Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice
| Autor: | Yuto Hiramoto, Kento Nishida, Toru Maruyama, Masako Miyahisa, Masaki Otagiri, Hiroshi Watanabe, Hiroto Nosaki, Rui Fujimura, Hitoshi Maeda |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Anti-Inflammatory Agents lcsh:Medicine Apoptosis Pharmacology medicine.disease_cause urologic and male genital diseases Kidney Antioxidants Mice Thioredoxins Medicine lcsh:Science Lung Multidisciplinary Acute kidney injury Acute Kidney Injury female genital diseases and pregnancy complications medicine.anatomical_structure Reperfusion Injury Oxidation-Reduction animal structures Respiratory distress syndrome Acute Lung Injury Lung injury Article Animals Survival rate Macrophage Migration-Inhibitory Factors Serum Albumin business.industry urogenital system Interleukin-6 Tumor Necrosis Factor-alpha lcsh:R medicine.disease body regions Mice Inbred C57BL Disease Models Animal Oxidative Stress Delayed-Action Preparations Drug delivery Macrophage migration inhibitory factor lcsh:Q business Reactive Oxygen Species Oxidative stress |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2045-2322 |
| Popis: | The mortality of patients with acute kidney injury (AKI) remains high due to AKI associated-lung injury. An effective strategy for preventing both AKI and AKI-associated lung injury is urgently needed. Thioredoxin-1 (Trx) is a redox-active protein that possesses anti-oxidative, anti-apoptotic and anti-inflammatory properties including modulation of macrophage migration inhibitory factor (MIF), but its short half-life limits its clinical application. Therefore, we examined the preventive effect of a long-acting Trx, which is a fusion protein of albumin and Trx (HSA-Trx), against AKI and AKI-associated lung injury. Recombinant HSA-Trx was expressed using a Pichia expression system. AKI-induced lung injury mice were generated by bilateral renal ischemia reperfusion injury (IRI). HSA-Trx administration attenuated renal IRI and its-associated lung injury. Both renal and pulmonary oxidative stress were suppressed by HSA-Trx. Moreover, HSA-Trx inhibited elevations of plasma IL-6 and TNF-α level, and suppressed IL-6–CXCL1/2-mediated neutrophil infiltration into lung and TNF-α-mediated pulmonary apoptosis. Additionally, HSA-Trx suppressed renal IRI-induced MIF expression in kidney and lung. Administration of HSA-Trx resulted in a significant increase in the survival rate of renal IRI mice. Collectively, HSA-Trx could have therapeutic utility in preventing both AKI and AKI-associated lung injury as a consequence of its systemic and sustained multiple biological action. |
| Databáze: | OpenAIRE |
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