Journal
DIABETES OBESITY & METABOLISM
Volume 3, Issue 4, Pages 230-239Publisher
WILEY
DOI: 10.1046/j.1463-1326.2001.00096.x
Keywords
N-phenacylthiazolium bromide (PTB); advanced glycation end products (AGE); diabetic nephropathy; C57BL/6 mice
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Funding
- NIDDK NIH HHS [DK45619] Funding Source: Medline
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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 mug/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 N-epsilon(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.
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