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Theophylline protects against glycerol-induced acute renal failure: Regulation of heme oxygenase-1 and glutathione in rat kidney

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Abstract

Background

To investigate the mechanism of glycerol-induced renal injury, we examined kidney levels of the cellular antioxidant glutathione and heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, after glycerol injection.

Methods

Male Wistar rats were injected with glycerol to induce acute renal failure. Serum creatinine levels were used as a marker of renal function at 24 hours after glycerol injection. Theophylline and buthionine sulfoximine or vehicle were administered to the rats after glycerol injection, and we determined renal glutathione levels (by biochemical assay) and the levels of HO-1 protein and messenger ribonucleic acid (mRNA; using immunoblot analysis [kidney only]) in various rat organs at 24 hours after glycerol injection.

Results

Glutathione levels abruptly declined after glycerol injection, reached a minimum at 4 hours, then returned to about two thirds of control levels at 24 hours. HO-1 protein was detected at 4 hours and reached a maximum at 24 hours. The induction of HO-1 protein was observed only in the kidney. HO-1 mRNA was faintly expressed at 2 hours, increased until at least 8 hours, and was not detected 24 hours after the treatment. When theophylline was administered to glycerol-injected rats, renal function improved and glutathione levels increased. In addition, the levels of HO-1 protein decreased, compared with those of glycerol-treated rats not given theophylline.

Conclusions

These results suggest that theophylline may act by modulating the HO-1 directly or indirectly.

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Authors and Affiliations

  1. Fourth Department of Internal Medicine, Tokyo Women's Medical College, Tokyo, Japan

    Shino Ishizuka & Masayoshi Sone

  2. Second Division of Pathology, Faculty of Medicine, Yokohama City University, Yokohama, Japan

    Yoji Nagashima

  3. Division of Applied Food Research, National Institute of Health and Nutrition, Tokyo, Japan

    Kiyokazu Hagiwara

  4. Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyodaku, 101, Tokyo, Japan

    Saburo Horikawa

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  1. Shino Ishizuka
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  2. Yoji Nagashima
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  3. Masayoshi Sone
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  4. Kiyokazu Hagiwara
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  5. Saburo Horikawa
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Ishizuka, S., Nagashima, Y., Sone, M. et al. Theophylline protects against glycerol-induced acute renal failure: Regulation of heme oxygenase-1 and glutathione in rat kidney. Clin Exper Neph 1, 204–211 (1997). https://doi.org/10.1007/BF02480696

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  • DOI: https://doi.org/10.1007/BF02480696

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