Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

被引:258
作者
Lowes, D. A. [1 ]
Webster, N. R. [1 ]
Murphy, M. P. [2 ]
Galley, H. F. [1 ]
机构
[1] Univ Aberdeen, Sch Med & Dent, Acad Unit Anaesthesia & Intens Care, Aberdeen, Scotland
[2] MRC, Mitochondrial Biol Unit, Cambridge, England
基金
英国医学研究理事会;
关键词
co-enzyme Q10; interleukin-6; interleukin-10; melatonin; sepsis; tocopherol; TARGETED ANTIOXIDANTS; MELATONIN TREATMENT; NITRIC-OXIDE; IN-VIVO; INFLAMMATION; DAMAGE; PEROXYNITRITE; INHIBITION; LIVER; MITOQ;
D O I
10.1093/bja/aes577
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage. Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines. MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P0.002), reduced oxidative stress (P0.02), and decreased interleukin-6 levels (P0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P0.02) and creatinine concentrations (P0.0001). Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.
引用
收藏
页码:472 / 480
页数:9
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