The cross-link breaker, N-phenacylthiazolium bromide prevents vascular advanced glycation end-product accumulation.
OBJECTIVE
Advanced glycation is postulated to have a pivotal role in mediating diabetic vascular complications. The emergence of thiazolium compounds such as N-phenacylthiazolium bromide which cleave preformed advanced glycation end products (AGEs) has allowed us to explore the effects of these agents on the vascular AGE accumulation and hypertrophy associated with diabetes.


METHODS
Control and streptozotocin diabetic rats were selected at random for no treatment or treatment with N-phenacylthiazolium bromide (10 mg/kg intraperitoneally) and followed for 3 weeks. In a separate study, intervention with N-phenacylthiazolium bromide was delayed until after 3 weeks of diabetes and then given for 3 weeks (total of 6 weeks).


RESULTS
Diabetes was associated with increased mesenteric vascular advanced glycation end products, as assessed by radioimmunoassay and immunohistochemistry. This increase in vascular AGE accumulation was prevented by N-phenacylthiazolium bromide treatment. Diabetes-associated mesenteric vascular hypertrophy was attenuated by treatment with N-phenacylthiazolium bromide only if given from the time of induction of diabetes.


CONCLUSIONS
Cross-link breakers seem to be effective in preventing or reversing accumulation of advanced glycation end-products in blood vessels and have the potential to play a part in the treatment of diabetic vascular complications.
Cooper
M E
ME
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, West Heidelberg, Australia.
Thallas
V
V
Forbes
J
J
Scalbert
E
E
Sastra
S
S
Darby
I
I
Soulis
T
T
D000818:Animals; D001794:Blood Pressure; D001808:Blood Vessels / Q000737:chemistry / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*
D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D013844:Thiazoles; C101705:N-phenacylthiazolium bromide