α-Lipoic acid protects diabetic apolipoprotein E-deficient mice from nephropathy

Xianwen Yi, Volker Nickeleit, Leighton R James, Nobuyo Maeda

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Aim: Both hyperglycemia and hyperlipidemia increase oxidative stress and contribute to the development of diabetic nephropathy (DN). We investigated the effects of α-lipoic acid, a natural antioxidant and a cofactor in the multienzyme complexes, on the development of DN in diabetic apolipoprotein E-deficient mice. Methods: Twelve-week-old male apoE-/- mice on C57BL/6J genetic background were made diabetic with injections of streptozotocin (STZ). STZ-treated diabetic apoE-/- mice and non-diabetic control were fed with a synthetic high-fat (HF) diet with or without lipoic acid (LA) supplementation. Multiple parameters including plasma glucose, cholesterol, oxidative stress markers, cytokines, and kidney cortex gene expression, and glomerular morphology were evaluated. Results: LA supplementation markedly protected the β cells, reduced cholesterol levels, and attenuated albuminuria and glomerular mesangial expansion in the diabetic mice. Renoprotection by LA was equally effective regardless of whether the dietary supplementation was started 4 weeks before, simultaneously with, or 4 weeks after the induction of diabetes by STZ. LA supplementation significantly improved DN and oxidative stress in the diabetic mice. Severity of albuminuria was positively correlated with level of thiobarbituric acid reactive substances (TBARs) in the kidney (r 2=0.62, P<.05). Diabetes significantly changed the kidney expression of Rage, Sod2, Tgfb1 and Ctgf, Pdp2, nephrin, and Lias. LA supplementation corrected these changes except that it further suppressed the expression of the Lias gene coding for lipoic acid synthase. Conclusions: Our data indicate that LA supplementation effectively attenuates the development and progression of DN through its antioxidant effect as well as enhances glucose oxidation.

Original languageEnglish (US)
Pages (from-to)193-201
Number of pages9
JournalJournal of Diabetes and its Complications
Volume25
Issue number3
DOIs
StatePublished - May 1 2011
Externally publishedYes

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Thioctic Acid
Apolipoproteins E
Diabetic Nephropathies
Oxidative Stress
Albuminuria
Streptozocin
Antioxidants
Cholesterol
Multienzyme Complexes
Rage
Kidney
Gene Expression
Glucose
Kidney Cortex
Experimental Diabetes Mellitus
Thiobarbituric Acid Reactive Substances
High Fat Diet
Dietary Supplements
Hyperlipidemias
Inbred C57BL Mouse

Keywords

  • Antioxidants
  • Apolipoprotein e null mice
  • Diabetes
  • Diabetic nephropathy
  • Lipoic acid
  • Oxidative stress
  • Streptozotocin

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

α-Lipoic acid protects diabetic apolipoprotein E-deficient mice from nephropathy. / Yi, Xianwen; Nickeleit, Volker; James, Leighton R; Maeda, Nobuyo.

In: Journal of Diabetes and its Complications, Vol. 25, No. 3, 01.05.2011, p. 193-201.

Research output: Contribution to journalArticle

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abstract = "Aim: Both hyperglycemia and hyperlipidemia increase oxidative stress and contribute to the development of diabetic nephropathy (DN). We investigated the effects of α-lipoic acid, a natural antioxidant and a cofactor in the multienzyme complexes, on the development of DN in diabetic apolipoprotein E-deficient mice. Methods: Twelve-week-old male apoE-/- mice on C57BL/6J genetic background were made diabetic with injections of streptozotocin (STZ). STZ-treated diabetic apoE-/- mice and non-diabetic control were fed with a synthetic high-fat (HF) diet with or without lipoic acid (LA) supplementation. Multiple parameters including plasma glucose, cholesterol, oxidative stress markers, cytokines, and kidney cortex gene expression, and glomerular morphology were evaluated. Results: LA supplementation markedly protected the β cells, reduced cholesterol levels, and attenuated albuminuria and glomerular mesangial expansion in the diabetic mice. Renoprotection by LA was equally effective regardless of whether the dietary supplementation was started 4 weeks before, simultaneously with, or 4 weeks after the induction of diabetes by STZ. LA supplementation significantly improved DN and oxidative stress in the diabetic mice. Severity of albuminuria was positively correlated with level of thiobarbituric acid reactive substances (TBARs) in the kidney (r 2=0.62, P<.05). Diabetes significantly changed the kidney expression of Rage, Sod2, Tgfb1 and Ctgf, Pdp2, nephrin, and Lias. LA supplementation corrected these changes except that it further suppressed the expression of the Lias gene coding for lipoic acid synthase. Conclusions: Our data indicate that LA supplementation effectively attenuates the development and progression of DN through its antioxidant effect as well as enhances glucose oxidation.",
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N2 - Aim: Both hyperglycemia and hyperlipidemia increase oxidative stress and contribute to the development of diabetic nephropathy (DN). We investigated the effects of α-lipoic acid, a natural antioxidant and a cofactor in the multienzyme complexes, on the development of DN in diabetic apolipoprotein E-deficient mice. Methods: Twelve-week-old male apoE-/- mice on C57BL/6J genetic background were made diabetic with injections of streptozotocin (STZ). STZ-treated diabetic apoE-/- mice and non-diabetic control were fed with a synthetic high-fat (HF) diet with or without lipoic acid (LA) supplementation. Multiple parameters including plasma glucose, cholesterol, oxidative stress markers, cytokines, and kidney cortex gene expression, and glomerular morphology were evaluated. Results: LA supplementation markedly protected the β cells, reduced cholesterol levels, and attenuated albuminuria and glomerular mesangial expansion in the diabetic mice. Renoprotection by LA was equally effective regardless of whether the dietary supplementation was started 4 weeks before, simultaneously with, or 4 weeks after the induction of diabetes by STZ. LA supplementation significantly improved DN and oxidative stress in the diabetic mice. Severity of albuminuria was positively correlated with level of thiobarbituric acid reactive substances (TBARs) in the kidney (r 2=0.62, P<.05). Diabetes significantly changed the kidney expression of Rage, Sod2, Tgfb1 and Ctgf, Pdp2, nephrin, and Lias. LA supplementation corrected these changes except that it further suppressed the expression of the Lias gene coding for lipoic acid synthase. Conclusions: Our data indicate that LA supplementation effectively attenuates the development and progression of DN through its antioxidant effect as well as enhances glucose oxidation.

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