillary muscles of animals that received copper, while the animals that received copper and EWH showed formation of free radicals similar to the controls. EWH increased the activity of the antioxidant enzymes SOD and catalase in control and copper exposed animals. The expressions of SOD, Catalase and NCX were not altered, the expression of SERCA-2a increased in the Cu-EWH group. We conclude that EWH can be considered a functional food ingredient to be used as a therapeutic tool in the treatment of damage induced by copper exposure.
