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Biochemical effects of chloral hydrate on male rats following 7-day drinking water exposure

2000· article· en· W2006719058 on OpenAlexaff
Raymond Poon, B. Nadeau, I. Chu

Bibliographic record

VenueJournal of Applied Toxicology · 2000
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicDrug-Induced Hepatotoxicity and Protection
Canadian institutionsHealth Canada
Fundersnot available
KeywordsChloral hydrateEndocrinologyInternal medicineChemistryGlutathioneTriglycerideToxicityAldehyde dehydrogenaseBiochemistryCholesterolEnzymeBiologyPharmacologyMedicine

Abstract

fetched live from OpenAlex

The biochemical and toxicological effects of chloral hydrate were investigated. Four groups (n = 7 per group) of male Sprague-Dawley rats (161-170 g) were administered chloral hydrate in drinking water at concentrations of 20, 200 or 2000 ppm for 7 days. The control group received phosphate-buffered water only. There were no treatment-related changes in the body weight gains, relative weights of major organs or haematological parameters. Trichloroacetic acid was significantly (P < 0.05) elevated in the serum of high-dose animals (7.75 +/- 5.14 mg dl(-1), mean +/- SD). In the high-dose animals there was a 36% increase in protein level in the liver homogenates but not in the corresponding 9000 g supernatants. Concurrently, there was a threefold increase in the activity of the hepatic peroxisomal enzyme palmitoyl CoA oxidase (PCO). A prominent change was the dose-related suppression in hepatic aldehyde dehydrogenase (ALDH) activity observed in all treatment groups, with the decrease ranging from 15% at 20 ppm to 68% at 2000 ppm. There were no significant decreases in the activity of hepatic enzymes ethoxyresorufin O-deethylase (EROD), benzyloxyresorufin O-dealkylase (BROD) and UDP-glucuronosyl-transferase (UDPGT). In the high-dose group there was a 30% increase in hepatic glutathione-S transferase (GST) activity, accompanied by a 13% increase in glutathione (GSH). Significant effects on lipids were observed in the liver of the high-dose animals, with a 15% decrease in hepatic cholesterol and triglyceride levels. There were no treatment-related changes in serum chemistry parameters, including cholesterol and triglyceride levels. Although in vitro assays showed chloral hydrate to be an inhibitor of serum pseudocholinesterase activity, with a 50% inhibition concentration (ic(50)( of approximately 0.7 mM at 5 mM butyrylthiocholine, no decrease in serum pseudocholinesterase activity was found in the treated animals. It was concluded that the liver is the target organ for chloral hydrate, with suppression of ALDH as the most sensitive endpoint followed by alteration in the GSH level and GST activity. Changes observed in the high-dose animals, such as increased peroxisomal PCO activity in the liver and perturbation of lipid homeostasis in the liver and blood, were likely to be associated with trichloracetic acid, the major metabolite of chloral hydrate.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.023
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.036
GPT teacher head0.341
Teacher spread0.305 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations17
Published2000
Admission routes1
Has abstractyes

Explore more

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