Reverse triiodothyronine (rT3) attenuates ischemia-reperfusion injury

[helvella]

In this paper, reverse T3 (rT3) is classified as a deiodinase II (D2) inhibitor. Which represents an interesting viewpoint. Further, it is then proposed as an agent in itself.

I'd like to see further research which clarifies beyond doubt exactly what is happening but it is at least interesting.

Biochem Biophys Res Commun. 2018 Nov 30;506(3):597-603. doi: 10.1016/j.bbrc.2018.10.031. Epub 2018 Oct 23.

Reverse triiodothyronine (rT3) attenuates ischemia-reperfusion injury.

Rastogi L1, Godbole MM2, Sinha RA3, Pradhan S4.

Author information

1 Dept. of Zoology, BR Ambedkar University, Lucknow, India; Dept of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

2 Dept. of Molecular Medicine & Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; Dept of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. Electronic address: [e-mail].

3 Dept of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

4 Dept. of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Abstract

Hypothyroidism has been associated with better recovery from cerebral ischemia-reperfusion (IR) injury in humans. However, any therapeutic advantage of inducing hypothyroidism for mitigating IR injury without invoking the adverse effect of whole body hypothyroidism remains a challenge. We hypothesize that a deiodinase II (D2) inhibitor reverse triiodothyronine (rT3) may render brain specific hypometabolic state to ensue reduced damage during an acute phase of cerebral ischemia without affecting circulating thyroid hormone levels. Preclinical efficacy of rT3 as a neuroprotective agent was determined in rat model of middle cerebral artery occlusion (MCAO) induced cerebral IR and in oxygen glucose deprivation/reoxygenation (OGD/R) model in vitro. rT3 administration in rats significantly reduced neuronal injury markers, infarct size and neurological deficit upon ischemic insult. Similarly, rT3 increased cellular survival in primary cerebral neurons under OGD/R stress. Based on our results from both in vivo as well as in vitro models of ischemia reperfusion injury we propose rT3 as a novel therapeutic agent in reducing neuronal damage and improving stroke outcome.

Copyright © 2018 Elsevier Inc. All rights reserved.

KEYWORDS:

Cerebral ischemia; MCAO; Stroke; Thyroid hormone; rT3

PMID: 30366665

DOI: 10.1016/j.bbrc.2018.10.031

ncbi.nlm.nih.gov/pubmed/303...

Full paper behind paywall here:

sciencedirect.com/science/a...

Another interesting rT3 post:

healthunlocked.com/thyroidu...

[Jacs]

Thanks Helvella, both abstracts provide interesting insight to rT3 although clearly as you say more research is needed.

Its a shame that most of the doctors and endos we come into contact with don’t appear to know or be interested in anything more than their standard training

[helvella Administrator in reply to Jacs]

Medicine is such a huge subject area, it is probably inevitable that most don't get very involved. It also always looks like standard training is based on the Delia Smith approach - apparently infallible recipes handed down. When the Yorkshire pudding doesn't rise, or the Black Forest Gateau sinks and falls apart, the recipe does not equip the follower with the means to recognise and correct the issues.

I find the most depressing side is that we generally just have endocrinologists who also seem adrift in the thyroid arena and do not really have thyroidologists. Sure, there are a few who have rather focused on thyroid, but the chances of an individual patient getting from initial GP consultation to thyroid specialist are rather poor and, even when it happens, the delays can be utterly unacceptable.

[TSH110 in reply to helvella]

You’d think there were adequate numbers of people with thyroid disorders for specialism to be the norm and to be sent to a thyroidologist if you have a thyroid problem needing specialist care. Could restructuring the discipline be helpful to moving things forward I wonder?

[diogenes Remembering]

Here is a paper making something of the same point:

Endocrinology. 1987 Apr;120(4):1590-6.

Brain cortex reverse triiodothyronine (rT3) and triiodothyronine concentrations under steady state infusions of thyroxine and rT3.

Goumaz MO, Kaiser CA, Burger AG.

Abstract

T4 and reverse T3 (rT3) can inhibit 5'-deiodinase type II activity in rat brain cortex, pituitary, and brown adipose tissue, raising the possibility that T4 may act in vivo after conversion to rT3. The aim of this study was to measure in hypothyroid (Tx) rats the content of brain cortex rT3 during a constant 7-day infusion of either [125I]T4 alone, corresponding to 12 pmol T4/day X 100 g body weight (BW), or together with 400 pmol T4/day. [125I]T4, rT3, and T3 were extracted from brain cortex, pituitary, kidney, and liver with a combination of adsorption chromatography on Sephadex G-25, HPLC, and immunoprecipitation. [131I]T4, T3, or rT3 were used as internal standards. [125I]rT3 could be detected in brain cortex, liver, and kidney in Tx rats infused with [125I]T4 (12 pmol T4/day X 100 g BW) and in those infused with 400 pmol T4/day X 100 g BW. The highest rT3 concentrations were found in brain cortex, where it represented 6% to 10.5% of the local T4 concentration. During an infusion of 400 pmol T4/day X 100 g BW, brain cortex T3 concentration was 6 times higher in the brain cortex than in serum, and even exceeded that of T4. In Tx rats receiving [125I]T4 alone the brain cortex to serum T3 ratio was 3:1, but the total serum T3 concentration, measured by RIA, was much higher than that due to conversion [0.50 +/- (SE) 0.1 pmol/ml vs. 0.018 +/- 0.002 pmol T3/ml], indicating thyroidal secretion. The effect of the blood-brain barrier on rT3 was measured by infusing [125I]rT3 over 4 days. After killing, rT3 was isolated as above. Approximately 3% of serum rT3 was retrieved from the brain cortex, whereas during the T4 infusion 40-50% of serum rT3 was found demonstrating that brain cortex rT3 is locally produced.

PMID: 3830062 DOI: 10.1210/endo-120-4-1590