title: Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats.
abstract: OBJECTIVE
  Cardiovascular disease (CVD) is common in chronic kidney disease (CKD) patients. Indoxyl sulfate (IS) is a nephrovascular uremic toxin that induces oxidative stress in kidney and vascular system. The present study aimed to examine the effect of IS on fibrosis and oxidative stress in rat heart.
  
  
  METHODS
  The effects of IS on heart were examined by Masson's trichrome (MT) staining and immunohistochemistry using: (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive IS-administered rats (DN+IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive IS-administered rats (DH+IS).
  
  
  RESULTS
  DH+IS rats showed significantly increased heart weight and left ventricle weight compared with DN. DH and DH+IS rats showed significantly increased diameter of cardiomyocytes, increased MT-positive fibrotic area, increased staining for transforming growth factor (TGF)-β1, α-smooth muscle actin (SMA), type 1 collagen, NADPH oxidase Nox 4, malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) and decreased staining for nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) in the heart compared with DN. More notably, DH+IS rats showed significantly increased diameter of cardiomyocytes, increased fibrotic area, increased staining for TGF-β1, SMA, type 1 collagen, Nox4, 8-OHdG and MDA, and decreased staining for Nrf2 and HO-1 in the heart compared with DH.
  
  
  CONCLUSIONS
  IS aggravates cardiac fibrosis and cardiomyocyte hypertrophy with enhanced oxidative stress and reduced anti-oxidative defense in hypertensive rats.
authors.affiliation: Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Maimaiti
authors.initials: M
authors.lastname: Yisireyili
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Shimizu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Saito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Enomoto
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Nishijima
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Niwa
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology*; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007200:Indican / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D020303:Rats, Inbred Dahl
chemical_list: D007200:Indican