Carbon monoxide rescues the developmental lethality of experimental rat models of rhabdomyolysis-induced acute kidney injury

Many victims, after being extricated from a collapsed building as the result of a disaster, suffer from disaster nephrology, a term that is referred to as the crush syndrome (CS). Recommended treatments, which include dialysis or the continuous administration of massive amounts of fluid are not usually easy in cases of such mass natural disasters. In the present study, we examined the therapeutic performance of a biomimetic carbon monoxide (CO) delivery system, CO-enriched red blood cells (CO-RBCs), on experimental animal models of an acute kidney injury (AKI) induced by traumatic and nontraumatic rhabdomyolysis, including CS and rhabdomyolysis with massive hemorrhage shock. A single CO-RBC treatment was found to effectively suppress the pathogenesis of AKI with the mortality in these model rats being improved. In addition, in further studies using glycerol-induced rhabdomyolysis model rats, the pathogenesis of which is similar to that for the CS, AKI and mortality were also reduced as the result of a CO-RBC treatment. Furthermore, CO-RBCs were found to have renoprotective effects via the suppression of subsequent heme protein-associated renal oxidative injury; the oxidation of myoglobin in the kidneys, the generation of reactive oxygen species by free heme produced from degraded-cytochrome P450 and hemoglobin-associated renal injury. Because CO-RBCs can be prepared and used at both hospitals and at a disaster site, these findings suggest that CO-RBCs have the potential for use as a novel cell therapy against both nontraumatic and traumatic rhabdomyolysis including CS-induced AKI.