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Lipoic acid supplementation prevents angiotensin II-induced renal injury

Item Type:Article
Title:Lipoic acid supplementation prevents angiotensin II-induced renal injury
Creators Name:Mervaala, E. and Finckenberg, P. and Lapatto, R. and Mueller, D.N. and Park, J.K. and Dechend, R. and Ganten, D. and Vapaatalo, H. and Luft, F.C.
Abstract:BACKGROUND: Angiotensin II (Ang II)-induced renal injury is associated with perivascular inflammation, cell proliferation, and increased superoxide production in the vascular wall. We tested whether lipoic acid, an endogenous antioxidant, protects against the Ang II-induced inflammatory response and end-organ damage.METHODS:Light microscopy, immunohistochemistry, electrophoretic mobility shift assay, Northern blots, and high-pressure liquid chromatography (HPLC) were used in kidneys from double transgenic rats (dTGR) harboring human renin and angiotensinogen genes and normotensive Sprague Dawley (SD) rats. The effects of lipoic acid supplementation for three weeks were examined in dTGR and SD rats. RESULTS:Lipoic acid effectively prevented Ang II-induced glomerular and vascular damage in the kidneys and completely prevented the development of albuminuria. Ang II-induced leukocyte infiltration and cell proliferation in the kidney were attenuated. The redox-sensitive transcription factors nuclear factor (kappa) B (NF-kappa B) and activator protein-1 (AP-1) in the kidneys were increased in dTGR compared with SD, and were effectively reduced. Renal glutathione levels were much higher in dTGR than in SD, while the opposite was true for cysteine levels. These results suggested increased renal glutathione oxidation in dTGR, leading to cysteine shortage. Lipoic acid partly prevented renal cysteine depletion and increased hepatic cysteine and glutathione concentrations. This effect was accompanied by increased hepatic gamma-glutamylcysteine synthetase mRNA expression. CONCLUSION: Our in vivo results suggest that lipoic acid protects against Ang II-induced renal injury through anti-inflammatory/antioxidative mechanisms. The effects are associated with decreased NF-kappa B and AP-1 activation, as well as improved thiol homeostasis.
Keywords:Albuminuria, Angiotensin II, Antioxidants, Blood Pressure, Cardiomegaly, Cell Division, Glutathione, Homeostasis, Kidney, Leukocytes, Myocardium, NF-kappa B, Nephritis, Oxidative Stress, Thioctic Acid, Transcription Factor AP-1, Vasoconstrictor Agents, Animals, Rats, Sprague-Dawley Rats
Source:Kidney International
Publisher:Nature Publishing Group
Page Range:501-508
Date:August 2003
Official Publication:https://doi.org/10.1046/j.1523-1755.2003.00108.x
PubMed:View item in PubMed

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