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Cell-Free DNA as a ...
Cell-Free DNA as a Biomarker in a Rodent Model of Chlorpyrifos Poisoning Causing Mitochondrial Dysfunction
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- Kao, Shih Han (författare)
- The Children's Hospital of Philadelphia
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- Shofer, Frances S. (författare)
- University of Pennsylvania
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- Greenwood, John C. (författare)
- University of Pennsylvania
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- Alomaja, Oladunni (författare)
- University of Pennsylvania
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- Ranganathan, Abhay (författare)
- The Children's Hospital of Philadelphia
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- Piel, Sarah (författare)
- The Children's Hospital of Philadelphia
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- Mesaros, Clementina (författare)
- University of Pennsylvania
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- Shin, Samuel S. (författare)
- University of Pennsylvania
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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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- Jang, David H. (författare)
- University of Pennsylvania
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(creator_code:org_t)
- 2023
- 2023
- Engelska 10 s.
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Ingår i: Journal of Medical Toxicology. - 1556-9039. ; 19:4, s. 352-361
- Relaterad länk:
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http://dx.doi.org/10...
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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
- Introduction: Organophosphates (OPs) are a major public health problem worldwide due to ease of access and high toxicity lacking effective biomarkers and treatment. Cholinergic agents such as OPs and carbamates are responsible for many pesticide-related deaths. While the inhibition of AChE is thought to be the main mechanism of injury, there are other important pathways that contribute to the overall toxicity of OPs such as mitochondrial dysfunction. An existing gap in OP poisoning are biomarkers to gauge severity and prognosis. Cell-free DNA (cfDNA) are novel biomarkers that have gained increased attention as a sensitive biomarker of disease with novel use in acute poisoning. This study investigates alterations in cerebral mitochondrial function in a rodent model of chlorpyrifos poisoning with the use of cfDNA as a potential biomarker. Methods: Twenty rodents were divided into two groups: Control (n = 10) and Chlorpyrifos (n = 10). Chlorpyrifos was administered through the venous femoral line with a Harvard Apparatus 11 Elite Syringe pump (Holliston, MA, USA) at 2 mg/kg. Animals were randomized to receive chlorpyrifos versus the vehicle (10% DMSO) for 60 min which would realistically present an acute exposure with continued absorption. At the end of the exposure (60 min), isolated mitochondria were measured for mitochondrial respiration along with measures of acetylcholinesterase activity, cfDNA, cytokines and western blot. Results: The Chlorpyrifos group showed a significant decrease in heart rate but no change in the blood pressure. There was a significant increase in bulk cfDNA concentrations and overall decrease in mitochondrial respiration from brain tissue obtained from animals in the Chlorpyrifos group when compared to the Control group with no difference in acetylcholinesterase activity. In addition, there was a significant increase in both IL-2 and IL-12 in the Chlorpyrifos group. Conclusions: In our study, we found that the total cfDNA concentration may serve as a more accurate biomarker of OP exposure compared to acetylcholinesterase activity. In addition, there was an overall decrease in cerebral mitochondrial function in the Chlorpyrifos group when compared to the Control group.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- Basic science
- Biomarker
- Chlorpyrifos
- Mitochondria
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Kao, Shih Han
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Shofer, Frances ...
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Greenwood, John ...
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Alomaja, Oladunn ...
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Ranganathan, Abh ...
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Piel, Sarah
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Mesaros, Clement ...
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Shin, Samuel S.
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Ehinger, Johanne ...
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Kilbaugh, Todd J ...
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Jang, David H.
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