title: The role of spironolactone on myocardial oxidative stress in rat model of streptozotocin-induced diabetes.
abstract: BACKGROUND
  Diabetes mellitus (DM) is linked to cardiovascular diseases development and progression. Aldosterone contributes to cardiac oxidative stress and remodeling.
  
  
  OBJECTIVE
  To evaluate the impact of spironolactone (an aldosterone antagonist) on markers of myocardial redox status in a rat model of streptozotocin (STZ)-induced DM.
  
  
  METHODS
  Adult Sprague Dawley rats were randomized into four groups; controls, spironolactone-treated rats (Spir), diabetic rats (DM), and diabetic rats treated with spironolactone (DM+Spir) for 4 weeks. Blood pressure and cardiac levels of aldosterone and oxidants/antioxidants were measured.
  
  
  RESULTS
  STZ-induced DM but did not cause hypertension or dyslipidemia in either spironolactone-treated or spironolactone-untreated rats. Aldosterone and aldosterone synthase levels were increased in both the DM and DM+Spir groups compared to control. In parallel, total nitrite and nitrotyrosine levels were increased and vitamin E antioxidant levels were reduced in the DM group. Spironolactone use reduced cardiac total nitrite levels and improved vitamin E levels. Glutathione reductase/peroxidase activities were increased in the DM and DM+Spir groups without changes in the ratio of reduced to oxidized form of glutathione. Superoxide dismutase (SOD) and catalase activities were increased in the DM group. Lipid peroxidation products were similar among the groups.
  
  
  CONCLUSIONS
  The increase in total nitrite/nitrotyrosine in DM promoted significant compensatory increases in antioxidant activities of SOD, catalase and glutathione peroxidase/reductase probably to prevent cardiac oxidative damage. The use of spironolactone reduced nitrite generation and improved vitamin E levels independent of blood pressure.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Fadia
authors.initials: F
authors.lastname: Mayyas
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Karem H
authors.initials: KH
authors.lastname: Alzoubi
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Ruwidah
authors.initials: R
authors.lastname: Bonyan
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000494:pharmacology*; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D009573:Nitrites; D014810:Vitamin E; D013148:Spironolactone; C002744:3-nitrotyrosine; D014443:Tyrosine; D000450:Aldosterone; D013311:Streptozocin; D002374:Catalase; D005979:Glutathione Peroxidase; D019405:Cytochrome P-450 CYP11B2; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione
keywords: Aldosterone; Diabetes mellitus; Oxidative stress; Spironolactone; Streptozotocin