Role of dyslipidemia and AGE/ALE formation in the progression of nephropathy and retinopathy in STZ-diabetic rats

Suzanne R. Thorpe*, Nathan L. Alderson, Mark E. Chachich, Andrzej Januszweski, Nancy N. Youssef, Stephanie M. Jimenez, Tom Gardiner, Norma Frizzell, Paul Canning, Agnieszka Lichanska, John W. Baynes, Alan W. Stitt

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We hypothesized that the beneficial effects of a variety of pharmacological agents on the progression of diabetic complications were mediated by a common pathway limiting the formation of advanced glycation and advanced lipoxidation end products (AGEs/ALEs) on protein. We studied the effects of the AGE/ALE inhibitor pyridoxamine (PM), the antioxidant vitamin E (VE) and the ACE inhibitor enalapril (EP) on the development of nephropathy and retinopathy in STZ-induced diabetic rats over 29 weeks. Blood glucose and glycohemoglobin were similar in all diabetic groups. Plasma lipids rose continuously in diabetic animals and only PM significantly attenuated this increase. Early nephropathy was indicated by increased plasma creatinine, and urinary albumin, protein and TGF-β excretion in untreated rats. While all interventions limited renal damage to some extent, PM was the most effective, although the increased expression of renal laminin β1 and fibronectin mRNA was normalized by all therapies. Measurement of retinal damage (acellular capillaries, vascular basement membrane-associated laminin) showed that only PM significantly limited signs of early retinopathy in diabetic rats. Only PM limited the increases in the AGE/ALEs in renal and retinal tissue, and in skin collagen, of diabetic rats. Our results suggest that limiting both dyslipidemia and AGE/ALE formation is required for maximum protection of renal and retinal function in the STZ-diabetic rat.

Original languageEnglish
Pages (from-to)169-173
Number of pages5
JournalInternational Congress Series
Volume1245
Issue numberC
DOIs
Publication statusPublished - 01 Nov 2002

Keywords

  • AGE/ALEs
  • Dyslipidemia
  • Enalapril
  • Nephropathy
  • Pyridoxamine
  • Retinopathy
  • Vitamin E

ASJC Scopus subject areas

  • Medicine(all)

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    Thorpe, S. R., Alderson, N. L., Chachich, M. E., Januszweski, A., Youssef, N. N., Jimenez, S. M., Gardiner, T., Frizzell, N., Canning, P., Lichanska, A., Baynes, J. W., & Stitt, A. W. (2002). Role of dyslipidemia and AGE/ALE formation in the progression of nephropathy and retinopathy in STZ-diabetic rats. International Congress Series, 1245(C), 169-173. https://doi.org/10.1016/S0531-5131(02)01002-6