N‐phenacylthiazolium bromide decreases renal and increases urinary advanced glycation end products excretion without ameliorating diabetic nephropathy in C57BL/6 mice

Abstract

In summary, PTB decreased renal AGE accumulation but did not ameliorate glomerular lesions or proteinuria. Thus, cleavage of AGE by PTB is not sufficient to prevent development of diabetic nephropathy in C57BL/6 mice.

The cross-link breaker, N-phenacylthiazolium bromide prevents vascular advanced glycation end-product accumulation

“…Another possibility is that PTB treatment results in the generation of smaller AGEs which can then be more readily excreted in the urine. This concept that cross-link breakers could actually generate proteins which are preferentially excreted by the kidney has been suggested by a preliminary report which explored the effects of PTB in diabetic mice [9]. In that study, PTB treatment was associated with reduced renal AGE accumulation but the appearance of AGEs in the urine which had not been detected previously.…”

The breakdown of pre‐existing advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes

“…Similar findings have been observed with ALT-711 in a series of in vitro experiments to assess the cross-link breaking ability of this agent (unpublished data, Alteon Inc.). Indeed, evidence for this possibility has been obtained in a study in the diabetic mouse where PTB treatment was associated with the appearance of AGEs and AGE fragments in the urine of these animals (50).…”

Diabetes and Advanced Glycoxidation End Products

“…In diabetic rat models, this agent has been shown to decrease AGEs (165,166) but has not decreased nephropathy as measured by proteinuria (166,167). No human studies with this agent are available.…”