Abstract
The present study was conducted to elucidate the role of oxidative stress and nuclear factor-kappaB (NF-kappaB) in the beneficial effects of angiotensin receptor blockade on obstructive nephropathy. Unilateral ureteral occlusion in rats elicited tubulo-interstitial fibrosis with concomitant macrophage infiltration and increased expression of monocyte chemoattractant protein-1. These changes were accompanied by an induction of renal cortical lipid peroxidation and activation of NF-kappaB. Both an AT(1) antagonist, candesartan, and a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated these changes and to a similar extent. These results suggest that the beneficial effects of angiotensin blockade are mediated by the inhibition of oxidative stress and subsequent NF-kappaB activation in obstructive nephropathy.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin Receptor Antagonists
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Animals
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Antioxidants / pharmacology
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Benzimidazoles / pharmacology
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Biphenyl Compounds
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Fibrosis
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Kidney / metabolism*
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Kidney / pathology
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Kidney / physiopathology*
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Male
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Oxidative Stress
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Pyrrolidines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species / metabolism
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Renin-Angiotensin System*
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Tetrazoles / pharmacology
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Thiocarbamates / pharmacology
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Ureteral Obstruction / metabolism
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Ureteral Obstruction / pathology
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Ureteral Obstruction / physiopathology*
Substances
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Angiotensin Receptor Antagonists
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Antioxidants
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Benzimidazoles
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Biphenyl Compounds
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NF-kappa B
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Pyrrolidines
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Reactive Oxygen Species
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Tetrazoles
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Thiocarbamates
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pyrrolidine dithiocarbamic acid
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candesartan