MnTMPyP, a superoxide dismutase/catalase mimetic, decreases inflammatory indices in ischemic acute kidney injury
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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.
Cytokines were analyzed by ELISA, and ED1+ macrophages and CD8+ T lymphocytes by immunohistochemistry. Statistical analysis was performed using ANOVA.
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.
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.
KeywordsIschemia–reperfusion Kidney Reactive oxygen Inflammatory cytokines TNF MnTMPyP
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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