Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice

Abstract

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.

Bergenin Monohydrate Attenuates Inflammatory Response via MAPK and NF-κB Pathways Against Klebsiella pneumonia Infection

“…In 2020, IL-1β, IL-6, and other proteins were found to be correlated with pulmonary inflammation with extensive lung involvement, as seen in COVID-19 patients. TNF-α improves the levels of PEG2 and bradykinin, which are also thought to influence the TNF-α/TNF receptor signaling pathway and promote the development of pulmonary endothelial cell injury ( Nishida et al, 2020 ). In 2018, a study reported that knockdown of TNF-α alleviated the severity of lung injury; thus, TNF-α might be a key target in injury and repair related to the lung ( Qi et al, 2018 ).…”

Probiotics partially attenuate the severity of acute kidney injury through an immunomodulatory effect

“…These findings demonstrated the beneficial effects of probiotics may in part be a function of reduced systemic inflammation. Nishida et al [ 25 ] demonstrated that the renoprotective effect of recombinant thioredoxin-1 and albumin fusion protein in IRI also influenced AKI-associated distant organ injury, including injury to the lung and liver. Similarly, the renoprotective effect of probiotic supplementation reduced AKI-related liver injury in our study.…”

Association of C5a/C5aR pathway to activate ERK1/2 and p38 MAPK in acute kidney injury – a mouse model

“…With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a plethora of evidence have demonstrated that AKI is very common among patients with COVID-19 (coronavirus disease 2019), occurring in approximately more than 50% of ICU (intensive care unit) patients (4)(5)(6)(7)(8). The extremely high rates of mortality could be the development of distant organ injury (9). It should not be considered as a single disease (10), when AKI appears, the primary task is to determine the etiology as soon as possible.…”