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

Abstract

AIMS:

Advanced glycation end products (AGE), which form from the non-enzymatic reaction of proteins and sugars, have been implicated in the pathogenesis of diabetic nephropathy. Recently, a compound [N-phenacylthiazolium bromide (PTB)] has been described which cleaves alpha,beta-dicarbonyl compounds. In the present study we used diabetic C57BL/6 mice to determine if PTB altered renal AGE levels and reduced diabetic glomerulosclerosis.

METHODS:

Mice with stable hyperglycaemia induced by streptozotocin were given daily subcutaneous injections of either PTB (10 microg/g) or saline for 12 weeks. Renal-collagen bound AGE and urinary AGE-peptides were measured by ELISA using an anti-AGE-RNase antibody. Renal collagen-released Nepsilon(carboxymethyl)lysine (CML) and pentosidine were determined by high pressure liquid chromatography (HPLC). Glomerular lesions (volume and mesangial/total surface area) were evaluated by computer-assisted image analysis. We determined urinary protein/creatinine ratio as a functional parameter. AGE localization was examined by immunohistochemistry using the anti-AGE-RNase antibody.

RESULTS:

Renal collagen-bound AGE were decreased and urinary AGE excretion was increased in PTB-treated diabetic mice. However, collagen-released CML and pentosidine were similar in both groups. Glomerular histology and morphometric analysis revealed also no differences between PTB-and saline-treated diabetic mice. The urinary protein/creatinine ratio was unaffected by PTB-treatment. AGE staining by anti-AGE-RNase antibody was present in Bowman's capsules, glomerular basement membranes and cortical tubules. It was decreased in all structures in PTB-treated diabetic mice.

CONCLUSION:

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.

• Authors: S B Schwedler, P Verbeke, H Bakala, M F Weiss, J Vilar, P Depreux, E Fourmaintraux, L J Striker, G E Striker
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 3 Issue 4 Pg. 230-9 (Aug 2001) ISSN: 1462-8902 [Print] England
• PMID: 11520302 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycation End Products, Advanced
• N-phenacylthiazolium bromide
• Thiazoles
• Collagen
• Arginine
• pentosidine
• Lysine

Topics

• Animals
• Arginine (analogs & derivatives, pharmacology)
• Collagen (metabolism)
• Diabetes Mellitus, Experimental (physiopathology, urine)
• Diabetic Nephropathies (pathology, physiopathology, urine)
• Female
• Glomerular Mesangium (drug effects, pathology)
• Glycation End Products, Advanced (metabolism, urine)
• Kidney (drug effects, pathology, physiopathology)
• Kidney Glomerulus (drug effects, pathology)
• Lysine (analogs & derivatives, pharmacology)
• Mice
• Mice, Inbred C57BL
• Proteinuria
• Thiazoles (pharmacology)