Kidney fibrosis is independent of the amount of ascorbic acid in mice with unilateral ureteral obstruction

H. Nishida, T. Kurahashi, Y. Saito, N. Otsuki, M. Kwon, H. Ohtake, M. Yamakawa, K. I. Yamada, S. Miyata, Y. Tomita, J. Fujii

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16 Citations (Scopus)

Abstract

In response to sustained damage to a kidney, fibrosis that can be characterized as the deposition of a collagenous matrix occurs and consequently causes chronic kidney failure. Because most animals used in experiments synthesize ascorbic acid (AsA) from glucose, the roles of AsA in fibrotic kidney diseases are largely unknown. Unilateral ureteric obstruction (UUO) mimics the complex pathophysiology of chronic obstructive nephropathy and is an ideal model for the investigation of the roles of AsA in kidney failure. We examined the impact of a deficiency of Akr1a, a gene that encodes aldehyde reductase and is responsible for the production of AsA, on fibrotic damage caused by UUO in mice. Oxidatively modified DNA was elevated in wild-type and Akr1a-deficient kidneys as a result of UUO to a similar extent, and was only slightly suppressed by the administration of AsA. Even though Akrla-deficient mice could produce only about 10% of the AsA produced by wild-type mice, no difference was observed in collagen I synthesis under pathological conditions. The data implied either a low demand for AsA or the presence of another electron donor for collagen I production in the mouse kidney. Next, we attempted to elucidate the potential causes for oxidative damage in kidney cells during the fibrotic change. We found decreases in mitochondrial proteins, particularly in electron transport complexes, at the initial stage of the kidney fibrosis. The data imply that a dysfunction of the mitochondria leads to an elevation of ROS, which results in kidney fibrosis by stimulating cellular transformation to myofibroblasts.

Original languageEnglish
Pages (from-to)1115-1124
Number of pages10
JournalFree Radical Research
Volume48
Issue number9
DOIs
Publication statusPublished - Sep 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry

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