title: Tetrahydrocurcumin in combination with deferiprone attenuates hypertension, vascular dysfunction, baroreflex dysfunction, and oxidative stress in iron-overloaded mice.
abstract: Excessive iron can generate reactive oxygen species (ROS), leading to oxidative stress that is closely associated with cardiovascular dysfunction. Iron overload was induced in male ICR mice by injection of iron sucrose (10mg/kg/day) for eight weeks. Iron overload was evidenced by increased serum iron indices. The mice developed increased blood pressure, impaired vascular function and blunted response of the autonomic nervous system. These effects were accompanied by increased malondialdehyde levels in various tissues, increased nitric oxide metabolites in plasma and urine, and decreased blood glutathione. Tetrahydrocurcumin (THU, 50mg/kg/day), deferiprone (or L1, 50mg/kg/day) or both was orally administered throughout the period of iron sucrose injection. The treatments significantly alleviated the deleterious cardiovascular effects of iron overload, and were associated with modulation of nitric oxide levels. An imbalance between endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) expression in response to iron overload was normalized by THU, L1 or the combination treatment. Moreover, the treatment decreased the upregulated expression levels of gp91phox, p47phoxand HO-1. The combination of THU and L1 exerted a greater effect than THU or L1 monotherapy. These results suggest beneficial effects of THU and L1 on iron-induced oxidative stress, hypertension, and vascular dysfunction.
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: 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: Department of Physical Therapy, Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Wanida
authors.initials: W
authors.lastname: Donpunha
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibahara
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: upa_ku@kku.ac.th.
authors.forename: Upa
authors.initials: U
authors.lastname: Kukongviriyapan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077543:Deferiprone; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005290:Ferric Compounds / Q000008:administration & dosage; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology; D019190:Iron Overload / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D005290:Ferric Compounds; D007502:Iron Chelating Agents; D011728:Pyridones; C096277:tetrahydrocurcumin; D000077543:Deferiprone; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000077605:Ferric Oxide, Saccharated; D003474:Curcumin; D005937:Glucaric Acid
keywords: Baroreflex sensitivity; Deferiprone; Iron overload; Tetrahydrocurcumin; Vascular dysfunction