Identification of Early Biomarkers during Acetaminophen-Induced Hepatotoxicity by Fourier Transform Infrared Microspectroscopy
Autor: | Bhagawat Chandrasekar, Srabanti Rakshit, Siva Umapathy, Mukta Deobagkar-Lele, Rekha Gautam, Dipankar Nandi, B N Vinay Kumar |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Mouse
medicine.medical_treatment Nitric Oxide Synthase Type II lcsh:Medicine Pharmacology Toxicology Biochemistry Mice chemistry.chemical_compound Methionine Drug Metabolism Spectroscopy Fourier Transform Infrared Pathology lcsh:Science Mice Knockout Liver injury Multidisciplinary Glycogen Liver Diseases Animal Models Interleukin 10 Cytokine Liver Medicine Cytokines Tumor necrosis factor alpha Cholesterol Esters Chemical and Drug Induced Liver Injury Inorganic & Physical Chemistry Research Article medicine.drug Drugs and Devices Immunology Gastroenterology and Hepatology Drug Absorption Model Organisms Diagnostic Medicine Chemical Biology medicine Animals Pharmacokinetics Biology Acetaminophen lcsh:R DNA Glutathione medicine.disease Mice Inbred C57BL Kinetics chemistry lcsh:Q Biomarkers General Pathology |
Zdroj: | PLoS ONE, Vol 7, Iss 9, p e45521 (2012) PLoS ONE |
ISSN: | 2381-3652 |
Popis: | 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/ 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 Tnf alpha and Ifn gamma 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. |
Databáze: | OpenAIRE |
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