ORIGINAL RESEARCH article
Front. Toxicol.
Sec. Environmental Toxicology
Imidacloprid Exposure in Rats Induces Cardiac Inflammatory Response through Activating TLR4/NF-κB/NLRP3 and JAK/STAT Signaling Pathways: Focus on the Berberine-Loaded Nanoliposomes
Provisionally accepted
Layla Alkharashi1
Amina Farag2
Noha Mohsen Gamil3
Yasmen Mahran4
Amira M. Badr1*
Heba Bayoumi2
Mahmoud Mohamed5Awatif Binmughram6Aljawharah Alquhayz6Ghada BinOaeid6*Nervan Bayoumy7Eman Elwakeel2
Reem Atawia4,8- 1Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457,, Riyadh, Saudi Arabia
- 2Benha University Faculty of Medicine, Banha, Egypt
- 3Misr University for Science and Technology, 6th of October City, Egypt
- 4Ain Shams University Faculty of Pharmacy, Cairo, Egypt
- 5Minia University Faculty of Pharmacy, Minya, Egypt
- 6King Saud University, Riyadh, Saudi Arabia
- 7King Saud University College of Medicine, Riyadh, Saudi Arabia
- 8Southwestern Oklahoma State University College of Pharmacy, Weatherford, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The neonicotinoid insecticide, imidacloprid (IMI), is one of the widely used pesticides with well-documented serious health effects that are noticeable with long-term exposure. However, the long-term effects of IMI on cardiac tissues have not been fully elucidated. Herein, we investigated the mechanisms of IMI-induced cardiotoxicity. Additionally, we examined the potential protective effects of the natural alkaloid, berberine (BBR), against IMI-induced cardiotoxicity. Rats received IMI (45mg/kg/day, orally) for thirty days, alone or in combination with BBR-loaded liposomes (BBR-Lip) at a dose of 10 mg/kg, intraperitoneally. Cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), oxidative stress, inflammatory markers, and histopathological alterations were assessed. IMI caused significant cardiac damage as shown by increased levels of cTnI and CK-MB and histopathological insults examined by H and E and transmission electron microscope. These changes were accompanied by the induction of oxidative stress and inflammatory markers. Additionally, IMI inhibited the expression of Nrf2, a powerful regulator of cellular antioxidant defense and activated inflammatory pathways by inducing expressions of TLR-4, NF-κB, NLRP3-inflammasome and gasdermin. Moreover, IMI induced cardiac expressions of TGF-β, p-JAK, and p-STAT, which worsens the oxidative stress and inflammatory status. Co-administration of BBR-Lip attenuated the biochemical, histological and molecular dysregulation induced by IMI in cardiac tissues. Collectively, this study provides mechanistic insights into the cardiotoxic effects of IMI as well as the potential protective effects of BBR-Lip.
Keywords: cardiotoxicity, imidacloprid, Inflammasomes, JAK/STAT, Berberine
Received: 08 Sep 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Alkharashi, Farag, Gamil, Mahran, M. Badr, Bayoumi, Mohamed, Binmughram, Alquhayz, BinOaeid, Bayoumy, Elwakeel and Atawia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Amira M. Badr
Ghada BinOaeid
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.