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Comparative evaluation of rat and human in vitro assays for evaluation of thyroid toxicity.
ALTEX
December 2024
KaLy-Cell SAS, Plobsheim, France.
The effects of ten test chemicals towards thyroid sodium-iodide symporter (NIS), thyroid peroxidase (TPO), and deiodinases (DIOs) type I, II, and III were evaluated in in vitro rat and human systems and compared. Test chemicals known to directly affect TH levels in vivo were confirmed to effectively inhibit at least one of the tested in vitro endpoints, without significant disparities between species, and the tested compounds known to not affect thyroid function, were found ineffective. Interestingly, Iodide Transport Blocker 5, a potent non-competitive iodine uptake inhibitor, exhibited effects beyond direct NIS inhibition, by impacting NIS function through ATP depletion, and also inhibited TPO and DIO1/2 enzymes, although to a lesser extent.
View Article and Find Full Text PDFPharmacokinetic analysis of a phenobarbital overdose treated with urinary alkalinization alone.
Toxicol Rep
June 2024
Division of Medical Toxicology, Department of Emergency Medicine, UC San Diego Health, CA, USA.
Article Synopsis
- - Phenobarbital is a long-acting barbiturate used for treating alcohol withdrawal and epilepsy but can cause severe central nervous system depression in case of overdose.
- - A case study of a 14-year-old girl showed that urinary alkalinization with sodium bicarbonate was used successfully for treating phenobarbital overdose, enhancing drug elimination.
- - Despite the treatment increasing urinary excretion rates, there was no significant impact on the elimination half-life of the drug, indicating the need for further studies on the efficacy of urinary alkalinization in such cases.
Effects of pethoxamid treatment on the disposition of thyroxine in rats.
Toxicol Appl Pharmacol
June 2024
FMC Corporation, 2929 Walnut St, Philadelphia, PA, USA. Electronic address:
Article Synopsis
- - Pethoxamid (PXA) is a chloroacetamide herbicide that inhibits weed germination and has been found to cause thyroid follicular cell hyperplasia in high-dose male rats, but does not act as a genotoxic agent.
- - A study assessed the effects of PXA on the disposition of intravenously administered radioactive thyroxine in bile-duct cannulated rats, compared with a positive control (phenobarbital), showing increased liver weights and altered thyroid hormone clearance.
- - The findings suggest PXA affects thyroid hormone balance through increased T4 elimination in bile due to enzyme induction mechanisms, but these effects are likely not relevant to humans due to species-specific differences in thyroid hormone metabolism.
Mechanistic modelling of enzyme-restoration effects of new recombinant liver-targeted proteins in acute intermittent porphyria.
Br J Pharmacol
July 2022
Pharmacometrics & Systems Pharmacology, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain.
Background And Purpose: Acute intermittent porphyria (AIP) is a rare disease caused by a genetic mutation in the hepatic activity of the porphobilinogen-deaminase. We aimed to develop a mechanistic model of the enzymatic restoration effects of a novel therapy based on the administration of different formulations of recombinant human-PBGD (rhPBGD) linked to the ApoAI lipoprotein. This fusion protein circulates in blood, incorporating into HDL and penetrating hepatocytes.
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