title: Tetrahydrocurcumin protects against cadmium-induced hypertension, raised arterial stiffness and vascular remodeling in mice.
abstract: 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.
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Weerapon
authors.initials: W
authors.lastname: Sangartit
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Upa
authors.initials: U
authors.lastname: Kukongviriyapan
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Wanida
authors.initials: W
authors.lastname: Donpunha
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Poungrat
authors.initials: P
authors.lastname: Pakdeechote
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Veerapol
authors.initials: V
authors.lastname: Kukongviriyapan
authors.affiliation: Research and Development Institute, The Government Pharmaceutical Organization, Rama VI Road, Ratchathewi, Bangkok 10400, Thailand.
authors.forename: Praphassorn
authors.initials: P
authors.lastname: Surawattanawan
authors.affiliation: Pathology Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 1BB, United Kingdom.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Greenwald
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000008:administration & dosage*; D066253:Vascular Remodeling / Q000187:drug effects; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D020011:Protective Agents; D002104:Cadmium; C096277:tetrahydrocurcumin; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D003474:Curcumin