title: Cholestasis induces apoptosis in mice cardiac cells: the possible role of nitric oxide and oxidative stress.
abstract: OBJECTIVE
  Acute cholestasis is associated with cardiovascular complications. The purpose of the present study was to investigate the effect of cholestasis on heart apoptosis and the involvement of nitric oxide (NO) and oxidative stress in the possible altered apoptosis of cholestatic hearts.
  
  
  METHODS
  Cholestasis was induced by bile duct-ligation, and sham-operated mice served as controls. Three days after the surgery, heart tissues were evaluated for apoptosis and the level of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been studied in cardiac tissues. The role of treatment with l-NAME, a non-selective inhibitor of NO synthase, or with d-NAME, an inactive isomer of l-NAME, on cholestatic and sham cardiac apoptosis, level of MDA and CAT, SOD and GSHPx activities was also investigated. The content of NO in cardiac tissue was also determined.
  
  
  RESULTS
  Cholestatic hearts showed structural abnormalities and increased apoptosis compared with sham hearts. Treatment with l-NAME, but not d-NAME, improved both structural abnormalities and enhanced apoptosis of cholestatic hearts. Cholestatic hearts also had an increased level of MDA and decreased activities of CAT and GSHPx, which were not modified by d-NAME treatment. By l-NAME treatment, the level of MDA decreased and activities of CAT, GSHPx and SOD increased in BDL mice. The content of NO was higher in cholestatic cardiac tissue, which was decreased by l-NAME treatment.
  
  
  CONCLUSIONS
  In conclusion, apoptosis in cholestatic heart might have occurred because of NO overproduction, which could induce oxidative stress in the heart of cholestatic mice.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Shafaroodi
authors.forename: Farzad
authors.initials: F
authors.lastname: Ebrahimi
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hashemi
authors.forename: Yousef
authors.initials: Y
authors.lastname: Doostar
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghasemi
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001652:Bile Ducts / Q000601:surgery; D002374:Catalase / Q000378:metabolism; D002779:Cholestasis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006331:Heart Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008026:Ligation; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester