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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