title: Protective effect of carbon monoxide donor compounds in endotoxin-induced acute renal failure.
abstract: BACKGROUND
  Sepsis is a common cause of acute renal failure (ARF) in clinical practice. However, the precise mechanism of endotoxin-induced ARF is not fully understood. There have been several reports that inhalation of carbon monoxide (CO) gas could be protective against acute rejection in intestine, lung, and kidney transplantation. Thus, we investigated the direct effect of CO in an experimental ARF model of septic shock induced by lipopolysaccharide (LPS).
  
  
  METHODS
  Mice were pretreated with [Ru(CO)3Cl2]2 (CO donor compounds) at various concentrations (0.5, 1.0 and 2.0 microg) which were intravenously injected 24 h before intraperitoneal LPS injection. Biomarkers including myeloperoxidase activity and histochemical staining were evaluated.
  
  
  RESULTS
  The elevation of plasma creatinine was suppressed in CO donor-pretreated mice compared with vehicle-treated mice (creatinine 0.35 vs. 0.25; p < 0.05) 24 h after LPS injection. Renal myeloperoxidase activity slightly decreased in CO donor-pretreated mice. In the histological examination, neutrophil infiltration was significantly diminished in CO donor-treated mice. Real-time polymerase chain reaction revealed significant improvements in inflammatory related genes, such as TNFalpha, MCP-1, RANTES and IL4.
  
  
  CONCLUSIONS
  Our results suggest the protective effect of the CO donor against endotoxin-induced renal injury; however, further study is needed to elucidate the mechanism.
authors.affiliation: Department of Medicine IV, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Shiohira
authors.forename: Takumi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Satsuki
authors.initials: S
authors.lastname: Shirota
authors.forename: Ken
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism*; D000818:Animals; D001806:Blood Urea Nitrogen; D002248:Carbon Monoxide / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004731:Endotoxins; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D004731:Endotoxins; D018836:Inflammation Mediators; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D002248:Carbon Monoxide; D003404:Creatinine; D009195:Peroxidase