title: Sulodexide pretreatment attenuates renal ischemia-reperfusion injury in rats.
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.
authors.affiliation: Department of Nephrology, Shanghai Eighth People's Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Laboratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Shanghai Pudong Hospital, Shanghai 201399, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Nephrology, Shanghai Eighth People's Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Zeyuan
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Nephrology, Shanghai Eighth People's Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Shanghai Eighth People's Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shanghai Eighth People's Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D000990:Antithrombin III / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D019610:Cytoprotection; D004195:Disease Models, Animal; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D006025:Glycosaminoglycans; D017382:Reactive Oxygen Species; C007858:glucuronyl glucosamine glycan sulfate; D000990:Antithrombin III
keywords: antithrombin III; apoptosis; ischemia-reperfusion; oxidative stress; sulodexide