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

doi:10.1016/S0531-5131(02)01002-6

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

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	169-173
Number of pages	5
Journal	International Congress Series
Volume	1245
Issue number	C
DOIs	https://doi.org/10.1016/S0531-5131(02)01002-6
Publication status	Published - 01 Nov 2002

Keywords

AGE/ALEs
Dyslipidemia
Enalapril
Nephropathy
Pyridoxamine
Retinopathy
Vitamin E

ASJC Scopus subject areas

Medicine(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0531-5131(02)01002-6

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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

Thorpe, Suzanne R. ; Alderson, Nathan L. ; Chachich, Mark E. ; Januszweski, Andrzej ; Youssef, Nancy N. ; Jimenez, Stephanie M. ; Gardiner, Tom ; Frizzell, Norma ; Canning, Paul ; Lichanska, Agnieszka ; Baynes, John W. ; Stitt, Alan W. / Role of dyslipidemia and AGE/ALE formation in the progression of nephropathy and retinopathy in STZ-diabetic rats. In: International Congress Series. 2002 ; Vol. 1245, No. C. pp. 169-173.

@article{dc4d497cac7e41c38b2a521f4638c7cd,

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

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.",

keywords = "AGE/ALEs, Dyslipidemia, Enalapril, Nephropathy, Pyridoxamine, Retinopathy, Vitamin E",

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

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doi = "10.1016/S0531-5131(02)01002-6",

language = "English",

volume = "1245",

pages = "169--173",

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Thorpe, SR, Alderson, NL, Chachich, ME, Januszweski, A, Youssef, NN, Jimenez, SM, Gardiner, T, Frizzell, N, Canning, P, Lichanska, A, Baynes, JW & Stitt, AW 2002, 'Role of dyslipidemia and AGE/ALE formation in the progression of nephropathy and retinopathy in STZ-diabetic rats', International Congress Series, vol. 1245, no. C, pp. 169-173. https://doi.org/10.1016/S0531-5131(02)01002-6

Role of dyslipidemia and AGE/ALE formation in the progression of nephropathy and retinopathy in STZ-diabetic rats. / Thorpe, Suzanne R.; Alderson, Nathan L.; Chachich, Mark E.; Januszweski, Andrzej; Youssef, Nancy N.; Jimenez, Stephanie M.; Gardiner, Tom; Frizzell, Norma; Canning, Paul; Lichanska, Agnieszka; Baynes, John W.; Stitt, Alan W.

In: International Congress Series, Vol. 1245, No. C, 01.11.2002, p. 169-173.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Role of dyslipidemia and AGE/ALE formation in the progression of nephropathy and retinopathy in STZ-diabetic rats

AU - Thorpe, Suzanne R.

AU - Alderson, Nathan L.

AU - Chachich, Mark E.

AU - Januszweski, Andrzej

AU - Youssef, Nancy N.

AU - Jimenez, Stephanie M.

AU - Gardiner, Tom

AU - Frizzell, Norma

AU - Canning, Paul

AU - Lichanska, Agnieszka

AU - Baynes, John W.

AU - Stitt, Alan W.

PY - 2002/11/1

Y1 - 2002/11/1

N2 - 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.

AB - 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.

KW - AGE/ALEs

KW - Dyslipidemia

KW - Enalapril

KW - Nephropathy

KW - Pyridoxamine

KW - Retinopathy

KW - Vitamin E

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U2 - 10.1016/S0531-5131(02)01002-6

DO - 10.1016/S0531-5131(02)01002-6

M3 - Article

AN - SCOPUS:4544350960

VL - 1245

SP - 169

EP - 173

JO - International congress series / Excerpta Medica

JF - International congress series / Excerpta Medica

SN - 0531-5131

IS - C

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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