Danlu Tongdu Tablets: Safety evaluation and mechanism of hepatotoxicity in Sprague-Dawley rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE212036 | GEO | 2022/08/25
REPOSITORIES: GEO
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Project description:Male Sprague-Dawley rats [Crl:CD®(SD)IGS BR], weighing ~250 g at study initiation were obtained from Charles River Laboratories, Inc. (Wilmington, MA). Rats were housed singly in ventilated, stainless steel, wire-bottom hanging cages and fed non-certified Rodent Chow (Harlan Labs, Madison, WI) and water ad libitum and acclimated for at least 5 days after arrival. Rats were randomly assigned to various treatment groups (3 rats/group) and were dosed once daily by oral gavage with vehicle (0.2% hydroxypropylmethylcellulose at a dose volume of 10 ml/kg) or with 30, 100, or 200 mg/kg of A-998679. All rats were fasted overnight after their last dose, weighed and sacrificed under isoflurane anesthesia. Liver and small intestine (jejunum) were flash frozen in liquid nitrogen and stored at −80°C until processing for gene expression profiling on the Affymetrix platform.
2012-07-24 | GSE39525 | GEO
Project description:Male Sprague-Dawley rats [Crl:CD®(SD)IGS BR], weighing ~250 g at study initiation were obtained from Charles River Laboratories, Inc. (Wilmington, MA). Rats were housed singly in ventilated, stainless steel, wire-bottom hanging cages and fed non-certified Rodent Chow (Harlan Labs, Madison, WI) and water ad libitum and acclimated for at least 5 days after arrival. Rats were randomly assigned to various treatment groups (3 rats/group) and were dosed once daily by oral gavage with vehicle (0.2% hydroxypropylmethylcellulose at a dose volume of 10 ml/kg) or with 30, 100, or 200 mg/kg of A-998679. All rats were fasted overnight after their last dose, weighed and sacrificed under isoflurane anesthesia. Liver and small intestine (jejunum) were flash frozen in liquid nitrogen and stored at −80°C until processing for gene expression profiling on the Affymetrix platform.
2012-08-04 | GSE39850 | GEO
Project description:Male Sprague-Dawley rats [Crl:CD®(SD)IGS BR], weighing ~250 g at study initiation were obtained from Charles River Laboratories, Inc. (Wilmington, MA). Rats were housed singly in ventilated, stainless steel, wire-bottom hanging cages and fed non-certified Rodent Chow (Harlan Labs, Madison, WI) and water ad libitum and acclimated for at least 5 days after arrival. Rats were randomly assigned to various treatment groups (3 rats/group) and were dosed once daily by oral gavage with vehicle (0.2% hydroxypropylmethylcellulose at a dose volume of 10 ml/kg) or with 30, 100, or 200 mg/kg of A-998679. All rats were fasted overnight after their last dose, weighed and sacrificed under isoflurane anesthesia. Liver and small intestine (jejunum) were flash frozen in liquid nitrogen and stored at −80°C until processing for gene expression profiling on the Affymetrix platform. total of 11 samples, 3 biological replicates (rats) from each of 3 treatments groups 1. vehicle control 2. 30mg/kg A-998679 3. 100mg/kg A-998679 and 2 biological replicates from treatment group 4. 200mg/kg A-998679
2012-08-03 | E-GEOD-39850 | biostudies-arrayexpress
Project description:Male Sprague-Dawley rats [Crl:CD®(SD)IGS BR], weighing ~250 g at study initiation were obtained from Charles River Laboratories, Inc. (Wilmington, MA). Rats were housed singly in ventilated, stainless steel, wire-bottom hanging cages and fed non-certified Rodent Chow (Harlan Labs, Madison, WI) and water ad libitum and acclimated for at least 5 days after arrival. Rats were randomly assigned to various treatment groups (3 rats/group) and were dosed once daily by oral gavage with vehicle (0.2% hydroxypropylmethylcellulose at a dose volume of 10 ml/kg) or with 30, 100, or 200 mg/kg of A-998679. All rats were fasted overnight after their last dose, weighed and sacrificed under isoflurane anesthesia. Liver and small intestine (jejunum) were flash frozen in liquid nitrogen and stored at −80°C until processing for gene expression profiling on the Affymetrix platform. total of 12 samples, 3 biological replicates (rats) from each of 4 treatments groups 1. vehicle control 2. 30mg/kg A-988679 3. 100mg/kg A-998679 4. 200mg/kg A-998679
2012-07-23 | E-GEOD-39525 | biostudies-arrayexpress
Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of 4-methylcyclohexylmethanol in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments. A total of 58 samples were evaluated in this study. 29 were from liver and 29 were from kidney. Five biological replicate were obtained for the 0 mg/kg/day control group for both liver and kidney. All other non-zero dose groups contain 4 biological replicates. The control groups for liver and kidney are the 0 mg/kg dose groups for those organs.
2015-12-31 | E-GEOD-75657 | biostudies-arrayexpress
Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of crude 4-methylcyclohexylmethanol in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments. A total of 44 samples were evaluated in this study. 27 were from liver and 17 were from kidney. Signficant batch effects were detected with a subset of samples and these were removed from the study prior to data analysis and are therefore not included in this GEO series. 3 (kidney) or 4 (liver) biological replicate were obtained for the 0 mg/kg/day control group for both liver and kidney. All other non-zero dose groups contain 2-4 biological replicates. The groups that contain only 2 or 3 replicates do so due to a number of samples not passing QC as byproduct of batch effects. The control groups for liver and kidney are the 0 mg/kg dose groups for those organs.
2015-12-31 | E-GEOD-75655 | biostudies-arrayexpress
Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of crude 4-methylcyclohexylmethanol in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments.
2015-12-31 | GSE75655 | GEO
Project description:High levels of hepcidin, the main regulator of systemic iron metabolism leads to various diseases. Targeting hepcidin and lowering its concentration is a possible form of intervention in order to treat these diseases. High turnover rate of hepcidin is a major drawback of therapies directly targeting this peptide. We developed two monoclonal antibodies (mAbs) ABT-207 and h5F9-AM8 which inhibit hemojuvelin also known as repulsive guidance molecule c (RGMc) and downregulate hepcidin. After a single application of these antibodies hepcidin expression in liver and its concentration in serum were reduced. Serum iron increased for several weeks. The RGMc antibodies show a pronounced dose response relationship in rats with h5F9-AM8 having an IC50 (UIBC) of ~80 fold higher than ABT-207. When hepcidin levels were downregulated iron deposition in the liver was visible histologically one week post application. The anitbody-mediated iron deposition was not associated with any toxicologically relevant effect at the doses and timepoints evaluate. Iron depositions seen after 14 weekly treatments with ABT-207 were partially reversible in rats and in cynomolgus monkeys. Due to their long-lasting effects and excellent safety profile, both RGMc-blocking antibodies ABT-207 and h5F9-AM8 are favorable clinical candidates for diseases characterized by high serum hepcidin levels like anemia of chronic disease. Female Sprague-Dawley rats [Crl:CD®(SD)IGS BR], weighing ~200 g at study initiation were obtained from Charles River Laboratories, Inc. Rats were housed singly in ventilated, stainless steel, wire-bottom hanging cages, fed non-certified Rodent Chow and water ad libitum and acclimated for at least 5 days after arrival. Rats were randomly assigned to various treatment groups (5 rats/group) and were dosed once weekly by IV injection via tail vein with vehicle (30mM Histidine, 8% w/v Sucrose, pH6.0, + 0.02% Tween 80) or with 0.02, 0.2, or 20 mg/kg of RGMc antibody for a total of 4 doses. All rats were sacrificed under isoflurane anesthesia 24 hours after final dose. Liver and spleen waere flash frozen in liquid nitrogen and stored at 80°C until processing for gene expression profiling on the Affymetrix platform. total of 12 samples, 3 biological replicates (rats) from each of 4 treatments groups 1. vehicle control (30mM Histidine, 8% w/v Sucrose, pH6.0, + 0.02% Tween 80) 2. 0.02 mg/kg RGMC Ab 3. 0.2 mg/kg RGMC Ab 4. 20 mg/kg RGMC Ab; rats were dosed by IV injection via tail vein once weekly for 4 total doses, dose volume 2mL/kg/week
2014-11-14 | E-GEOD-63200 | biostudies-arrayexpress
Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of propylene glycol phenyl etherl in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments. A total of 49 samples were evaluated in this study. 25 were from liver and 24 were from kidney. Five biological replicate were obtained for the 0 mg/kg/day control group for both liver and kidney. All other non-zero dose groups contain 4 biological replicates. The control groups for liver and kidney are the 0 mg/kg dose groups for those organs.
2015-12-31 | E-GEOD-75656 | biostudies-arrayexpress
Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of 4-methylcyclohexylmethanol in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments.
2015-12-31 | GSE75657 | GEO