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Weerapon Sangartit Upa Kukongviriyapan Wanida Donpunha Poungrat Pakdeechote Veerapol Kukongviriyapan Praphassorn Surawattanawan Stephen E. Greenwald 《PloS one》2014,9(12)
Background
Cadmium (Cd) is a nonessential heavy metal, causing oxidative damage to various tissues and associated with hypertension. Tetrahydrocurcumin (THU), a major metabolite of curcumin, has been demonstrated to be an antioxidant, anti-diabetic, anti-hypertensive and anti-inflammatory agent. In this study, we investigated the protective effect of THU against Cd-induced hypertension, raised arterial stiffness and vascular remodeling in mice.Methods
Male ICR mice received CdCl2 (100 mg/l) via drinking water for 8 weeks. THU was administered intragastrically at dose of 50 or 100 mg/kg/day concurrently with Cd treatment.Results
Administration of CdCl2 significantly increased arterial blood pressure, blunted vascular responses to vasoactive agents, increased aortic stiffness, and induced hypertrophic aortic wall remodeling by increasing number of smooth muscle cells and collagen deposition, decreasing elastin, and increasing matrix metalloproteinase (MMP)-2 and MMP-9 levels in the aortic medial wall. Supplementation with THU significantly decreased blood pressure, improved vascular responsiveness, and reversed the structural and mechanical alterations of the aortas, including collagen and elastin deposition. The reduction on the adverse response of Cd treatment was associated with upregulated eNOS and downregulated iNOS protein expressions, increased nitrate/nitrite level, alleviated oxidative stress and enhanced antioxidant glutathione. Moreover, THU also reduced the accumulation of Cd in the blood and tissues.Conclusions
Our results suggest that THU ameliorates cadmium-induced hypertension, vascular dysfunction, and arterial stiffness in mice through enhancing NO bioavailability, attenuating oxidative stress, improving vascular remodeling and decreasing Cd accumulation in other tissues. THU has a beneficial effect in moderating the vascular alterations associated with Cd exposure. 相似文献2.
Wanida Donpunha Upa Kukongviriyapan Kwanjit Sompamit Poungrat Pakdeechote Veerapol Kukongviriyapan Patchareewan Pannangpetch 《Biometals》2011,24(1):105-115
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 CdCl2 (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. 相似文献
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