Novel pharmacological effects of lecithinized superoxide dismutase on ischemia/reperfusion injury in the kidneys of mice
| Autor: | Tohru Mizushima, Masahiro Kawahara, Mikako Shimoda, Maho Kubota, Ayaka Takafuji, Ken Ichiro Tanaka |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Pharmacology urologic and male genital diseases medicine.disease_cause Diet High-Fat General Biochemistry Genetics and Molecular Biology Mice Fibrosis Renal fibrosis Medicine Animals General Pharmacology Toxicology and Pharmaceutics Kidney Mice Inbred ICR Renal ischemia business.industry Superoxide Dismutase Acute kidney injury General Medicine Acute Kidney Injury medicine.disease Disease Models Animal Oxidative Stress medicine.anatomical_structure Reperfusion Injury Phosphatidylcholines business Reactive Oxygen Species Reperfusion injury Oxidative stress Kidney disease |
| Zdroj: | Life sciences. 288 |
| ISSN: | 1879-0631 |
| Popis: | Renal ischemia/reperfusion (I/R) injury is a major clinical problem because it can cause acute kidney injury (AKI) or lead to the transition from AKI to chronic kidney disease (CKD). Oxidative stress, which involves the production of reactive oxygen species (ROS), plays an important role in the development and exacerbation of I/R-induced kidney injury. However, we have previously reported that lecithinized superoxide dismutase (PC-SOD), a SOD derivative with high tissue affinity and high stability in plasma, has beneficial effects in various disease models because of its inhibitory effect on ROS production. Therefore, we aimed to determine the effects of intravenous PC-SOD administration in a mouse model of renal injury induced by I/R. PC-SOD markedly ameliorated the I/R-induced increases in markers of renal damage (urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin, and interleukin-6) and tubular necrosis 48 h after the intervention. We also found that PC-SOD significantly ameliorated the I/R-induced increase in ROS production, using an ex vivo imaging system. Furthermore, PC-SOD inhibited the increases in expression of markers of fibrosis (α-smooth muscle actin and collagen 1A1) 96 h after, and renal fibrosis 25 days after I/R was induced. Finally, we found that PC-SOD ameliorated the I/R-induced AKI in mice with high-fat diet-induced prediabetes. These results suggest that PC-SOD inhibits AKI and the transition from AKI to CKD through the inhibition of ROS production. Therefore, we believe that PC-SOD may represent an effective therapeutic agent for I/R-induced renal injury. |
| Databáze: | OpenAIRE |
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