Vascular Hyperpermeability Response in Animals Systemically Exposed to Arsenic

Abstract

The mechanisms underlying cardiovascular diseases induced by chronic exposure to arsenic remain unclarified. The objectives of this study were to investigate whether increased vascular leakage is induced by inflammatory mustard oil in mice systemically exposed to various doses of arsenic and whether an increased vascular leakage response is still present in arsenic-fed mice after arsenic discontinuation for 2 or 6 months. ICR mice were fed water or various doses of sodium arsenite (10, 15, or 20 mg/kg/day; 5 days/week) for 8 weeks. In separate experiments, the mice were treated with sodium arsenite (20 mg/kg) for 2 or 8 weeks, followed by arsenic discontinuation for 2 or 6 months. Vascular permeability to inflammatory mustard oil was quantified using Evans blue (EB) techniques. Both arsenic-exposed and water-fed (control) mice displayed similar basal levels of EB leakage in the ears brushed with mineral oil, a vehicle of mustard oil. The levels of EB leakage induced by mustard oil in the arsenic groups fed with sodium arsenite (10 or 15 mg/kg) were similar to those of water-fed mice. However, increased levels of EB leakage in response to mustard oil stimulation were significantly higher in mice treated with sodium arsenite (20 mg/kg; high dose) than in arsenic-fed (10 or 15 mg/kg; low and middle doses) or control mice. After arsenic discontinuation for 2 or 6 months, mustard oil-induced vascular EB leakage in arsenic-fed (20 mg/kg) mice was similar to that in control mice. Dramatic increases in mustard oil-induced vascular leakage were only present in mice systemically exposed to the high arsenic dose, indicating the synergistic effects of the high arsenic dose and mustard oil.

Coenzyme Q10 protected against arsenite and enhanced the capacity of 2,3-dimercaptosuccinic acid to ameliorate arsenite-induced toxicity in mice

“…Besides, the effectiveness of 200 mg/kg CoQ 10 as an anti-inflammatory and anti-oxidant agent has been demonstrated [ 25 ]. A dose of 15 mg/kg arsenite was chosen for this study based on the findings that 15 mg/kg is able to induce toxicity in wild type mice characterized by vascular permeability and increasing arsenic concentration in blood and tissues [ 26 , 27 ]. A dose of 50 mg/kg for 5 days was administered to mice exposed to sodium arsenite.…”

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

“…Zarazúa et al reported the effects of the detrimental effect of arsenic exposure on NO (nitric oxide) production, which is a critical modulator for endothelial function [154]. Arsenic-containing lipids also enhanced the permeability of the blood-brain barrier and may alter the arteriolar perfusion, hallmark characteristics of the small vessel disease [155,156]. Arsenic induced decrease in NO production was accompanied by significantly higher levels of lipid peroxidation and ROS production.…”