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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1505432
This article is part of the Research Topic Immune Response Modulation by Nanoparticle Formulations View all 4 articles

Exploring the CD3/CD56/TNF-α/Caspase3 Pathway in Pyrethroid-Induced Immune Dysregulation: Curcumin-Loaded Chitosan Nanoparticle Intervention

Provisionally accepted
Nawal Alsubaie Nawal Alsubaie 1*Yasmina Mohammed Abd-Elhakim Yasmina Mohammed Abd-Elhakim 2*Amany Abdel-Rahman Mohamed Amany Abdel-Rahman Mohamed 2Tarek Khamis Tarek Khamis 2Mohamed Metwally Mohamed Metwally 3Nawal Helmi Nawal Helmi 4Afnan Alnajeebi Afnan Alnajeebi 4Badriyah Alotaibi Badriyah Alotaibi 1Amirah Albaqami Amirah Albaqami 5Wedad Mawkili Wedad Mawkili 6Mai A. Samak Mai A. Samak 7Samar A. Eissa Samar A. Eissa 8
  • 1 Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
  • 2 College of Veterinary Medicine, Zagazig University, Zagazig, Egypt
  • 3 King Salman International University, South Sinai, Egypt
  • 4 College of Science, Jeddah University, Jeddah, Saudi Arabia
  • 5 Taif University, Ta'if, Saudi Arabia
  • 6 Jazan University, Jizan, Saudi Arabia
  • 7 Faculty of Medicine, Zagazig University, Zagazig, Al Sharqia, Egypt
  • 8 Kafrelsheikh University, Kafr el-Sheikh, Kafr el-Sheikh, Egypt

The final, formatted version of the article will be published soon.

    Conflict reports exist on the impact of pyrethroid insecticides on immune function and the probable underlying mechanisms. Thus, this study evaluated the effect of an extensively used pyrethroid insecticide, fenpropathrin (FTN) (15 mg/kg b.wt), on the innate and humoral immune components, blood cells, splenic oxidative status, and mRNA expression of CD3, CD20, CD56, CD8, CD4, IL-6, TNF-α, and Caspase3 in a 60-day trial in rats. Besides, the possible defensive effect of curcumin-loaded chitosan nanoparticle (CML-CNP) (50 mg/kg b.wt) was evaluated. The results shown that FTN exposure resulted in hypochromic normocytic anemia, thrombocytosis, leukocytosis, and lymphopenia. Besides, a significant reduction in IgG, not IgM, but increased C3 serum levels was evident in the FTN-exposed rats. Moreover, their splenic tissues displayed a substantial increase in the ROS, MDA, IL-6, and IL-1β content, altered splenic histology, and reduced GPX, GSH, and GSH/GSSG. Furthermore, a substantial upregulation of mRNA expression of splenic CD20, CD56, CD8, CD4, CD3, IL-6, and TNF-α, but downregulation of CD8 was detected in FTN-exposed rats. FTN exposure significantly upregulated splenic Caspase-3 and increased its immunohistochemical expression, along with elevated TNF-α immunoexpression. However, the alterations in immune function, splenic antioxidant status, blood cell populations, and immune-related gene expression were notably restored in the FTN+CML-CNP-treated group. The findings of this study highlighted the immunosuppressive effects of FTN and suggested the involvement of many CD cell markers as a potential underlying mechanism. Additionally, the results demonstrated the effectiveness of CML-CNP in mitigating pollutant-induced immune disorders.

    Keywords: pyrethroids, proinflammatory cytokines, CD56, caspase-3, mRNA expression, Anemia, ROS, MDA

    Received: 02 Oct 2024; Accepted: 09 Jan 2025.

    Copyright: © 2025 Alsubaie, Abd-Elhakim, Mohamed, Khamis, Metwally, Helmi, Alnajeebi, Alotaibi, Albaqami, Mawkili, Samak and Eissa. 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:
    Nawal Alsubaie, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
    Yasmina Mohammed Abd-Elhakim, College of Veterinary Medicine, Zagazig University, Zagazig, Egypt

    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.