Imidacloprid (IMI) is a widely used insecticide known for its high selectivity
toward insects. Ellagic acid (EA) is a plant-derived polyphenolic compound recognized for
its therapeutic potential and favorable safety profile in the treatment of various diseases.
This study aimed to evaluate the therapeutic effects of EA, formulated as novasomes (NOV),
against IMI-induced thyroid dysfunction and to investigate the underlying mechanisms.
Rats were divided into four equal groups: control, EA-NOV, IMI, and IMI + EA-NOV.
Thyroid function was assessed by measuring free triiodothyronine (T3), free thyroxine (T4),
and thyroid-stimulating hormone (TSH) levels. Thyroid tissues were examined to evaluate
histopathological alterations, as well as to assess the oxidative/antioxidant pathway (Nrf2,
SOD, TAC, MDA), inflammatory pathway (IL-1β, TNF-α, NF-κB), apoptotic pathway (Bcl,
BAX), and autophagy pathway (PI3K/Akt/mTOR, P53, Beclin-1). Exposure to IMI resulted
in impaired thyroid function, the upregulated gene expression of the PI3K/Akt/mTOR pathway,
and downregulated P53 expression. Additionally, immunohistochemical staining
revealed Beclin-1-mediated autophagy, alongside increased apoptosis, oxidative stress, and
elevated levels of inflammatory cytokines. Conversely, EA improved thyroid function and
ameliorated histopathological alterations by enhancing autophagy-inducing pathways.
Additionally, the alleviation of oxidative stress was evidenced by the increased immunohistochemical
staining of Nrf2, which promoted the synthesis and activity of antioxidant
enzymes and reduced apoptotic and inflammatory markers. This study proposes the use of
EA as a potential protective, naturally occurring phytoceutical against IMI-induced thyroid
dysfunction, primarily through the modulation of PI3K/Akt/mTOR-mediated autophagy |
