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Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
Published on: October 6, 2023
Paulownia tomentosa leaf extract mitigates lambda-cyhalothrin-induced thyroid dysfunction via modulation of
Samah A El-Hashash1, Ethar E Elkholy1, Asmaa M El-Gawish1
1Department of Nutrition and Food Science, Faculty of Home Economics, Al-Azhar University, Nawag, Tanta 31732, Egypt.
Abstract:
Pyrethroid pesticides are recognized endocrine disruptors that can disrupt hormonal homeostasis in vertebrates, particularly thyroid function. This study investigated whether an ethanolic extract of Paulownia tomentosa leaves (PLE) could alleviate lambda-cyhalothrin-induced (LCT) thyroid toxicity in mice. The phenolic profile of PLE was confirmed by HPLC, and cytotoxicity was assessed using the MTT assay, which identified 9 mg/kg body weight as a suitable dose. Twenty adult male mice were divided into four groups: control, PLE alone (9 mg/kg), LCT alone (2 mg/kg), and combined PLE+LCT treatment for 28 days. LCT exposure produced marked thyroid dysfunction, reflected by increased serum TSH and reduced T₃ and T₄, accompanied by elevated MDA and pro-inflammatory cytokines, reduced antioxidant enzyme activities, and intensified apoptotic responses. Gene expression analysis demonstrated significant downregulation of thyroid hormone synthesis genes (Slc5a5/NIS, Tpo, Tg) and antioxidant defense markers (Nfe2l2/Nrf2, Hmox1/HO-1), alongside pronounced upregulation of inflammatory genes (Tnf, Il1b) and pro-apoptotic mediators (Bax, Casp3), with suppression of Bcl2. Histological alterations included follicular degeneration, colloid depletion, and reduced follicle diameter. Co-administration of PLE substantially attenuated these biochemical, molecular, and structural alterations, restoring thyroid-related and antioxidant gene expression, reducing inflammatory and apoptotic markers, and partially normalizing follicular morphology. These protective effects likely relate to the phenolic constituents of PLE, which possess recognized antioxidant and anti-inflammatory activities. Overall, PLE demonstrates potential as a natural complementary agent against LCT-induced thyroid injury. Further studies are warranted to isolate the bioactive compounds and clarify their mechanisms.
Insights
Paulownia tomentosa leaf extract (PLE) protected mice from lambda-cyhalothrin (LCT)-induced thyroid toxicity. PLE mitigated endocrine disruption by reducing inflammation and oxidative stress, highlighting its potential as a natural thyroid protectant.
Area of Science:
- Endocrinology
- Toxicology
- Phytochemistry
Background:
- Pyrethroid pesticides, like lambda-cyhalothrin (LCT), are endocrine disruptors impacting vertebrate hormonal balance, especially thyroid function.
- Thyroid dysfunction can lead to significant health issues due to the critical role of thyroid hormones in metabolism and development.
Purpose of the Study:
- To investigate the protective effects of an ethanolic extract of Paulownia tomentosa leaves (PLE) against LCT-induced thyroid toxicity in a mouse model.
- To assess the impact of PLE on thyroid hormone levels, oxidative stress, inflammation, and apoptosis markers following LCT exposure.
Main Methods:
- HPLC analysis confirmed the phenolic profile of PLE; MTT assay determined a non-cytotoxic dose of 9 mg/kg.
- Adult male mice were divided into four groups: control, PLE alone, LCT alone, and combined PLE+LCT treatment for 28 days.
- Biochemical assays, gene expression analysis (RT-qPCR), and histological examination were performed to evaluate thyroid function and toxicity.
Main Results:
- LCT exposure induced significant thyroid dysfunction, characterized by altered TSH, T3, and T4 levels, increased oxidative stress (MDA), elevated pro-inflammatory cytokines, and heightened apoptosis.
- PLE co-administration significantly attenuated LCT-induced thyroid damage, restoring thyroid hormone levels, reducing oxidative stress and inflammation, and suppressing apoptotic pathways.
- PLE partially normalized histological alterations in the thyroid gland and modulated the expression of key genes involved in thyroid hormone synthesis, antioxidant defense, and inflammation.
Conclusions:
- Ethanolic extract of Paulownia tomentosa leaves exhibits significant protective effects against lambda-cyhalothrin-induced thyroid toxicity in mice.
- The observed protective mechanisms are likely attributed to the antioxidant and anti-inflammatory properties of PLE's phenolic constituents.
- PLE shows promise as a natural complementary agent for mitigating pesticide-induced endocrine disruption and thyroid injury.