PMID- 26484460 OWN - NLM STAT- MEDLINE DCOM- 20160210 LR - 20220317 IS - 1526-7598 (Electronic) IS - 0003-2999 (Linking) VI - 121 IP - 5 DP - 2015 Nov TI - Polydatin Inhibits Mitochondrial Dysfunction in the Renal Tubular Epithelial Cells of a Rat Model of Sepsis-Induced Acute Kidney Injury. PG - 1251-60 LID - 10.1213/ANE.0000000000000977 [doi] AB - BACKGROUND: Mitochondrial injury is a major cause of sepsis-induced organ failure. Polydatin (PD), a natural polyphenol, demonstrates protective mitochondrial effects in neurons and arteriolar smooth muscle cells during severe shock. In this study, we investigated the effects of PD on renal tubular epithelial cell (RTEC) mitochondria in a rat model of sepsis-induced acute kidney injury. METHODS: Rats underwent cecal ligation and puncture (CLP) to mimic sepsis-induced acute kidney injury. Rats were randomly divided into sham, CLP + normal saline, CLP + vehicle, and CLP + PD groups. Normal saline, vehicle, and 30 mg/kg PD were administered at 6, 12, and 18 hours after CLP or sham surgery via the tail vein. Mitochondrial morphology, metabolism, and function in RTECs were then assessed. Serum cytokines, renal function, survival, and histologic changes in the kidney were also evaluated. RESULTS: CLP increased lipid peroxide content, lysosomal instability, and opening of the mitochondrial permeability transition pore and caused mitochondrial swelling. Moreover, mitochondrial membrane potential (DeltaPsim) was decreased and ATP levels reduced after CLP. PD inhibited all the above effects. It also inhibited the inflammatory response, improved renal function, attenuated histologic indicators of kidney damage, and prolonged survival. CONCLUSIONS: PD protects RTECs against mitochondrial dysfunction and prolongs survival in a rat model of sepsis-induced acute kidney injury. These effects may partially result from reductions in interleukin-6 and oxidative stress. FAU - Gao, Youguang AU - Gao Y AD - From the *Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P.R. China; daggerDepartment of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, P.R. China; double daggerDepartment of Pathophysiology, Southern Medical University, Guangzhou, Guangdong Province, P.R. China; section signDepartment of Critical Care Medicine, The First People's Hospital of Chenzhou, Chenzhou, Hunan, China; parallelInstitute of Translation Medicine, University of South China, Hunan Province, China; and paragraph signDepartment of Pathology, Maternal and Child Health Hospital of Liuzhou, Liu Zhou, Guangxi Province, P.R. China. FAU - Zeng, Zhenhua AU - Zeng Z FAU - Li, Tao AU - Li T FAU - Xu, Siqi AU - Xu S FAU - Wang, Xingmin AU - Wang X FAU - Chen, Zhongqing AU - Chen Z FAU - Lin, Caizhu AU - Lin C LA - eng PT - Journal Article PL - United States TA - Anesth Analg JT - Anesthesia and analgesia JID - 1310650 RN - 0 (Drugs, Chinese Herbal) RN - 0 (Glucosides) RN - 0 (Stilbenes) RN - XM261C37CQ (polydatin) SB - IM MH - Acute Kidney Injury/*drug therapy/etiology/pathology MH - Animals MH - *Disease Models, Animal MH - Drugs, Chinese Herbal/pharmacology/therapeutic use MH - Epithelial Cells/*drug effects/pathology/physiology MH - Glucosides/pharmacology/*therapeutic use MH - Kidney Tubules/*drug effects/pathology/physiology MH - Membrane Potential, Mitochondrial/drug effects/physiology MH - Mitochondria/*drug effects/physiology MH - Rats MH - Rats, Sprague-Dawley MH - Sepsis/complications/*drug therapy/pathology MH - Stilbenes/pharmacology/*therapeutic use EDAT- 2015/10/21 06:00 MHDA- 2016/02/11 06:00 CRDT- 2015/10/21 06:00 PHST- 2015/10/21 06:00 [entrez] PHST- 2015/10/21 06:00 [pubmed] PHST- 2016/02/11 06:00 [medline] AID - 00000539-201511000-00021 [pii] AID - 10.1213/ANE.0000000000000977 [doi] PST - ppublish SO - Anesth Analg. 2015 Nov;121(5):1251-60. doi: 10.1213/ANE.0000000000000977.