Ellagic Acid Alleviates Imidacloprid-Induced Thyroid Dysfunction via <i>PI3K/Akt/mTOR</i>-Mediated Autophagy
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 thera...
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MDPI AG
2025-04-01
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| author | Amina A. Farag Mahmoud Mostafa Reham M. Abdelfatah Alshimaa Ezzat ELdahshan Samar Fawzy Gad Shimaa K. Mohamed Mona K. Alawam Aya Aly Elzeer Nesma S. Ismail Sally Elsharkawey Haneen A. Al-Mazroua Hatun A. Alomar Wedad S. Sarawi Heba S. Youssef |
| author_facet | Amina A. Farag Mahmoud Mostafa Reham M. Abdelfatah Alshimaa Ezzat ELdahshan Samar Fawzy Gad Shimaa K. Mohamed Mona K. Alawam Aya Aly Elzeer Nesma S. Ismail Sally Elsharkawey Haneen A. Al-Mazroua Hatun A. Alomar Wedad S. Sarawi Heba S. Youssef |
| author_sort | Amina A. Farag |
| collection | DOAJ |
| description | 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 (<i>Bcl</i>, <i>BAX</i>), and autophagy pathway (<i>PI3K/Akt/mTOR</i>, <i>P53</i>, <i>Beclin-1</i>). Exposure to IMI resulted in impaired thyroid function, the upregulated gene expression of the <i>PI3K/Akt/mTOR</i> pathway, and downregulated <i>P53</i> 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 <i>PI3K/Akt/mTOR</i>-mediated autophagy. |
| format | Article |
| id | doaj-art-79fb31241cdc477eb8b69fe73fa603d5 |
| institution | OA Journals |
| issn | 2305-6304 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-79fb31241cdc477eb8b69fe73fa603d52025-08-20T02:34:02ZengMDPI AGToxics2305-63042025-04-0113535510.3390/toxics13050355Ellagic Acid Alleviates Imidacloprid-Induced Thyroid Dysfunction via <i>PI3K/Akt/mTOR</i>-Mediated AutophagyAmina A. Farag0Mahmoud Mostafa1Reham M. Abdelfatah2Alshimaa Ezzat ELdahshan3Samar Fawzy Gad4Shimaa K. Mohamed5Mona K. Alawam6Aya Aly Elzeer7Nesma S. Ismail8Sally Elsharkawey9Haneen A. Al-Mazroua10Hatun A. Alomar11Wedad S. Sarawi12Heba S. Youssef13Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, EgyptDepartment of Pesticides, Faculty of Agriculture, Mansoura University, Mansoura 35516, EgyptDepartment of Histology, Faculty of Medicine, Benha University, Benha 13518, EgyptDepartment of Anatomy, Faculty of Medicine, Benha University, Benha 13518, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Cairo 11795, EgyptDepartment of Physiology, Faculty of Medicine, Benha University, Benha 13518, EgyptDepartment of Development of Animal Wealth, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, EgyptDepartment of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, EgyptDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Physiology, Faculty of Medicine, Benha University, Benha 13518, EgyptImidacloprid (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 (<i>Bcl</i>, <i>BAX</i>), and autophagy pathway (<i>PI3K/Akt/mTOR</i>, <i>P53</i>, <i>Beclin-1</i>). Exposure to IMI resulted in impaired thyroid function, the upregulated gene expression of the <i>PI3K/Akt/mTOR</i> pathway, and downregulated <i>P53</i> 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 <i>PI3K/Akt/mTOR</i>-mediated autophagy.https://www.mdpi.com/2305-6304/13/5/355thyroid dysfunctionellagic acidimidaclopridautophagynovasomesnetwork pharmacology |
| spellingShingle | Amina A. Farag Mahmoud Mostafa Reham M. Abdelfatah Alshimaa Ezzat ELdahshan Samar Fawzy Gad Shimaa K. Mohamed Mona K. Alawam Aya Aly Elzeer Nesma S. Ismail Sally Elsharkawey Haneen A. Al-Mazroua Hatun A. Alomar Wedad S. Sarawi Heba S. Youssef Ellagic Acid Alleviates Imidacloprid-Induced Thyroid Dysfunction via <i>PI3K/Akt/mTOR</i>-Mediated Autophagy Toxics thyroid dysfunction ellagic acid imidacloprid autophagy novasomes network pharmacology |
| title | Ellagic Acid Alleviates Imidacloprid-Induced Thyroid Dysfunction via <i>PI3K/Akt/mTOR</i>-Mediated Autophagy |
| title_full | Ellagic Acid Alleviates Imidacloprid-Induced Thyroid Dysfunction via <i>PI3K/Akt/mTOR</i>-Mediated Autophagy |
| title_fullStr | Ellagic Acid Alleviates Imidacloprid-Induced Thyroid Dysfunction via <i>PI3K/Akt/mTOR</i>-Mediated Autophagy |
| title_full_unstemmed | Ellagic Acid Alleviates Imidacloprid-Induced Thyroid Dysfunction via <i>PI3K/Akt/mTOR</i>-Mediated Autophagy |
| title_short | Ellagic Acid Alleviates Imidacloprid-Induced Thyroid Dysfunction via <i>PI3K/Akt/mTOR</i>-Mediated Autophagy |
| title_sort | ellagic acid alleviates imidacloprid induced thyroid dysfunction via i pi3k akt mtor i mediated autophagy |
| topic | thyroid dysfunction ellagic acid imidacloprid autophagy novasomes network pharmacology |
| url | https://www.mdpi.com/2305-6304/13/5/355 |
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