Efeitos do hidrolisado da clara do ovo sobre as artérias mesentéricas de ratos expostos cronicamente ao cloreto de Mercúrio (HgCl2)

Abstract

Egg white hydrolyzate (HCO) has antioxidant, anti-inflammatory and vasodilatory properties and can be an efficient alternative for the prevention or treatment of heavy metal poisoning. The objective was to investigate the potential beneficial effects of HCO ingestion in vascular reactivity disorders induced by chronic exposure to low Hg concentrations in mesenteric resistance arteries (ARM), as well as to clarify the possible pathways involved in its effects. Male Wistar rats were divided into four groups, treated for 60 days with: a) intramuscular injections (i.m.) of 0.9% saline and water by gavage (Untreated Group); b) i.m. injections of mercury chloride - HgCl2, the first dose 4.6 μg / kg and subsequent doses of 0.07 μg / kg / day, to cover daily loss, using the model previously described (Rizzetti et al., 2017a) and gavage water (HgCl2 Group); c) i.m. injections of 0.9% saline solution and HCO (obtained by hydrolysis by pepsin for 8 hours) diluted in water (1 g / kg / day), by gavage, according to a previously reported model (Rizzetti et al., 2016a) (HCO Group ); d) both treatments (HCO + HgCl2). Systolic blood pressure (SBP) was assessed, vascular function was studied in ARM in an isolated organ bath. Concentration-response curves for acetylcholine (ACh) and sodium nitroprusside (NPS) were performed. Vasoconstrictor response to noradrenaline (NE) in the presence and absence of endothelium and in the presence of an inhibitor of the enzyme nitric oxide synthase (NOS) (L-NAME), a non-selective inhibitor of cyclooxygenase (COX) (INDO), a cofactor essential for the synthesis of NO (BH4), a NADPH oxidase inhibitor (VAS2870) and a superoxide dismutase mimetic (TEMPOL) were analyzed. We measure in situ production of superoxide anion, NO release, reactive vascular oxygen species (ROS), lipid peroxidation, antioxidant capacity and NPSH levels in ARM. The study was approved by the Ethics Committee on Animal Use (052014 - Unipampa). The results were expressed as mean ± SEM, compared by one-way or two-way ANOVA analysis followed by Fisher's post hoc test. (P <0.05). Co-treatment with HCO: a) prevented an increase in SBP, endothelial dysfunction and an increase in the vasoconstrictor response to NE promoted by prolonged exposure to HgCl2 in ARM; b) restored NO-mediated endothelial modulation; c) inhibited the oxidative stress derived from NAD (P) H oxidase and the inflammatory pathways induced by the metal in these vessels, normalizing the antioxidant state. We conclude that HCO appears to be able to neutralize the toxic vascular effects of long-term exposure to HgCl2, which points to possible therapeutic effects based on functional food against a highly widespread environmental contaminant.