Protective effect of ascorbic acid on cadmium-induced hypertension and vascular dysfunction in mice

Abstract

Cadmium (Cd) is one of the most important environmental pollutants that cause a number of adverse health effects in humans and animals. Recent studies have shown that Cd-induced oxidative damage within the vascular tissues results in vascular dysfunction. The current study was aimed to investigate whether ascorbic acid could protect against Cd-induced vascular dysfunction in mice. Male ICR mice were received CdCl(2) (100 mg/l) via drinking water for 8 weeks alone or received ascorbic acid supplementation at doses of 50 and 100 mg/kg/day for every other day. Results showed that Cd administration increased arterial blood pressure and blunted the vascular responses to vasoactive agents. These alterations were related to increased superoxide production in thoracic aorta, increased urinary nitrate/nitrite, increased plasma protein carbonyl, elevated malondialdehyde (MDA) concentrations in plasma and tissues, decreased blood glutathione (GSH), and increased Cd contents in blood and tissues. Ascorbic acid dose-dependently normalized the blood pressure, improved vascular reactivities to acetylcholine (ACh), phenylephrine (Phe) and sodium nitroprusside (SNP). These improvements were associated with significant suppression of oxidant formation, prevention of GSH depletion, and partial reduction of Cd contents in blood and tissues. The findings in this study provide the first evidence in pharmacological effects of ascorbic acid on alleviation of oxidative damage and improvement of vascular function in a mouse model of Cd-induced hypertension and vascular dysfunction. Moreover, our study suggests that dietary supplementation of ascorbic acid may provide beneficial effects by reversing the oxidative stress and vascular dysfunction in Cd-induced toxicity.

Environmental factors in cardiovascular disease

“…215 Cadmium can contribute to atherosclerosis indirectly through hypertension and renal effects. Experimental studies have led to reports of persistent blood-pressure elevations associated with cadmium exposures, 216 which is consistent with the results of some 209 -but not all 217 -epidemiological studies. With respect to kidney disease, increasing, chronic, low-level cadmium exposure has been associated with higher rates of kidney dialysis and transplantation, 218 albuminuria, 219 and proximal tubular dysfunction, 220,221 and with lower estimated glomerular f iltration rate, independent of risk factors for kidney disease.…”

Spices Mixture Containing Garlic, Ginger and Nutmeg Has Protective Effects on the Kidneys and Liver of Cadmium Exposed Rats

“…[1][2][3][4][5][6] It has been proposed that Cadmium mediates its cytotoxicity via several mechanisms including induction of apoptosis, ischemia, inflammation and oxidative stress. 4,5 Compelling evidence also suggests that cadmium may cause toxicity by displacing important divalent metals ions such as zinc, selenium, calcium, and copper from their binding site.…”

Endothelial dysfunction in subjects with chronic cadmium exposure

“…In vitro exposure of endothelial cells to Cd (15 μM) resulted in the increased permeability, inhibition of cell proliferation and induction of cell death (Messner et al, 2009). Cd induced hypertension in rats, which involved oxidative stress and suppression of eNOS expression in blood vessels leading to impaired acetylcholineinduced vasorelaxation (Yoopan et al, 2008;Donpunha et al, 2011). Rats treated with Cd had increased response to vasopressor phenylephrine, and increased expression of NADPH oxidase in endothelial cells (Almenara et al, 2013).…”