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Hyperbaric oxygen treatment augments the efficacy of cilazapril and simvastatin regimens in an experimental nephrotic syndrome model

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Abstract

Background

Oxidative stress plays a role in the mechanism of chronic kidney disease (CKD), and antioxidant regimes are regarded as promising treatment modalities. We compared the effects of cilazapril, simvastatin, and hyperbaric oxygen (HBO) treatment on proteinuria and on oxidative stress in adriamycine (ADR)-induced proteinuria.

Methods

Seventy male Sprague–Dawley rats were housed, and 60 were injected with ADR to induce nephrosis. After the stabilization of proteinuria, rats were treated for 6 weeks with simvastatin (n = 10, 4 mg/kg/day), cilazapril (n = 10, 10 mg/kg/day), HBO (n = 10, 2.8 athmosphere absolute, 90 min/daily), HBO + cilazapril (n = 10), HBO + simvastatin (n = 10), and vehicle (n = 10). After euthanization at 12 weeks, protein carbonyl (PCO), superoxide dismutase (SOD), and glutathion peroxidase (GPx) levels were analyzed from tissues. The histological alterations in the kidneys were determined by semiquantitative scoring.

Results

Protein carbonyl (PCO) levels were higher (p < 0.001), and the GPx and SOD levels were lower (p < 0.001 for all) in the nephrotic rats. Proteinuria was correlated to PCO (r = 0.483), GPx (r = −0.686), or SOD (r = −0.620) (p < 0.001 for all). Superoxide dismutase (SOD) (beta = −0.381, p = 0.02) and GPx (beta = −0.509, p < 0.001) were independently related to proteinuria levels. Both cilazapril and simvastatin significantly improved GPx, SOD, PCO, and proteinuria. When HBO was combined with either drug, the above markers further improved (p < 0.001). Both regimens caused distinct histological features, while the combination of HBO made much significant histological improvement.

Conclusion

Both cilazapril and simvastatin regimens improve oxidative stress and proteinuria, while the effects significantly increase with the combination of HBO treatment. HBO seems to be a candidate antioxidant strategy in glomerular diseases.

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Acknowledgments

The Research Center of GATA supported this study. We thank MERCK and ROCHE Research Laboratories for providing simvastatin and cilazapril. Mahmut Ilker Yilmaz benefited from EDTA-ERA Fellowships.

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Authors and Affiliations

  1. Department of Internal Medicine, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey

    Alper Sonmez

  2. Department of Nephrology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey

    Mahmut Ilker Yilmaz, Kayser Caglar, Tayfun Eyileten, Mujdat Yenicesu, Yusuf Oguz & Abdulgaffar Vural

  3. Department of Physiology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey

    Ahmet Korkmaz & Turgut Topal

  4. Department of Pathology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey

    Ayper Kaya

  5. Department of Urology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey

    Seref Basal

  6. Department of Biochemistry, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey

    Osman Metin Ipcioglu

  7. Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, K 56 Karolinska University Hospital at Huddinge, 141 86, Huddinge, Stockholm, Sweden

    Mahmut Ilker Yilmaz

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  1. Alper Sonmez
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Corresponding author

Correspondence to Mahmut Ilker Yilmaz.

Additional information

Alper Sonmez and Mahmut Ilker Yilmaz contributed equally to this article.

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Sonmez, A., Yilmaz, M.I., Korkmaz, A. et al. Hyperbaric oxygen treatment augments the efficacy of cilazapril and simvastatin regimens in an experimental nephrotic syndrome model. Clin Exp Nephrol 12, 110–118 (2008). https://doi.org/10.1007/s10157-007-0017-2

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  • DOI: https://doi.org/10.1007/s10157-007-0017-2

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