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Pentoxifylline Explores New Horizons In Treatment Of Hashimoto Thyroiditis

paymanz

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https://www.omicsonline.com/open-ac...o-thyroiditis-0974-8369-1000293.php?aid=70469

Abstract
Hashimoto Thyroiditis is an autoimmune disease and the most common cause of hypothyroidism in developed countries. As the disease initiates unusual thyroidal antigens are exposed to the immune system. The immune system sensitizes to those antigens and creates a cell mediated autoimmune response against thyroid gland. Inflammatory cells infiltrate within thyroid follicles and destruct the follicles by inflicting oxidative stress and inducing apoptosis. The inflammatory process also reduces sensitivity of thyrocytes to Thyroid Stimulating Hormone (TSH). As the disease progresses and the follicles degrade, fibrotic tissue replaces the follicles until the whole gland becomes fibrotic. Pentoxiflline could inhibit autoimmune destruction of thyrocytes, suppress cell mediated immune response against thyroid, decrease oxidative damage to thyrocytes, increase sensitivity of thyrocytes to TSH and hinder fibrotic degeneration of thyroid. Thereby PTX could cure HT and alleviate symptoms of hypothyroidism.

Conclusion
All clues together, PTX is an anti-inflammatory/anti-oxidant agent and it may reduce inflammation and aberrant apoptosis of thyroid epithelial cells. It may reduce exposure of intra cellular/follicular components to immune system and decrease infiltration of leukocytes within thyroid follicles. It may ameliorate decreased responsiveness of throcytes to TSH. PTX may accelerate regeneration of damaged thyrocytes as it suppresses IFN-γ and up-regulates production of IL-10 and it also inhibits fibrosis of the gland. All in all PTX may have curative effects on HT and may have the potential to become an alternative treatment. Evaluation of the issue with clinical researches and cohort large studies are necessarily needed to validate/invalidate the hypothesis.

PTX as a TSH sensitizer

It is also hypothesized that PTX could improve the effects of TSH on thyrocytes. Two main mechanisms are postulated. As previously mentioned, IFN-γ inhibits functional and morphological response of human thyrocytes to TSH [12,48]. As previously mentioned, PTX down-regulates expression of IFN-γ. Thereby it is hypothesized that PTX could reduce the resistance of thyrocytes to TSH. On the other hand, as it is well known, classical human TSH signal transduction pathway includes cAMP as a secondary messenger. As a non-selective phosphodiesterase inhibitor, Pentoxifylline increases the amount of intracellular cAMP [62]. The same as TSH, FSH signal transduction highly depends on amounts of intracellular cAMP and it is shown that PTX boosts and improves the effects of FSH on male germinal cells [20]. As PTX increases the sensitivity to FSH, considering the issue that TSH and FSH are structurally similar to each other, it is hypothesized that PTX may do the same about TSH and thyrocytes. Indeed, it is hypothesized that PTX could ameliorate attenuated effects of TSH on thyrocytes, during HT.

It is also hypothesized that PTX increases sensitivity of thyrocytes to TSH and accelerates regeneration of damaged gland. Finally PTX could decelerate rate of fibrosis of the thyroid which is the final fate of the gland in HT

As previously mentioned, IFN-γ inhibits functional and morphological response of human thyrocytes to TSH [12,48]. Thus it is hypothesized that by down-regulating this cytokine, PTX could also increase sensitivity of thyrocytes to TSH and it could facilitate regeneration and redevelopment of thyroid tissue in response to TSH.
 
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