# 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

## TL;DR

This study shows that the pesticide imidacloprid harms rat hearts by causing inflammation and oxidative stress, but berberine-loaded nanoliposomes may help protect against this damage.

## Contribution

The study reveals novel mechanisms of imidacloprid-induced cardiotoxicity and introduces berberine-loaded nanoliposomes as a potential protective treatment.

## Key findings

- Imidacloprid exposure increases cardiac damage markers and activates inflammatory pathways like TLR4/NF-κB/NLRP3 and JAK/STAT.
- Berberine-loaded nanoliposomes reduce oxidative stress and inflammation caused by imidacloprid in rat hearts.
- The study identifies Nrf2 inhibition and gasdermin expression as key factors in imidacloprid-induced cardiotoxicity.

## Abstract

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 (45 mg/kg/day, orally) for 30 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 microscopy. 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.

Research diagram illustrating an experimental setup with mice divided into four groups: Control, Ber-Lip (10 mg/kg), IMI (45 mg/kg), and Ber-Lip plus IMI. Tissue and serum are collected on day 31 for analysis, including CAT, GSH, MDA, SOD, TBRS, TNF-α, IL-6, Western blot, cTnI, and CK-MB tests. A timeline indicates 30 days. A pathway diagram shows TLR4 activation leading to responses in Nrf2 and NF-kB pathways, influencing ROS, apoptosis, inflammation, and pyroptosis. Statistical analysis is depicted with a bar graph comparing control and treatment groups.