Abstract
BackgroundCadmium (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.MethodsMale 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.ResultsAdministration 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.ConclusionsOur 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.
Highlights
Cd, in its ionic form (Cd2+), is a highly toxic metal that is widely distributed in the environment
Phenylephrine (Phe), thiobarbituric acid (TBA), 5,5 dithio-bis-2-nitrobenzoic acid (DTNB), ethylenediamine tetraacetic acid (EDTA), sodium dodecyl sulfate (SDS), glutathione (GSH), butylated hydroxytoluene (BHT), sulfanilamide, dinitrophenylephrinenylhydrazine (DNPH), N-1-nepthylethylenediamine dihydrochloride (NED), 1,1,3,3-tetraethoxypropane, bromophenol blue, 2-mercaptoetanol, lucigenin and guanidine were purchased from Sigma-Aldrich Pte
The major findings of this study are that Cd exposure induces hypertension, vascular dysfunction and vascular stiffening by remodeling of the vascular scleroproteins and increased oxidative stress
Summary
In its ionic form (Cd2+), is a highly toxic metal that is widely distributed in the environment. Previous studies suggest that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are important intracellular signaling molecules that regulate vascular function by modulating vascular cell contraction/dilation, growth/apoptosis, migration, and extracellular matrix protein turnover. All of these factors contribute to vascular remodeling and stiffening [20]. 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. The reduction on the adverse response of Cd treatment was associated with upregulated eNOS and downregulated iNOS protein expressions, increased nitrate/nitrite level, alleviated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
