We are analyzing https://link.springer.com/article/10.1007/s00204-016-1692-0.

Title:
Mitochondria-targeted antioxidant Mito-Tempo protects against acetaminophen hepatotoxicity | Archives of Toxicology
Description:
Acetaminophen (APAP) hepatotoxicity is characterized by an extensive mitochondrial oxidant stress. However, its importance as a drug target has not been clarified. To investigate this, fasted C57BL/6J mice were treated with 300 mg/kg APAP and the mitochondria-targeted antioxidant Mito-Tempo (MT) was given 1.5 h later. APAP caused severe liver injury in mice, as indicated by the increase in plasma ALT activities and centrilobular necrosis. MT dose-dependently reduced the injury. Importantly, MT did not affect APAP-protein adducts formation, glutathione depletion or c-jun N-terminal kinase activation and its mitochondrial translocation. In contrast, hepatic glutathione disulfide and peroxynitrite formation were dose-dependently reduced by MT, indicating its effective mitochondrial oxidant stress scavenging capacity. Consequently, mitochondrial translocation of Bax and release of mitochondrial intermembrane proteins such as apoptosis-inducing factor were prevented, and nuclear DNA fragmentation was eliminated. To demonstrate the importance of mitochondria-specific antioxidant property of MT, we compared its efficacy with Tempo, which has the same pharmacological mode of action as MT but lacks the mitochondria targeting moiety. In contrast to the dramatic protection by MT, the same molar dose of Tempo did not significantly reduce APAP hepatotoxicity. In contrast, even a 3 h post-treatment with MT reduced 70 % of the injury, and the combination of MT with N-acetylcysteine (NAC) provided superior protection than NAC alone. We conclude that MT protects against APAP overdose in mice by attenuating the mitochondrial oxidant stress and preventing peroxynitrite formation and the subsequent mitochondrial dysfunction. MT is a promising therapeutic agent for APAP overdose patients.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

Education
Insurance
Health & Fitness

Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

No common CMS systems were detected on Link.springer.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of link.springer.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month

Based on our best estimate, this website will receive around 7,643,078 visitors per month in the current month.

check SE Ranking
check Ahrefs
check Similarweb
check Ubersuggest
check Semrush

How Does Link.springer.com Make Money? {💸}

We're unsure how the site profits.

Not every website is profit-driven; some are created to spread information or serve as an online presence. Websites can be made for many reasons. This could be one of them. Link.springer.com has a revenue plan, but it's either invisible or we haven't found it.

Keywords {🔍}

pubmed, article, google, scholar, cas, acetaminophen, jaeschke, hepatotoxicity, mitochondrial, toxicol, central, liver, mice, injury, pharmacol, oxidant, stress, acetaminopheninduced, mcgill, glutathione, bajt, appl, nacetylcysteine, sci, protects, farhood, apap, formation, dna, mitochondria, overdose, lemasters, protection, antioxidant, mitotempo, drug, peroxynitrite, hinson, exp, ther, cell, privacy, cookies, content, research, mitochondriatargeted, necrosis, translocation, hepatic, apoptosis,

Topics {✒️}

c-jun n-terminal kinase mitochondria-targeted antioxidant mito-tempo month download article/chapter mitochondria-specific antioxidant property ischemia/reperfusion oxidant stress acetaminophen-induced oxidant stress high-pressure liquid chromatography high-performance liquid chromatography mito-tempo protects n-acetylcysteine blunts recovery drug-induced liver injury fasted c57bl/6j mice acetaminophen-induced liver injury mitochondrial oxidant stress full article pdf emergency department visits mitochondria-targeted nitroxide article du fas receptor-mediated apoptosis mito-tempo nac acetaminophen-induced cell death mitochondrial intermembrane proteins mitochondria-derived activator related subjects mitochondrial permeability transition apoptosis-inducing factor yan hm privacy choices/manage cookies mitochondria targeting moiety acetaminophen-protein adducts macmillan-crow la budnitz ds nitrotyrosine-protein adducts cohen sd nuclear dna fragmentation manganese superoxide dismutase mt dose-dependently reduced article archives peroxynitrite-induced mitochondrial acetaminophen-induced hepatotoxicity acetaminophen covalent binding large genomic dna subsequent mitochondrial dysfunction acute liver injury oxidant stress benzyl alcohol protects acute liver failure liver-specific loss acetaminophen-induced necrosis hepatic mitochondrial respiration

Questions {❓}

Gujral JS, Knight TR, Farhood A, Bajt ML, Jaeschke H (2002) Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis?

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Mitochondria-targeted antioxidant Mito-Tempo protects against acetaminophen hepatotoxicity
         description:Acetaminophen (APAP) hepatotoxicity is characterized by an extensive mitochondrial oxidant stress. However, its importance as a drug target has not been clarified. To investigate this, fasted C57BL/6J mice were treated with 300 mg/kg APAP and the mitochondria-targeted antioxidant Mito-Tempo (MT) was given 1.5 h later. APAP caused severe liver injury in mice, as indicated by the increase in plasma ALT activities and centrilobular necrosis. MT dose-dependently reduced the injury. Importantly, MT did not affect APAP-protein adducts formation, glutathione depletion or c-jun N-terminal kinase activation and its mitochondrial translocation. In contrast, hepatic glutathione disulfide and peroxynitrite formation were dose-dependently reduced by MT, indicating its effective mitochondrial oxidant stress scavenging capacity. Consequently, mitochondrial translocation of Bax and release of mitochondrial intermembrane proteins such as apoptosis-inducing factor were prevented, and nuclear DNA fragmentation was eliminated. To demonstrate the importance of mitochondria-specific antioxidant property of MT, we compared its efficacy with Tempo, which has the same pharmacological mode of action as MT but lacks the mitochondria targeting moiety. In contrast to the dramatic protection by MT, the same molar dose of Tempo did not significantly reduce APAP hepatotoxicity. In contrast, even a 3 h post-treatment with MT reduced 70 % of the injury, and the combination of MT with N-acetylcysteine (NAC) provided superior protection than NAC alone. We conclude that MT protects against APAP overdose in mice by attenuating the mitochondrial oxidant stress and preventing peroxynitrite formation and the subsequent mitochondrial dysfunction. MT is a promising therapeutic agent for APAP overdose patients.
         datePublished:2016-03-22T00:00:00Z
         dateModified:2016-03-22T00:00:00Z
         pageStart:761
         pageEnd:773
         sameAs:https://doi.org/10.1007/s00204-016-1692-0
         keywords:
            Acetaminophen hepatotoxicity
            Mitochondria
            Oxidant stress
            Antioxidant
            Mito-Tempo
            Pharmacology/Toxicology
            Occupational Medicine/Industrial Medicine
            Environmental Health
            Biomedicine
            general
         image:
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig1_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig2_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig3_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig4_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig5_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig6_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig7_HTML.gif
         isPartOf:
            name:Archives of Toxicology
            issn:
               1432-0738
               0340-5761
            volumeNumber:91
            type:
               Periodical
               PublicationVolume
         publisher:
            name:Springer Berlin Heidelberg
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:Kuo Du
               affiliation:
                     name:University of Kansas Medical Center
                     address:
                        name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Anwar Farhood
               affiliation:
                     name:St. David’s North Austin Medical Center
                     address:
                        name:Department of Pathology, St. David’s North Austin Medical Center, Austin, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Hartmut Jaeschke
               url:http://orcid.org/0000-0002-8695-6980
               affiliation:
                     name:University of Kansas Medical Center
                     address:
                        name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
         isAccessibleForFree:
         hasPart:
            isAccessibleForFree:
            cssSelector:.main-content
            type:WebPageElement
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:Mitochondria-targeted antioxidant Mito-Tempo protects against acetaminophen hepatotoxicity
      description:Acetaminophen (APAP) hepatotoxicity is characterized by an extensive mitochondrial oxidant stress. However, its importance as a drug target has not been clarified. To investigate this, fasted C57BL/6J mice were treated with 300 mg/kg APAP and the mitochondria-targeted antioxidant Mito-Tempo (MT) was given 1.5 h later. APAP caused severe liver injury in mice, as indicated by the increase in plasma ALT activities and centrilobular necrosis. MT dose-dependently reduced the injury. Importantly, MT did not affect APAP-protein adducts formation, glutathione depletion or c-jun N-terminal kinase activation and its mitochondrial translocation. In contrast, hepatic glutathione disulfide and peroxynitrite formation were dose-dependently reduced by MT, indicating its effective mitochondrial oxidant stress scavenging capacity. Consequently, mitochondrial translocation of Bax and release of mitochondrial intermembrane proteins such as apoptosis-inducing factor were prevented, and nuclear DNA fragmentation was eliminated. To demonstrate the importance of mitochondria-specific antioxidant property of MT, we compared its efficacy with Tempo, which has the same pharmacological mode of action as MT but lacks the mitochondria targeting moiety. In contrast to the dramatic protection by MT, the same molar dose of Tempo did not significantly reduce APAP hepatotoxicity. In contrast, even a 3 h post-treatment with MT reduced 70 % of the injury, and the combination of MT with N-acetylcysteine (NAC) provided superior protection than NAC alone. We conclude that MT protects against APAP overdose in mice by attenuating the mitochondrial oxidant stress and preventing peroxynitrite formation and the subsequent mitochondrial dysfunction. MT is a promising therapeutic agent for APAP overdose patients.
      datePublished:2016-03-22T00:00:00Z
      dateModified:2016-03-22T00:00:00Z
      pageStart:761
      pageEnd:773
      sameAs:https://doi.org/10.1007/s00204-016-1692-0
      keywords:
         Acetaminophen hepatotoxicity
         Mitochondria
         Oxidant stress
         Antioxidant
         Mito-Tempo
         Pharmacology/Toxicology
         Occupational Medicine/Industrial Medicine
         Environmental Health
         Biomedicine
         general
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig1_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig2_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig3_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig4_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig5_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig6_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00204-016-1692-0/MediaObjects/204_2016_1692_Fig7_HTML.gif
      isPartOf:
         name:Archives of Toxicology
         issn:
            1432-0738
            0340-5761
         volumeNumber:91
         type:
            Periodical
            PublicationVolume
      publisher:
         name:Springer Berlin Heidelberg
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Kuo Du
            affiliation:
                  name:University of Kansas Medical Center
                  address:
                     name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Anwar Farhood
            affiliation:
                  name:St. David’s North Austin Medical Center
                  address:
                     name:Department of Pathology, St. David’s North Austin Medical Center, Austin, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Hartmut Jaeschke
            url:http://orcid.org/0000-0002-8695-6980
            affiliation:
                  name:University of Kansas Medical Center
                  address:
                     name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      isAccessibleForFree:
      hasPart:
         isAccessibleForFree:
         cssSelector:.main-content
         type:WebPageElement
["Periodical","PublicationVolume"]:
      name:Archives of Toxicology
      issn:
         1432-0738
         0340-5761
      volumeNumber:91
Organization:
      name:Springer Berlin Heidelberg
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:University of Kansas Medical Center
      address:
         name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
         type:PostalAddress
      name:St. David’s North Austin Medical Center
      address:
         name:Department of Pathology, St. David’s North Austin Medical Center, Austin, USA
         type:PostalAddress
      name:University of Kansas Medical Center
      address:
         name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Kuo Du
      affiliation:
            name:University of Kansas Medical Center
            address:
               name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
               type:PostalAddress
            type:Organization
      name:Anwar Farhood
      affiliation:
            name:St. David’s North Austin Medical Center
            address:
               name:Department of Pathology, St. David’s North Austin Medical Center, Austin, USA
               type:PostalAddress
            type:Organization
      name:Hartmut Jaeschke
      url:http://orcid.org/0000-0002-8695-6980
      affiliation:
            name:University of Kansas Medical Center
            address:
               name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
      name:Department of Pathology, St. David’s North Austin Medical Center, Austin, USA
      name:Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA
WebPageElement:
      isAccessibleForFree:
      cssSelector:.main-content

External Links {🔗}(207)

Analytics and Tracking {📊}

Google Tag Manager

Libraries {📚}

Clipboard.js
Prism.js

CDN Services {📦}

Crossref

4.09s.

LINK . SPRINGER . COM {}