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Serofendic acid protects from iodinated contrast medium and high glucose probably against superoxide production in LLC-PK1 cells

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Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

It is well known that patients with chronic kidney disease, including diabetic nephropathy, often develop cardiovascular diseases. In case of radiographic procedures, reduced renal function may be deteriorated by the use of iodinated contrast medium (CM). This is known as CM-induced nephropathy. In this study, we have focused on the mechanisms of this type of injury in diabetic nephropathy and the preventive effects of serofendic acid.

Methods

We evaluated the cytotoxicity of CM and high glucose on tubular epithelial cells using an LLC-PK1 cell line, and measured cell viability with an alamarBlue assay. We further evaluated superoxide production levels measured by dihydroethidium. We also examined the protective effects of serofendic acid on cytotoxicity with superoxide production of CM and high glucose.

Results

CM reduced cell numbers in a dose-dependent and time-dependent manner in LLC-PK1 cells. Furthermore, cytotoxicity of CM in diluted concentration was additively influenced by high glucose. CM and high glucose increased superoxide production, which was evaluated by the response to dihydroethidium, and was suppressed by serofendic acid. Cytotoxicity of CM, high glucose, and H2O2 was suppressed by serofendic acid, as well as the suppression by N-acetylcysteine on CM toxicity. Interestingly, the recovery by serofendic acid in H2O2- and high glucose-induced cellular injury was to the basal level, in contrast with the partial recovery from CM-induced injury. Finally, serofendic acid suppressed CM-induced injury and high glucose-induced apoptosis.

Conclusions

These results suggest that CM and high glucose induce cytotoxicity and oxidative stress in LLC-PK1 cells and that serofendic acid protects the injury probably from superoxide generation.

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Authors and Affiliations

  1. Division of Molecular Medicine, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan

    Osamu Kitamura, Kazuhide Uemura, Hisayo Kitamura & Takahiko Ono

  2. Department of Neuroscience for Drug Discovery, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, Japan

    Hachiro Sugimoto

  3. Department of Pharmacology, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, Japan

    Akinori Akaike

Authors
  1. Osamu Kitamura
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  2. Kazuhide Uemura
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  3. Hisayo Kitamura
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  4. Hachiro Sugimoto
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  5. Akinori Akaike
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  6. Takahiko Ono
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Correspondence to Takahiko Ono.

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Kitamura, O., Uemura, K., Kitamura, H. et al. Serofendic acid protects from iodinated contrast medium and high glucose probably against superoxide production in LLC-PK1 cells. Clin Exp Nephrol 13, 15–24 (2009). https://doi.org/10.1007/s10157-008-0081-2

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  • DOI: https://doi.org/10.1007/s10157-008-0081-2

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