Journal
BRITISH JOURNAL OF ANAESTHESIA
Volume 110, Issue 3, Pages 472-480Publisher
ELSEVIER SCI LTD
DOI: 10.1093/bja/aes577
Keywords
co-enzyme Q10; interleukin-6; interleukin-10; melatonin; sepsis; tocopherol
Categories
Funding
- Medical Research Council [G0800149]
- MRC [MC_U105663142, G0800149] Funding Source: UKRI
- Medical Research Council [MC_U105663142, G0800149] Funding Source: researchfish
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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.
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