Abstract
Sulodexide is a potent antithrombin agent, however, whether it has beneficial effects on renal ischemia-reperfusion injury (IRI) remains unknown. In the present study, we assessed the therapeutic effects of sulodexide in renal IRI and tried to investigate the potential mechanism. One dose of sulodexide was injected intravenously in Sprague-Dawley rats 30 min before bilateral kidney ischemia for 45 min. The animals were sacrificed at 3h and 24h respectively. Our results showed that sulodexide pretreatment improved renal dysfunction and alleviated tubular pathological injury at 24h after reperfusion, which was accompanied with inhibition of oxidative stress, inflammation and cell apoptosis. Moreover, we noticed that antithrombin III (ATIII) was activated at 3h after reperfusion, which preceded the alleviation of renal injury. For in vitro study, hypoxia/reoxygenation (H/R) injury model for HK2 cells was carried out and apoptosis and reactive oxygen species (ROS) levels were evaluated after sulodexide pretreatment. Consistently, sulodexide pretreatment could reduce apoptosis and ROS level in HK2 cells under H/R injury. Taken together, sulodexide pretreatment might attenuate renal IRI through inhibition of inflammation, oxidative stress and apoptosis, and activation of ATIII.
Highlights
Renal ischemia reperfusion injury (IRI) is commonly seen in various clinical settings such as kidney transplantation, hemorrhagic shock or cardiovascular surgery [1]
We found that the renal mRNA expression levels of tumor necrosis factor α (TNFα), monocyte chemotactic protein 1 (MCP-1) and intercellular cell adhesion molecule-1 (ICAM-1) in ischemia-reperfusion injury (IRI) rats were substantially increased compared with sham rats, which was blunted by sulodexide pretreatment (Figure 4)
We sought to assess the therapeutic effects of sulodexide on renal IRI and www.impactjournals.com/oncotarget investigate the potential mechanisms
Summary
Renal ischemia reperfusion injury (IRI) is commonly seen in various clinical settings such as kidney transplantation, hemorrhagic shock or cardiovascular surgery [1]. Numerous efforts had been made to avoid or alleviate renal IRI, the morbidity and mortality of ischemic acute kidney injury (AKI) still remains high [2]. It is urgent to identify novel preventive strategies to decrease AKI incidence and to improve clinical outcome. It has been established that the pathophysiology of AKI predominantly involves continued hypoperfusion, inflammation, oxidative stress, and tubular epithelial apoptosis [3,4,5]. Several studies have shown that microvascular thrombosis generation plays a pivotal role in the pathophysiology of AKI, and many antithrombin agents, such as heparin [6] and antithrombin III (ATIII) [7,8,9] could mitigate renal IRI. Pharmacological agents with multiple function such as anti-coagulation, anti-oxidative and anti-inflammation properties may be promising preventative strategies for AKI
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