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MnTMPyP, a superoxide dismutase/catalase mimetic, decreases inflammatory indices in ischemic acute kidney injury. Inflamm Res 2011 Mar;60(3):299-307

Date

12/15/2010

Pubmed ID

21153678

DOI

10.1007/s00011-010-0268-3

Scopus ID

2-s2.0-79951727139   13 Citations

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.

Author List

Mortensen J, Shames B, Johnson CP, Nilakantan V

Author

Christopher P. Johnson MD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Adenosine Triphosphate
Animals
Catalase
Cells, Cultured
Cytokines
Inflammation
Kidney
Kidney Tubules
Male
Metalloporphyrins
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
Reperfusion Injury
Superoxide Dismutase
Swine
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00