Exploring the CD3/CD56/TNF-α/Caspase3 pathway in pyrethroid-induced immune dysregulation: curcumin-loaded chitosan nanoparticle intervention

Nawal Alsubaie; Yasmina M Abd-Elhakim; Amany Abdel-Rahman Mohamed; Tarek Khamis; Mohamed M M Metwally; Nawal Helmi; Afnan M Alnajeebi; Badriyah S Alotaibi; Amirah Albaqami; Wedad Mawkili; Mai A Samak; Samar A Eissa

doi:10.3389/fphar.2025.1505432

Exploring the CD3/CD56/TNF-α/Caspase3 pathway in pyrethroid-induced immune dysregulation: curcumin-loaded chitosan nanoparticle intervention

Front Pharmacol. 2025 Feb 6:16:1505432. doi: 10.3389/fphar.2025.1505432. eCollection 2025.

Authors

Nawal Alsubaie¹, Yasmina M Abd-Elhakim², Amany Abdel-Rahman Mohamed², Tarek Khamis^{3

4}, Mohamed M M Metwally^{5

6}, Nawal Helmi⁷, Afnan M Alnajeebi⁷, Badriyah S Alotaibi⁸, Amirah Albaqami⁹, Wedad Mawkili¹⁰, Mai A Samak^{11

12}, Samar A Eissa¹³

Affiliations

¹ Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
² Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
³ Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁴ Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁵ Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, King Salman International University, Ras Sidr, Egypt.
⁶ Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁷ Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
⁸ Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
⁹ Department of Clinical Laboratory Sciences, Turabah University College, Taif University, Taif, Saudi Arabia.
¹⁰ Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
¹¹ Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
¹² College of Medicine, University of Ha'il, Ha'il, Saudi Arabia.
¹³ Department of Medical Microbiology and Immunology, Faculty of Medicine, Kafrelsheikh University, Kafr ElSheikh, Egypt.

Abstract

Introduction: Conflict reports exist on the impact of pyrethroid insecticides on immune function and the probable underlying mechanisms.

Methods: 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.

Results: 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.

Conclusion: 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: CD56; MDA; ROS; anemia; caspase-3; mRNA expression; proinflammatory cytokines; pyrethroids.