title: Protective Effects of Antioxidant Peptide SS-31 Against Multiple Organ Dysfunctions During Endotoxemia.
abstract: Oxidative stress causes mitochondrial impairment, the failure of energy production, and consequent organ dysfunctions. The aim of the present study was to investigate the potential therapeutic effects of mitochondrial antioxidant SS-31 on sepsis-induced organ dysfunctions and to explore the possible mechanism. Sepsis was induced by cecal ligation and puncture. Immediately and at 5 h after the operation, SS-31 (5 mg/kg) or vehicle was administered intraperitoneally. The levels of organ dysfunctions, malondialdehyde, superoxide dismutase, proinflammatory cytokines, pulmonary wet-to-dry weight ratio, myeloperoxidase activity, histological scores, nuclear factor kappa B p65, inducible nitric oxide synthase, reactive oxygen species, adenosine triphosphate, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells were assessed at the indicated time points. The 7-day survival rate was estimated by the Kaplan-Meier method. In the present study, SS-31 treatment significantly improved sepsis-induced organ dysfunctions as evidenced by decreased histological scores, increased arterial partial oxygen tension, and deceased serum alanine aminotransferase, urea nitrogen, and creatinine levels, which was accompanied by decreased levels of malondialdehyde, tumor necrosis factor-alpha, pulmonary myeloperoxidase activity, nuclear factor kappa B p65, inducible nitric oxide synthase, reactive oxygen species, and TUNEL-positive cells. In conclusion, our data suggested that the protective effects of SS-31 on sepsis-induced organ dysfunctions were associated with the inhibition of proinflammatory cytokines, oxidative stress, and apoptosis.
authors.affiliation: Department of Anesthesiology and Intensive Care, Jintan Hospital, Jiangsu University, Changzhou, China.
authors.forename: Guoming
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan, Road, Nanjing, 210002, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan, Road, Nanjing, 210002, China.
authors.forename: Renqi
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Intensive Care, Jintan Hospital, Jiangsu University, Changzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology and Intensive Care, Jintan Hospital, Jiangsu University, Changzhou, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan, Road, Nanjing, 210002, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan, Road, Nanjing, 210002, China. jimuhuo2009@sina.com.
authors.forename: Muhuo
authors.initials: M
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan, Road, Nanjing, 210002, China. liweiyan1965@126.com.
authors.forename: Sihai
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D002432:Cecum / Q000601:surgery; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D019446:Endotoxemia / Q000188:drug therapy*; D004734:Energy Metabolism / Q000502:physiology; D007249:Inflammation / Q000188:drug therapy; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; D003404:Creatinine; D000410:Alanine Transaminase
keywords: apoptosis; inflammation; mitochondria; oxidative stress; sepsis