Tetrahydrocurcumin Protects against Cadmium-Induced Hypertension, Raised Arterial Stiffness and Vascular Remodeling in Mice

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.

Cadmium Toxicity: Oxidative Stress, Inflammation and Tissue Injury

“…Also reported in the study was the crosslinking of myofibrillar collagen fibers forming an irregular branching pattern and complicated matrix network [90]. In addition to the cardiac tissues, Cd alters the aorta's histological integrity as evidenced by the induction of hypertrophic aortic wall remodeling by hyperplasia of smooth muscle cells, increased collagen deposition, decreased elastin and increased aortic medial wall matrix metalloproteinases [91]. Another study evaluating the histopathological changes in the heart of male albino rats treated with 200 mg/L Cd for 8 weeks reported focal hyaline degeneration and perivascular fibrosis with narrowed lumen of cardiac blood vessels after 4 weeks, hyaline degeneration with focal areas of coagulative necrosis and interstitial fibrosis in the left ventricle after 8 weeks [92].…”

Cadmium-induced endothelial dysfunction mediated by asymmetric dimethylarginine

“…In vitro experiments on endothelial cells have shown that Cd concentrations at low doses, below the currently considered toxic level, lead to increased cell permeability due to cell death (Messner et al 2009;Pérez Díaz et al 2013). Sangartit et al (2014) reported the thickening and stiffening of the aortic wall in Cd-exposed mice which were associated with alterations in the vascular composition. Similar outcomes are also reflected in the current study suggesting altered mechanical forces during exposure to Cd that may be triggered by adaptive restructuring of the aorta.…”

Oxidative Stress and Cardiovascular Dysfunction Associated with Cadmium Exposure: Beneficial Effects of Curcumin and Tetrahydrocurcumin

“…We proposed that Cd content in the aorta might induce aortic weakening through the adverse effects on smooth muscle cell metabolism and the attenuation of vascular reactivity to vasoactive agents. A combination of these effects results from long-term damage of endothelial and vascular smooth muscle cells caused by Cd intoxication Sangartit et al 2014). We also found that Cd promotes vascular smooth muscle growth and proliferation, enhances vascular remodeling, and increases arterial stiffening ).…”