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
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...
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| Veröffentlicht in: | British journal of anaesthesia : BJA 2013-03, Vol.110 (3), p.472-480 |
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| creator | Lowes, D.A. Webster, N.R. Murphy, M.P. Galley, H.F. |
| description | 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 (P |
| doi_str_mv | 10.1093/bja/aes577 |
| format | Article |
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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 (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001).
Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.</description><identifier>ISSN: 0007-0912</identifier><identifier>EISSN: 1471-6771</identifier><identifier>DOI: 10.1093/bja/aes577</identifier><identifier>PMID: 23381720</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Acute Disease ; Alanine ; Animal models ; Animals ; Antioxidants ; Antioxidants - pharmacology ; Antioxidants - therapeutic use ; Biochemical markers ; Biomarkers ; Blood ; co-enzyme Q10 ; Creatinine ; Cytokines - biosynthesis ; Electron transport ; Escherichia coli ; Inflammation ; Interleukin 6 ; interleukin-10 ; Interleukin-6 - metabolism ; Kidney Function Tests ; Lipopolysaccharides ; Liver Function Tests ; Male ; Melatonin ; Melatonin - pharmacology ; Melatonin - therapeutic use ; Mitochondria ; Mitochondria - drug effects ; Multiple Organ Failure - physiopathology ; Multiple Organ Failure - prevention & control ; Organophosphorus Compounds - therapeutic use ; Oxidative stress ; Oxidative Stress - drug effects ; Oxygen Consumption - drug effects ; peptidoglycans ; Rats ; Rats, Sprague-Dawley ; Sepsis ; Sepsis - chemically induced ; Sepsis - drug therapy ; Sepsis - physiopathology ; Staphylococcus aureus ; tocopherol ; Translational Research ; Ubiquinone - analogs & derivatives ; Ubiquinone - therapeutic use</subject><ispartof>British journal of anaesthesia : BJA, 2013-03, Vol.110 (3), p.472-480</ispartof><rights>2013 The Author(s)</rights><rights>The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-19e3ac6bf21b9f89fc602fada35ad015ad7adfcde2cf5968908a3d5d7f0b01a03</citedby><cites>FETCH-LOGICAL-c527t-19e3ac6bf21b9f89fc602fada35ad015ad7adfcde2cf5968908a3d5d7f0b01a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23381720$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lowes, D.A.</creatorcontrib><creatorcontrib>Webster, N.R.</creatorcontrib><creatorcontrib>Murphy, M.P.</creatorcontrib><creatorcontrib>Galley, H.F.</creatorcontrib><title>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</title><title>British journal of anaesthesia : BJA</title><addtitle>Br J Anaesth</addtitle><addtitle>Br J Anaesth</addtitle><description>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 (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001).
Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.</description><subject>Acute Disease</subject><subject>Alanine</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Antioxidants - therapeutic use</subject><subject>Biochemical markers</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>co-enzyme Q10</subject><subject>Creatinine</subject><subject>Cytokines - biosynthesis</subject><subject>Electron transport</subject><subject>Escherichia coli</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>interleukin-10</subject><subject>Interleukin-6 - metabolism</subject><subject>Kidney Function Tests</subject><subject>Lipopolysaccharides</subject><subject>Liver Function Tests</subject><subject>Male</subject><subject>Melatonin</subject><subject>Melatonin - pharmacology</subject><subject>Melatonin - therapeutic use</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Multiple Organ Failure - physiopathology</subject><subject>Multiple Organ Failure - prevention & control</subject><subject>Organophosphorus Compounds - therapeutic use</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxygen Consumption - drug effects</subject><subject>peptidoglycans</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sepsis</subject><subject>Sepsis - chemically induced</subject><subject>Sepsis - drug therapy</subject><subject>Sepsis - physiopathology</subject><subject>Staphylococcus aureus</subject><subject>tocopherol</subject><subject>Translational Research</subject><subject>Ubiquinone - analogs & derivatives</subject><subject>Ubiquinone - therapeutic use</subject><issn>0007-0912</issn><issn>1471-6771</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9ks1u1DAUhS0EokNhwwMgb5AQaqgdT-JkU6mq-JMqsYG1dWNfd9wm9mA7I_p-PBieZloVCbGJY_k751z5mJDXnH3grBenwzWcAqZGyidkxdeSV62U_ClZMcZkxXpeH5EXKV0zxmXdN8_JUS1EV_7Zivw-99mFX86Az4nmDWS6jSGjznRyOehN8CY6oBHNrJE6nzGOON84X7UUvKF32ux2SFOOmNIJdVNxKPvH-pHa2euS5E_uVAe7wRUCJ6cLMEG8wZhosDTEK_DU3KZ7UcmlZYYy3BQMjnsG9JxLJm6TSy_JMwtjwleH9Zj8-PTx-8WX6vLb568X55eVbmqZK96jAN0OtuZDb7ve6pbVFgyIBgzj5SPBWG2w1rbp265nHQjTGGnZwDgwcUzOFt_tPExoNPocYVTb6MrwtyqAU3-feLdRV2GnRCMZa7ti8O5gEMPPGVNWk0saxxE8hjkpLmrRsXa93qPvF1THkFJE-xDDmdrXrkrtaqm9wG8eD_aA3vdcgLcLEObt_43WC4flGncOo0raoddoXCxvQpng_iX7Axqc0Kw</recordid><startdate>20130301</startdate><enddate>20130301</enddate><creator>Lowes, D.A.</creator><creator>Webster, N.R.</creator><creator>Murphy, M.P.</creator><creator>Galley, H.F.</creator><general>Elsevier Ltd</general><general>Oxford University Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>20130301</creationdate><title>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</title><author>Lowes, D.A. ; Webster, N.R. ; Murphy, M.P. ; Galley, H.F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c527t-19e3ac6bf21b9f89fc602fada35ad015ad7adfcde2cf5968908a3d5d7f0b01a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute Disease</topic><topic>Alanine</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Antioxidants - therapeutic use</topic><topic>Biochemical markers</topic><topic>Biomarkers</topic><topic>Blood</topic><topic>co-enzyme Q10</topic><topic>Creatinine</topic><topic>Cytokines - biosynthesis</topic><topic>Electron transport</topic><topic>Escherichia coli</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>interleukin-10</topic><topic>Interleukin-6 - metabolism</topic><topic>Kidney Function Tests</topic><topic>Lipopolysaccharides</topic><topic>Liver Function Tests</topic><topic>Male</topic><topic>Melatonin</topic><topic>Melatonin - pharmacology</topic><topic>Melatonin - therapeutic use</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Multiple Organ Failure - physiopathology</topic><topic>Multiple Organ Failure - prevention & control</topic><topic>Organophosphorus Compounds - therapeutic use</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxygen Consumption - drug effects</topic><topic>peptidoglycans</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sepsis</topic><topic>Sepsis - chemically induced</topic><topic>Sepsis - drug therapy</topic><topic>Sepsis - physiopathology</topic><topic>Staphylococcus aureus</topic><topic>tocopherol</topic><topic>Translational Research</topic><topic>Ubiquinone - analogs & derivatives</topic><topic>Ubiquinone - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lowes, D.A.</creatorcontrib><creatorcontrib>Webster, N.R.</creatorcontrib><creatorcontrib>Murphy, M.P.</creatorcontrib><creatorcontrib>Galley, H.F.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Access via Oxford University Press (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of anaesthesia : BJA</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lowes, D.A.</au><au>Webster, N.R.</au><au>Murphy, M.P.</au><au>Galley, H.F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>British journal of anaesthesia : BJA</jtitle><stitle>Br J Anaesth</stitle><addtitle>Br J Anaesth</addtitle><date>2013-03-01</date><risdate>2013</risdate><volume>110</volume><issue>3</issue><spage>472</spage><epage>480</epage><pages>472-480</pages><issn>0007-0912</issn><eissn>1471-6771</eissn><abstract>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 (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001).
Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>23381720</pmid><doi>10.1093/bja/aes577</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acute Disease Alanine Animal models Animals Antioxidants Antioxidants - pharmacology Antioxidants - therapeutic use Biochemical markers Biomarkers Blood co-enzyme Q10 Creatinine Cytokines - biosynthesis Electron transport Escherichia coli Inflammation Interleukin 6 interleukin-10 Interleukin-6 - metabolism Kidney Function Tests Lipopolysaccharides Liver Function Tests Male Melatonin Melatonin - pharmacology Melatonin - therapeutic use Mitochondria Mitochondria - drug effects Multiple Organ Failure - physiopathology Multiple Organ Failure - prevention & control Organophosphorus Compounds - therapeutic use Oxidative stress Oxidative Stress - drug effects Oxygen Consumption - drug effects peptidoglycans Rats Rats, Sprague-Dawley Sepsis Sepsis - chemically induced Sepsis - drug therapy Sepsis - physiopathology Staphylococcus aureus tocopherol Translational Research Ubiquinone - analogs & derivatives Ubiquinone - therapeutic use |
| title | 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 |
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