Novel pharmacological effects of lecithinized superoxide dismutase on ischemia/reperfusion injury in the kidneys of mice

• Published in: Life sciences (1973) 2022-01, Vol.288, p.120164-120164, Article 120164
• Main Authors: Tanaka, Ken-ichiro, Shimoda, Mikako, Kubota, Maho, Takafuji, Ayaka, Kawahara, Masahiro, Mizushima, Tohru
• Format: Article
• Language: English
• Subjects: Actin; Acute Kidney Injury - etiology; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Acute Kidney Injury - prevention & control; Animal models; Animals; Chemical compounds; Collagen; Creatinine; Diet, High-Fat; Disease Models, Animal; Fibrosis; Fibrosis - etiology; Fibrosis - metabolism; Fibrosis - pathology; Fibrosis - prevention & control; Gelatinase; High fat diet; Injuries; Interleukin 6; Intravenous administration; Ischemia; Ischemia/reperfusion; Kidney; Kidney diseases; Kidneys; Leukocytes (neutrophilic); Lipocalin; Male; Markers; Mice; Mice, Inbred ICR; Mouse devices; Muscles; Necrosis; Oxidation; Oxidative Stress; Pharmacology; Phosphatidylcholines - administration & dosage; Reactive oxygen species; Reactive Oxygen Species - metabolism; Renal; Reperfusion; Reperfusion Injury - complications; Smooth muscle; Superoxide dismutase; Superoxide Dismutase - administration & dosage; Urea
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.120164

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.