title: SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model.
abstract: Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI.
authors.affiliation: Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China.
authors.forename: Youguang
authors.identifier: 0000-0002-5162-6631
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qin
authors.identifier: 0000-0002-0888-7668
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Siwei
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhongqing
authors.identifier: 0000-0003-2482-949X
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Critical Care Medicine, Institute of Translational Medicine, The First People's Hospital of Chenzhou, Hunan, Chenzhou, China.
authors.forename: Xingui
authors.initials: X
authors.lastname: Dai
authors.affiliation: Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China; Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhenhua
authors.identifier: 0000-0002-9509-1536
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ke-Seng
authors.identifier: 0000-0002-1071-5232
authors.initials: KS
authors.lastname: Zhao
mesh_terms: D000107:Acetylation; D058186:Acute Kidney Injury / Q000201:enzymology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D002432:Cecum / Q000382:microbiology / Q000601:surgery; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008026:Ligation; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011677:Punctures; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D018805:Sepsis / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
chemical_list: D002227:Carbazoles; D056572:Histone Deacetylase Inhibitors; D000077185:Resveratrol; D056564:Sirtuin 1; D037761:Sirtuins; D013267:Stilbenes; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; C000607791:SIRT3 protein, rat; C488368:Sirt1 protein, rat