Me. Cooper et al., The cross-link breaker, N-phenacylthiazolium bromide prevents vascular advanced glycation end-product accumulation, DIABETOLOG, 43(5), 2000, pp. 660-664
Aims/hypothesis. Advanced glycation is postulated to have a pivotal role in
mediating diabetic vascular complications. The emergence of thiazolium com
pounds such as N-phenacylthiazolium bromide which cleave preformed advanced
glycation end products (AGEs) has allowed us to explore the effects of the
se agents on the vascular AGE accumulation and hypertrophy associated with
diabetes.
Methods. Control and streptozotocin diabetic rats were selected at random f
or no treatment or treatment with. N-phenacylthiazolium bromide (10 mg/kg i
ntraperitoneally) and followed for 3 weeks. In a separate study, interventi
on with N-phenacylthiazolium bromide was delayed until after 3 weeks of dia
betes and then given for 3 weeks (total of 6 weeks).
Results. Diabetes was associated with increased mesenteric vascular advance
d glycation end products, as assessed by radioimmunoassay and immunohistoch
emistry. This increase in vascular AGE accumulation was prevented by N-phen
acylthiazolium bromide treatment. Diabetes-associated mesenteric vascular h
ypertrophy was attenuated by treatment with N-phenacylthiazolium bromide on
ly if given from the time of induction of diabetes.
Conclusion/interpretation. Cross-link breakers seem to be effective in prev
enting or reversing accumulation of advanced glycation end-products in bloo
d vessels and have the potential to play a part in the treatment of diabeti
c vascular complications.