Blood Gene Expression Profiling of an Early Acetaminophen Response
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ABSTRACT:
PROVIDER: PRJNA289528 | ENA |
REPOSITORIES: ENA
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Project description:Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.
2016-02-16 | GSE70786 | GEO
Project description:Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.
2016-02-16 | GSE70784 | GEO
Project description:Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. Overdosed patients admitted to the emergency room. Five male and female individuals from 19 - 59 years old were admitted to the emergency room following an overdose on acetaminophen. The patients presented 12hrs to 4 days after ingestion. ALT and AST elevated peaking beyond 400 U/I and 120 U/I. Blood was collected 2 or 5 days following ingestion.
2016-02-16 | E-GEOD-70786 | biostudies-arrayexpress
Project description:Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. Randomized, single-blind, placebo-controlled, clinical study. Healthy male and female individuals from 18 â 58 years old weighing 55 kg to 85 kg volunteered as subjects in the study. Subjects were enrolled for 14 days each and were acclimated for 3 days on a controlled, standardized whole-food diet in order to assure a uniform nutritional intake. Starting on day 0 and until day 7 relative to the start of dosing, each subject received daily repeat dosing every 6 hrs (i.e. 4x daily) of either 1g of acetaminophen or placebo pills orally. Blood was collected at 8 a.m. on each day of the clinical study for alanine aminotransferase (ALT) measurement and complete blood counts (CBC).
2016-02-16 | E-GEOD-70784 | biostudies-arrayexpress
Project description:Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4?g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24?h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.
| S-EPMC5782799 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series:; GSE5593: Acetaminophen (APAP) Rat Blood Training Gene Expression Data Set; GSE5594: Acetaminophen (APAP) Rat Blood Test Gene Expression Data Set; GSE5595: Acetaminophen (APAP) Rat Liver Test Gene Expression Data Set; The Supplementary files (appended below) contain the mapping for the decoding of blinded samples. Experiment Overall Design: Refer to individual Series
2008-06-14 | E-GEOD-5652 | biostudies-arrayexpress
Project description:The purpose of this study was to investigate whether expression of specific genes in peripheral blood can be used as surrogate marker(s) to detect and distinguish target organ-specific chemical toxicity in rats. Rats were intraperitoneally administered a single, acute dose of a well-established hepatotoxic (acetaminophen) or neurotoxic (methyl parathion) chemical. Administration of acetaminophen (AP) or methyl parathion (MP) in the rats resulted in hepatotoxicity as evidenced from elevated blood transaminase activities or neurotoxicity as evidenced from the inhibition of acetyl cholinesterase activity in the blood, respectively. Microarray analysis of the global gene expression profile of rat blood identified distinct gene expression markers capable of detecting and distinguishing hepatotoxicity and neurotoxicity induced by AP and MP, respectively. Differential expressions of the marker genes specific for hepatotoxicity and neurotoxicity were detectable in the blood much earlier than the appearance of the commonly used clinical markers, serum transaminases and acetyl cholinesterase. In summary, our results demonstrated that blood gene expression markers can detect and distinguish target organ toxicity non-invasively and with higher sensitivity than traditional surrogate markers. Keywords: blood, acetaminophen, methyl parathion, rat, hepatotoxicity, neurotoxicity
2009-06-01 | GSE13442 | GEO
Project description:Predose and postdose gene expression profiles of blood samples of five most susceptible and five most resistant rats to acetaminophen-induced hapatotoxicity were determined by microarray analysis. Four out of ten selected genes were found to be reproducibly in real-time PCR with independent set animals to predict the susceptible individuals to acetaminophen-induced hapatotoxicity. We combined gene expression profiles of predose and postdose rat blood to predict the susceptible individuals to acetaminophen-induced hapatotoxicity.
2015-09-07 | E-GEOD-68065 | biostudies-arrayexpress
Project description:The purpose of this study was to investigate whether expression of specific genes in peripheral blood can be used as surrogate marker(s) to detect and distinguish target organ-specific chemical toxicity in rats. Rats were intraperitoneally administered a single, acute dose of a well-established hepatotoxic (acetaminophen) or neurotoxic (methyl parathion) chemical. Administration of acetaminophen (AP) or methyl parathion (MP) in the rats resulted in hepatotoxicity as evidenced from elevated blood transaminase activities or neurotoxicity as evidenced from the inhibition of acetyl cholinesterase activity in the blood, respectively. Microarray analysis of the global gene expression profile of rat blood identified distinct gene expression markers capable of detecting and distinguishing hepatotoxicity and neurotoxicity induced by AP and MP, respectively. Differential expressions of the marker genes specific for hepatotoxicity and neurotoxicity were detectable in the blood much earlier than the appearance of the commonly used clinical markers, serum transaminases and acetyl cholinesterase. In summary, our results demonstrated that blood gene expression markers can detect and distinguish target organ toxicity non-invasively and with higher sensitivity than traditional surrogate markers. Keywords: blood, acetaminophen, methyl parathion, rat, hepatotoxicity, neurotoxicity 38 samples were analyzed in this experiment. 15 rats were intraperitoneally administered acetaminophen (AP), 15 rats were intraperitoneally administered methyl parathion (MP), and 8 rats were intraperitoneally administered vegetable oil. At time intervals of 4, 12, and 24 hours following administration of acetaminophen or methyl parathion, 4 rats per chemical were sacrificed and blood was collected. At the 168-hour time interval, 3 rats per chemical were sacrificed and blood was collected. The control animals were sacrificed at the 24-hour time interval. Therefore, there were four rats in each of the 4-, 12-, and 24-hour time points for each chemical and four control rats for each chemical. Similarly, there were three rats in the 168-hour time interval for each chemical. The groups for each chemical and time interval are labeled as follows: APâcontrolâ4 rats: blood_AP_0_4, blood_AP_0_5, blood_AP_0_33, and blood_AP_0_34 APâ4-hoursâ4 rats: blood_AP_4_35, blood_AP_4_38, blood_AP_4_39, and blood_AP_4_40 APâ12-hoursâ4 rats: blood_AP_12_41, blood_AP_12_42, blood_AP_12_43, and blood_AP_12_45 APâ24-hoursâ4 rats: blood_AP_24_47, blood_AP_24_48, blood_AP_24_49, and blood_AP_24_51 APâ168-hoursâ3rats: blood_AP_168_53, blood_AP_168_54, and blood_AP_168_56 MPâcontrolâ4 rats: blood_MP_0_1, blood_MP_0_2, blood_MP_0_3, and blood_MP_0_ 31 MPâ4-hoursâ4 rats: blood_MP_4_11, blood_MP_4_12, blood_MP_4_13, and blood_MP_4_22 MPâ12-hoursâ4 rats: blood_MP_12_20, blood_MP_12_23, blood_MP_12_24, and blood_MP_12_25 MPâ24-hoursâ4 rats: blood_MP_24_6, blood_MP_24_7, blood_MP_24_9, and blood_MP_24_21 MPâ168-hoursâ3rats: blood_MP_168_26, blood_MP_168_27, and blood_MP_168_29
2010-04-08 | E-GEOD-13442 | biostudies-arrayexpress
Project description:Predose and postdose gene expression profiles of blood samples of five most susceptible and five most resistant rats to acetaminophen-induced hapatotoxicity were determined by microarray analysis. Four out of ten selected genes were found to be reproducibly in real-time PCR with independent set animals to predict the susceptible individuals to acetaminophen-induced hapatotoxicity.
2015-09-07 | GSE68065 | GEO