Premium
Allopurinol Attenuates Left Ventricular Dysfunction In The Early Stage of Streptozotocin‐Induced Diabetes In Rats
Author(s) -
Xu Yuan,
Gao Xia,
Xu Bo,
Liu Huimin,
Liu Yanan,
Irwin Michael G,
Xia Zhengyuan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb374
Subject(s) - diabetic cardiomyopathy , medicine , streptozotocin , endocrinology , xanthine oxidase , diabetes mellitus , ventricle , oxidative stress , allopurinol , ejection fraction , xanthine oxidase inhibitor , diastole , xanthine , cardiomyopathy , heart failure , chemistry , blood pressure , biochemistry , enzyme
Xanthine oxidase‐derived superoxide production and oxidative stress plays an important role in the development of diabetic complications (Diabetes 2002;51(4):1118–24) including diabetic cardiomyopathy. We hypothesized that treatment with the xanthine oxidase inhibitor allopurinol (ALP) may attenuate or prevent the development of left ventricle (LV) diastolic dysfunction, an early sign of diabetic cardiomyopathy (Cardiology 2002;98:33–9), in rats with streptozotocin (STZ)‐induced diabetes. Control Sprague‐Dawley (C) or STZ‐induced diabetic (D) rats (220±20g) were either untreated or treated with ALP (100 mg/kg/day) for four weeks starting at one week after STZ injection. In D rats, both plasma and cardiac tissue levels of 15‐F2t‐isoprostane, a specific index of oxidative damage, were increased (P<0.05 vs. C) at the 5th week, accompanied with significant increase in left ventricle (LV) weight/body weight ratio and decreases in LV end‐diastolic volume and stroke volume (all P<0.05 D vs. C). All these changes were either significantly attenuated or prevented by treatment with ALP. In addition, LV ejection fraction in D rats treated with ALP was higher than that in untreated D rats (P<0.05). It is concluded that ALP can attenuate hyperglycemia‐induced oxidative stress and subsequently present left ventricular dysfunction in early diabetes.