title: Allopurinol attenuates left ventricular dysfunction in rats with early stages of streptozotocin-induced diabetes.
abstract: BACKGROUND
  Xanthine oxidase-derived superoxide production and oxidative stress contribute to the development of diabetic complications including diabetic cardiomyopathy. We hypothesized that xanthine oxidase-inhibitor allopurinol (ALP) may decrease hyperglycemia-induced oxidative stress, ameliorate cardiomyocyte hypertrophy and fibrosis, and attenuate the development of left ventricle (LV) diastolic dysfunction in rats with streptozotocin (STZ)-induced diabetes.
  
  
  METHODS
  Control Sprague Dawley (C) or streptozotocin-induced diabetic (D) rats were either untreated or treated with allopurinol (100 mg/kg/day) for 4 weeks starting at 1 week after streptozotocin injection. Free 15-F2t-isoprostane, a specific indicator of oxidative stress was measured by enzymatic immunoassay. The cardiomyocyte cross-sectional area was assessed by hematoxylin and eosin-stained paraffin-embedded sections of LVs. Myocardial collagens I and III were assessed by immunol histochemistry and Western blotting. Echocardiography was performed to characterize cardiac structure and function.
  
  
  RESULTS
  In diabetic rats, both plasma and cardiac tissue levels of free 15-F2t-isoprostane were increased (p < 0.05 vs. control), accompanied with significant increase (p < 0.05 vs. control) in cross-section area and myocardial collagen deposition of LV cardiomyocyte. Echocardiography in diabetic rats showed that LV weight/body weight ratio was significantly higher than in control rats, whereas the levels of LV end-diastolic volume and stroke volume were decreased (all p < 0.05 diabetic vs. control). All these changes were either attenuated or prevented by allopurinol. In addition, LV ejection fraction in diabetic rats treated with allopurinol was higher than that in untreated diabetic rats (p < 0.05).
  
  
  CONCLUSIONS
  Allopurinol can attenuate hyperglycemia-induced oxidative stress, ameliorate cardiomyocyte hypertrophy and fibrosis and subsequently prevent left ventricular dysfunction in early diabetes.
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.forename: Hui-min
authors.initials: HM
authors.lastname: Liu
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Lei
authors.forename: Yin-qin
authors.initials: YQ
authors.lastname: Zhong
authors.forename: Michael G
authors.initials: MG
authors.lastname: Irwin
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use*; D015153:Blotting, Western; D024042:Collagen Type I / Q000378:metabolism; D048909:Diabetes Complications / Q000209:etiology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000517:prevention & control*; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000517:prevention & control*; D015237:Dinoprost / Q000031:analogs & derivatives; D004452:Echocardiography; D007124:Immunoenzyme Techniques; D028421:Isoprostanes / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000963:Antimetabolites; D024042:Collagen Type I; D028421:Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D000493:Allopurinol; D015237:Dinoprost