Mechanistic analysis of metabolomics patterns in rat plasma during administration of direct thyroid hormone synthesis inhibitors or compound

[helvella]

This new paper reports investigations into exactly what thyroid-related effects various substances had - some of which are known to suppress thyroid function, others which affect the rate of clearance of thyroid hormones.

Two warnings:

The full paper is not available. A great pity as we only have the slightest glimpse of what it is about. Worth following the second link if you are interested.

This research was done by BASF or its subsidiaries so commercially sensitivities might have affected what has been reported and, indded, what they were looking for!

Toxicol Lett. 2013 Dec 23. pii: S0378-4274(13)01466-5. doi: 10.1016/j.toxlet.2013.12.010. [Epub ahead of print]

Mechanistic analysis of metabolomics patterns in rat plasma during administration of direct thyroid hormone synthesis inhibitors or compounds increasing thyroid hormone clearance.

Montoya GA, Strauss V, Fabian E, Kamp H, Mellert W, Walk T, Looser R, Herold M, Krennrich G, Peter E, van Ravenzwaay B.

Abstract

For identification of toxicological modes of action (MOAs) a database (MetaMap®Tox) was established containing plasma metabolome consisting of approximately 300 endogenous metabolites. Each five male and female Wistar rats per groups were treated with>500 reference compounds over a period of 28 days. More than 120 specific toxicity patterns of common metabolite changes associated with unique MOAs were established. To establish patterns predictive effects on the thyroid, animals have been treated with reference compounds directly acting on the thyroid hormone formation (such as methimazole, ethylenethiourea) as well as liver enzyme inducers leading to an increased excretion of thyroid hormones and therewith to a secondary response of the thyroid (such as aroclor 1254 and boscalid). Here we present the plasma metabolite changes which form the patterns for direct and indirect effects on the thyroid. It is possible to identify metabolites which are commonly regulated irrespective of an indirect or direct effect on the thyroid as well as groups of metabolites separating both MOAs. By putting the metabolite regulations in the context of affected pathways helps to identify thyroid hormone inhibiting MOAs even when the hormone levels are not consistently changed. E.g., direct thyroid hormone synthesis inhibitors affect some enzymes in the urea cycle, increase the ω-oxidation of fatty acids and decrease glutamate and oxoproline levels, whereas indirect thyroid hormone inhibiting compounds interact with the lipid mediated and liver metabolism.

Copyright © 2013. Published by Elsevier Ireland Ltd.

KEYWORDS:

Biomarker, Metabolomics, Mode of action, Pattern, Thyroid, Toxicity

PMID:

24370789

ncbi.nlm.nih.gov/pubmed/243...

A little more is visible here:

sciencedirect.com/science/a...

Rod

[Coastwalker]

Read it Helvella,

Understand some of it, but I need an 'Ology' in it to understand it all.

[helvella Administrator in reply to Coastwalker]

Certainly do! Wish I had one.

We keep seeing all sorts of odd things happening - and the patient reports are so widespread it is impossible to ignore them. But there is so very little that actually explains why things that affect thyroid hormone levels have the effects they do. Tends to be covered with dismissive statements like "thyroid hormone speeds up metabolism" or "lack of thyroid hormone slows down metabolism" - but how? And why? And why do these things affect only some people? And what could be done about them?

Rod

[Coastwalker in reply to helvella]

Agree Helvella,

If we were all built the same we'd be robots and they'd get the fix it manual out to screw us back together again, if anything dropped off.

Well slightly off topic, but could connect one day if we're lucky.

Read recently about a man who was determined to get rid of his diabetes.

He had to go on a certain 'few type foods' diet for 11 weeks, (might be making that one up though )

He kept to this bland diet, no sugar, or yummy foods etc., had lots of soups made from veg, kept it up for 11 days only, till he could take it no longer, so stopped. Found he'd managed to cure himself of Diabetes in just 11 days.

He'd reset himself so maybe one day, we could all reset our inner workings back to 'factory settings' again, if need be.

Just a nice thought

[silverfox7 in reply to Coastwalker]

Just like when you get your computer in a mess! It would be great wouldn't it or if you could send your body back to a date you were fine with! That would be the secret of eternal youth!

[Coastwalker in reply to silverfox7]

A wishful thought Silverfox, but never know what's round the next corner