title: MnTMPyP, a superoxide dismutase/catalase mimetic, decreases inflammatory indices in ischemic acute kidney injury.
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).
  
  
  METHODS
  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.affiliation: Division of Transplant Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Mortensen
authors.forename: Brian
authors.initials: B
authors.lastname: Shames
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Johnson
authors.forename: Vani
authors.initials: V
authors.lastname: Nilakantan
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000473:pathology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism*; D013552:Swine
chemical_list: D016207:Cytokines; D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D002374:Catalase; D013482:Superoxide Dismutase