Protective effect of carbon monoxide donor compounds in endotoxin-induced acute renal failure.

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).

Method: 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.

Conclusion: Our results suggest the protective effect of the CO donor against endotoxin-induced renal injury; however, further study is needed to elucidate the mechanism.