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MnTMPyP, a superoxide dismutase/catalase mimetic, decreases inflammatory indices in ischemic acute kidney injury

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Abstract

Objective

This study investigates the effect of a superoxide dismutase mimetic, MnTMPyP, on pro- and anti-inflammatory cytokines in acute renal ischemia–reperfusion (IR).

Materials and treatment

Male Sprague–Dawley rats underwent bilateral clamping of the renal arteries for 45 min followed by 1, 4, or 24 h of reperfusion. A subset of animals was treated with MnTMPyP (5 mg/kg, i.p.) or saline. Porcine proximal tubular epithelial cells were ATP-depleted for 4 h followed by recovery for 2 h.

Methods

Cytokines were analyzed by ELISA, and ED1+ macrophages and CD8+ T lymphocytes by immunohistochemistry. Statistical analysis was performed using ANOVA.

Results

MnTMPyP attenuated the IR-mediated increase in serum creatinine and circulating levels of interleukin (IL)-2 following 24 h of reperfusion. Furthermore, treatment attenuated increases in tissue levels of tumor necrosis factor (TNF)-α, IL-2, IL-4, and IL-13. MnTMPyP partially prevented the IR-induced infiltration of ED1+ macrophages and CD8+ T lymphocytes in the kidney. ATP depletion–recovery of porcine proximal tubular epithelial cells resulted in decreased IL-6 and IL-10 levels, and MnTMPyP partially restored these cytokines.

Conclusions

These results show that MnTMPyP is partially effective in reducing inflammation associated with renal IR and that reactive oxygen species play a role in modulating both pro- and anti-inflammatory pathways in acute kidney injury.

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Acknowledgments

The authors would like to thank Dr. Huanling Liang for technical assistance with this project. This study was partially supported by an AHA grant to Dr. Vani Nilakantan.

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Authors and Affiliations

  1. Division of Transplant Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA

    Jordan Mortensen, Brian Shames, Christopher P. Johnson & Vani Nilakantan

  2. Division of Clinical Research, Aurora Health Care, 1020 N. 12th Street, Suite 401, Milwaukee, WI, 53233, USA

    Brian Shames, Christopher P. Johnson & Vani Nilakantan

Authors
  1. Jordan Mortensen
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  2. Brian Shames
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  3. Christopher P. Johnson
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  4. Vani Nilakantan
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Corresponding author

Correspondence to Vani Nilakantan.

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Responsible Editor: Artur Bauhofer.

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Mortensen, J., Shames, B., Johnson, C.P. et al. MnTMPyP, a superoxide dismutase/catalase mimetic, decreases inflammatory indices in ischemic acute kidney injury. Inflamm. Res. 60, 299–307 (2011). https://doi.org/10.1007/s00011-010-0268-3

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  • DOI: https://doi.org/10.1007/s00011-010-0268-3

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