Sulodexide pretreatment attenuates renal ischemia-reperfusion injury in rats

// Jianyong Yin 1, * , Weibin Chen 2, * , Fenfen Ma 3, * , Zeyuan Lu 1 , Rui Wu 1 , Guangyuan Zhang 4 , Niansong Wang 1 , Feng Wang 1 1 Department of Nephrology, Shanghai Eighth People’s Hospital, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China 2 Department of Laboratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China 3 Department of Pharmacy, Shanghai Pudong Hospital, Shanghai 201399, China 4 Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, China * These authors have contributed equally to this work Correspondence to: Feng Wang, email: zyzwq1030@163.com Guangyuan Zhang, email: zgy0879@qq.com Keywords: sulodexide, ischemia-reperfusion, antithrombin III, oxidative stress, apoptosis Received: November 08, 2016     Accepted: December 13, 2016     Published: December 27, 2016 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.