Carbon Monoxide Rescues the Developmental Lethality of Experimental Rat Models of Rhabdomyolysis-Induced Acute Kidney Injury
| Autor: | Hidehisa Sekijima, Toru Maruyama, Masafumi Fukagawa, Kazuya Ooi, Kento Nishida, Taisei Nagasaki, Masaki Otagiri, Shigeru Ogaki, Kazuaki Matsumoto, Kazuaki Taguchi, Hiroshi Watanabe, Yuki Enoki, Hiroki Yanagisawa, Yu Ishima, Hitoshi Maeda |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Nephrology medicine.medical_specialty Erythrocytes Swine medicine.medical_treatment Apoptosis Kidney Rhabdomyolysis Pathogenesis Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Internal medicine medicine Animals Crush syndrome Dialysis Pharmacology Carbon Monoxide business.industry Acute kidney injury Kidney metabolism Acute Kidney Injury medicine.disease Survival Analysis Disease Models Animal Oxidative Stress 030104 developmental biology Shock (circulatory) Anesthesia Molecular Medicine LLC-PK1 Cells Crush Syndrome medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 372(3) |
| ISSN: | 1521-0103 |
| Popis: | 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. SIGNIFICANCE STATEMENT: After mass natural and man-made disasters, people who are trapped in collapsed buildings are in danger of acute kidney injury (AKI), including crush syndrome (CS)-related AKI. This paper reports that carbon monoxide-enriched red blood cells (CO-RBCs), which can be prepared at both hospitals and disaster sites, dramatically suppressed the pathogenesis of CS-related AKI, thus improving mortality via suppressing heme protein-associated renal injuries. CO-RBCs have the potential for serving as a practical therapeutic agent against disaster nephrology associated with the CS. |
| Databáze: | OpenAIRE |
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