Open AccessC16, a novel advanced glycation endproduct breaker, restores cardiovascular dysfunction in experimental diabetic rats 1
Author(s) -
CHENG Gang,
WANG Lili,
QU Wensheng,
LONG Long,
CUI Hao,
LIU Hongying,
CAO Yinglin,
LI Song
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00240.x
Subject(s) - diabetes mellitus , medicine , glycation , streptozotocin , hemodynamics , ventricle , pathogenesis , aorta , endocrinology , cardiology
Aim: Advanced glycation endproducts (AGE) have been implicated in the pathogenesis of diabetic complications, including diabetic cardiovascular dysfunction. 3‐[2‐(4‐Bromo‐phenyl)‐1‐methyl‐2‐oxo‐ethyl]‐4,5,6,7‐tetrahydro‐benzothiazol‐3‐ium bromide (C16), a novel AGE breaker, was investigated for its effects on the development of cardiovascular disease in diabetic rats. Methods: Rats that had streptozotocin‐induced diabetes for 12 weeks were divided into groups receiving C16 or vehicle by gavage. Results: In hemodynamic studies of the left ventricle, C16 treatment (25 or 50 mg/kg) for 4 weeks resulted in a significant increase in left ventricular systolic pressure, +d p /d t max , and ‐d p /d t max as compared with vehicletreated diabetic rats. Furthermore, in hemodynamic studies of the cardiovascular system, C16 (12.5, 25, or 50 mg/kg) treatment for 4 weeks resulted in a dosedependent and significant increase in cardiac output, a reduction of total peripheral resistance, and an increase in systemic arterial compliance when compared with vehicle‐treated diabetic rats. Biochemical studies showed that C16 treatment also resulted in a significant decrease in immunoglobulin G‐red blood cell surface crosslink content and an increase in collagen solubility. Morphological and immunohistochemical examinations indicated that C16 was able to prevent increases of the collagen type III/I ratio in the aorta and decrease the accumulation of AGE in the aorta. Conclusion: C16 has the ability to reduce AGE accumulation in tissues in vivo , and can restore diabetes‐associated cardiovascular disorders in rats. This provides a potential therapeutic approach for cardiovascular disease associated with diabetes and aging in humans.