Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy.
Acetaminophen is a widely prescribed drug used to relieve pain and fever; however, it is a leading cause of drug-induced liver injury and a burden on public healthcare. In this study, hepatotoxicity in mice post oral dosing of acetaminophen was investigated using liver and sera samples with Fourier...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3446881?pdf=render |
| _version_ | 1819045341833461760 |
|---|---|
| author | Rekha Gautam Bhagawat Chandrasekar Mukta Deobagkar-Lele Srabanti Rakshit Vinay Kumar B N Siva Umapathy Dipankar Nandi |
| author_facet | Rekha Gautam Bhagawat Chandrasekar Mukta Deobagkar-Lele Srabanti Rakshit Vinay Kumar B N Siva Umapathy Dipankar Nandi |
| author_sort | Rekha Gautam |
| collection | DOAJ |
| description | Acetaminophen is a widely prescribed drug used to relieve pain and fever; however, it is a leading cause of drug-induced liver injury and a burden on public healthcare. In this study, hepatotoxicity in mice post oral dosing of acetaminophen was investigated using liver and sera samples with Fourier Transform Infrared microspectroscopy. The infrared spectra of acetaminophen treated livers in BALB/c mice show decrease in glycogen, increase in amounts of cholesteryl esters and DNA respectively. Rescue experiments using L-methionine demonstrate that depletion in glycogen and increase in DNA are abrogated with pre-treatment, but not post-treatment, with L-methionine. This indicates that changes in glycogen and DNA are more sensitive to the rapid depletion of glutathione. Importantly, analysis of sera identified lowering of glycogen and increase in DNA and chlolesteryl esters earlier than increase in alanine aminotransferase, which is routinely used to diagnose liver damage. In addition, these changes are also observed in C57BL/6 and Nos2(-/-) mice. There is no difference in the kinetics of expression of these three molecules in both strains of mice, the extent of damage is similar and corroborated with ALT and histological analysis. Quantification of cytokines in sera showed increase upon APAP treatment. Although the levels of Tnfα and Ifnγ in sera are not significantly affected, Nos2(-/-) mice display lower Il6 but higher Il10 levels during this acute model of hepatotoxicity. Overall, this study reinforces the growing potential of Fourier Transform Infrared microspectroscopy as a fast, highly sensitive and label-free technique for non-invasive diagnosis of liver damage. The combination of Fourier Transform Infrared microspectroscopy and cytokine analysis is a powerful tool to identify multiple biomarkers, understand differential host responses and evaluate therapeutic regimens during liver damage and, possibly, other diseases. |
| first_indexed | 2024-12-21T10:27:02Z |
| format | Article |
| id | doaj.art-486f571d2e0443d6851fd08a90889055 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T10:27:02Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-486f571d2e0443d6851fd08a908890552022-12-21T19:07:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4552110.1371/journal.pone.0045521Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy.Rekha GautamBhagawat ChandrasekarMukta Deobagkar-LeleSrabanti RakshitVinay Kumar B NSiva UmapathyDipankar NandiAcetaminophen is a widely prescribed drug used to relieve pain and fever; however, it is a leading cause of drug-induced liver injury and a burden on public healthcare. In this study, hepatotoxicity in mice post oral dosing of acetaminophen was investigated using liver and sera samples with Fourier Transform Infrared microspectroscopy. The infrared spectra of acetaminophen treated livers in BALB/c mice show decrease in glycogen, increase in amounts of cholesteryl esters and DNA respectively. Rescue experiments using L-methionine demonstrate that depletion in glycogen and increase in DNA are abrogated with pre-treatment, but not post-treatment, with L-methionine. This indicates that changes in glycogen and DNA are more sensitive to the rapid depletion of glutathione. Importantly, analysis of sera identified lowering of glycogen and increase in DNA and chlolesteryl esters earlier than increase in alanine aminotransferase, which is routinely used to diagnose liver damage. In addition, these changes are also observed in C57BL/6 and Nos2(-/-) mice. There is no difference in the kinetics of expression of these three molecules in both strains of mice, the extent of damage is similar and corroborated with ALT and histological analysis. Quantification of cytokines in sera showed increase upon APAP treatment. Although the levels of Tnfα and Ifnγ in sera are not significantly affected, Nos2(-/-) mice display lower Il6 but higher Il10 levels during this acute model of hepatotoxicity. Overall, this study reinforces the growing potential of Fourier Transform Infrared microspectroscopy as a fast, highly sensitive and label-free technique for non-invasive diagnosis of liver damage. The combination of Fourier Transform Infrared microspectroscopy and cytokine analysis is a powerful tool to identify multiple biomarkers, understand differential host responses and evaluate therapeutic regimens during liver damage and, possibly, other diseases.http://europepmc.org/articles/PMC3446881?pdf=render |
| spellingShingle | Rekha Gautam Bhagawat Chandrasekar Mukta Deobagkar-Lele Srabanti Rakshit Vinay Kumar B N Siva Umapathy Dipankar Nandi Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy. PLoS ONE |
| title | Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy. |
| title_full | Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy. |
| title_fullStr | Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy. |
| title_full_unstemmed | Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy. |
| title_short | Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy. |
| title_sort | identification of early biomarkers during acetaminophen induced hepatotoxicity by fourier transform infrared microspectroscopy |
| url | http://europepmc.org/articles/PMC3446881?pdf=render |
| work_keys_str_mv | AT rekhagautam identificationofearlybiomarkersduringacetaminopheninducedhepatotoxicitybyfouriertransforminfraredmicrospectroscopy AT bhagawatchandrasekar identificationofearlybiomarkersduringacetaminopheninducedhepatotoxicitybyfouriertransforminfraredmicrospectroscopy AT muktadeobagkarlele identificationofearlybiomarkersduringacetaminopheninducedhepatotoxicitybyfouriertransforminfraredmicrospectroscopy AT srabantirakshit identificationofearlybiomarkersduringacetaminopheninducedhepatotoxicitybyfouriertransforminfraredmicrospectroscopy AT vinaykumarbn identificationofearlybiomarkersduringacetaminopheninducedhepatotoxicitybyfouriertransforminfraredmicrospectroscopy AT sivaumapathy identificationofearlybiomarkersduringacetaminopheninducedhepatotoxicitybyfouriertransforminfraredmicrospectroscopy AT dipankarnandi identificationofearlybiomarkersduringacetaminopheninducedhepatotoxicitybyfouriertransforminfraredmicrospectroscopy |