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Succinate prodrugs ...
Succinate prodrugs in combination with atropine and pralidoxime protect cerebral mitochondrial function in a rodent model of acute organophosphate poisoning
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- Piel, Sarah (författare)
- The Children's Hospital of Philadelphia
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- Janowska, Joanna I. (författare)
- The Children's Hospital of Philadelphia
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- Ward, J. Laurenson (författare)
- The Children's Hospital of Philadelphia
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- McManus, Meagan J. (författare)
- The Children's Hospital of Philadelphia
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- Jose, Joshua S. (författare)
- The Children's Hospital of Philadelphia
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- Starr, Jonathan (författare)
- The Children's Hospital of Philadelphia
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- Sheldon, Malkah (författare)
- The Children's Hospital of Philadelphia
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- Clayman, Carly L. (författare)
- The Children's Hospital of Philadelphia
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- Elmér, Eskil (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,Abliva AB
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- Hansson, Magnus J. (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,Abliva AB
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- Jang, David H. (författare)
- University of Pennsylvania
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- Karlsson, Michael (författare)
- Copenhagen University Hospital
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- Ehinger, Johannes K. (författare)
- Lund University,Lunds universitet,Öron-, näs- och halssjukdomar, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Otorhinolaryngology (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Mitochondrial Medicine,Lund University Research Groups,Skåne University Hospital
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- Kilbaugh, Todd J. (författare)
- The Children's Hospital of Philadelphia
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(creator_code:org_t)
- 2022-11-25
- 2022
- Engelska.
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Pesticides account for hundreds of millions of cases of acute poisoning worldwide each year, with organophosphates (OPs) being responsible for the majority of all pesticide-related deaths. OPs inhibit the enzyme acetylcholinesterase (AChE), which leads to impairment of the central- and peripheral nervous system. Current standard of care (SOC) alleviates acute neurologic-, cardiovascular- and respiratory symptoms and reduces short term mortality. However, survivors often demonstrate significant neurologic sequelae. This highlights the critical need for further development of adjunctive therapies with novel targets. While the inhibition of AChE is thought to be the main mechanism of injury, mitochondrial dysfunction and resulting metabolic crisis may contribute to the overall toxicity of these agents. We hypothesized that the mitochondrially targeted succinate prodrug NV354 would support mitochondrial function and reduce brain injury during acute intoxication with the OP diisopropylfluorophosphate (DFP). To this end, we developed a rat model of acute DFP intoxication and evaluated the efficacy of NV354 as adjunctive therapy to SOC treatment with atropine and pralidoxime. We demonstrate that NV354, in combination with atropine and pralidoxime therapy, significantly improved cerebral mitochondrial complex IV-linked respiration and reduced signs of brain injury in a rodent model of acute DFP exposure.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Piel, Sarah
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Janowska, Joanna ...
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Ward, J. Laurens ...
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McManus, Meagan ...
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Jose, Joshua S.
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Starr, Jonathan
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visa fler...
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Sheldon, Malkah
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Clayman, Carly L ...
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Elmér, Eskil
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Hansson, Magnus ...
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Jang, David H.
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Karlsson, Michae ...
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Ehinger, Johanne ...
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Kilbaugh, Todd J ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Farmakologi och ...
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Scientific Repor ...
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Lunds universitet