Paulownia tomentosa leaf extract mitigates lambda-cyhalothrin-induced thyroid dysfunction via modulation of Nrf2/HO-1, NF-κB, and Bax/Bcl-2 signaling pathways in mice.

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.