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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.IR

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.

Authors+Show Affiliations

Division of Transplant Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21153678

Citation

Mortensen, Jordan, et al. "MnTMPyP, a Superoxide Dismutase/catalase Mimetic, Decreases Inflammatory Indices in Ischemic Acute Kidney Injury." Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], vol. 60, no. 3, 2011, pp. 299-307.
Mortensen J, Shames B, Johnson CP, et al. MnTMPyP, a superoxide dismutase/catalase mimetic, decreases inflammatory indices in ischemic acute kidney injury. Inflamm Res. 2011;60(3):299-307.
Mortensen, J., Shames, B., Johnson, C. P., & Nilakantan, V. (2011). MnTMPyP, a superoxide dismutase/catalase mimetic, decreases inflammatory indices in ischemic acute kidney injury. Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], 60(3), 299-307. https://doi.org/10.1007/s00011-010-0268-3
Mortensen J, et al. MnTMPyP, a Superoxide Dismutase/catalase Mimetic, Decreases Inflammatory Indices in Ischemic Acute Kidney Injury. Inflamm Res. 2011;60(3):299-307. PubMed PMID: 21153678.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MnTMPyP, a superoxide dismutase/catalase mimetic, decreases inflammatory indices in ischemic acute kidney injury. AU - Mortensen,Jordan, AU - Shames,Brian, AU - Johnson,Christopher P, AU - Nilakantan,Vani, Y1 - 2010/12/12/ PY - 2010/03/12/received PY - 2010/10/04/accepted PY - 2010/08/18/revised PY - 2010/12/15/entrez PY - 2010/12/15/pubmed PY - 2011/6/28/medline SP - 299 EP - 307 JF - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JO - Inflamm Res VL - 60 IS - 3 N2 - 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. SN - 1420-908X UR - https://www.unboundmedicine.com/medline/citation/21153678/MnTMPyP_a_superoxide_dismutase/catalase_mimetic_decreases_inflammatory_indices_in_ischemic_acute_kidney_injury_ L2 - https://dx.doi.org/10.1007/s00011-010-0268-3 DB - PRIME DP - Unbound Medicine ER -