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

IntroductionConflict reports exist on the impact of pyrethroid insecticides on immune function and the probable underlying mechanisms.MethodsThis study evaluated the effect of an extensively used pyrethroid insecticide, fenpropathrin (FTN) (15 mg/kg b.wt), on the innate and humoral immune components...

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Main Authors: 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1505432/full
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author Nawal Alsubaie
Yasmina M. Abd-Elhakim
Amany Abdel-Rahman Mohamed
Tarek Khamis
Tarek Khamis
Mohamed M. M. Metwally
Mohamed M. M. Metwally
Nawal Helmi
Afnan M. Alnajeebi
Badriyah S. Alotaibi
Amirah Albaqami
Wedad Mawkili
Mai A. Samak
Mai A. Samak
Samar A. Eissa
author_facet Nawal Alsubaie
Yasmina M. Abd-Elhakim
Amany Abdel-Rahman Mohamed
Tarek Khamis
Tarek Khamis
Mohamed M. M. Metwally
Mohamed M. M. Metwally
Nawal Helmi
Afnan M. Alnajeebi
Badriyah S. Alotaibi
Amirah Albaqami
Wedad Mawkili
Mai A. Samak
Mai A. Samak
Samar A. Eissa
author_sort Nawal Alsubaie
collection DOAJ
description IntroductionConflict reports exist on the impact of pyrethroid insecticides on immune function and the probable underlying mechanisms.MethodsThis 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.ResultsFTN 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.ConclusionThe 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.
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spelling doaj-art-fbf7b4c5089b4b4ea2ffaadb22e842322025-02-06T11:44:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-02-011610.3389/fphar.2025.15054321505432Exploring the CD3/CD56/TNF-α/Caspase3 pathway in pyrethroid-induced immune dysregulation: curcumin-loaded chitosan nanoparticle interventionNawal Alsubaie0Yasmina M. Abd-Elhakim1Amany Abdel-Rahman Mohamed2Tarek Khamis3Tarek Khamis4Mohamed M. M. Metwally5Mohamed M. M. Metwally6Nawal Helmi7Afnan M. Alnajeebi8Badriyah S. Alotaibi9Amirah Albaqami10Wedad Mawkili11Mai A. Samak12Mai A. Samak13Samar A. Eissa14Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaDepartment of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptDepartment of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptDepartment of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptLaboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptDepartment of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, King Salman International University, Ras Sidr, EgyptDepartment of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptDepartment of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi ArabiaDepartment of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, Turabah University College, Taif University, Taif, Saudi Arabia0Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan, Saudi Arabia1Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt2College of Medicine, University of Ha’il, Ha’il, Saudi Arabia3Department of Medical Microbiology and Immunology, Faculty of Medicine, Kafrelsheikh University, Kafr ElSheikh, EgyptIntroductionConflict reports exist on the impact of pyrethroid insecticides on immune function and the probable underlying mechanisms.MethodsThis 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.ResultsFTN 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.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1505432/fullpyrethroidsproinflammatory cytokinesCD56caspase-3mRNA expressionanemia
spellingShingle Nawal Alsubaie
Yasmina M. Abd-Elhakim
Amany Abdel-Rahman Mohamed
Tarek Khamis
Tarek Khamis
Mohamed M. M. Metwally
Mohamed M. M. Metwally
Nawal Helmi
Afnan M. Alnajeebi
Badriyah S. Alotaibi
Amirah Albaqami
Wedad Mawkili
Mai A. Samak
Mai A. Samak
Samar A. Eissa
Exploring the CD3/CD56/TNF-α/Caspase3 pathway in pyrethroid-induced immune dysregulation: curcumin-loaded chitosan nanoparticle intervention
Frontiers in Pharmacology
pyrethroids
proinflammatory cytokines
CD56
caspase-3
mRNA expression
anemia
title Exploring the CD3/CD56/TNF-α/Caspase3 pathway in pyrethroid-induced immune dysregulation: curcumin-loaded chitosan nanoparticle intervention
title_full Exploring the CD3/CD56/TNF-α/Caspase3 pathway in pyrethroid-induced immune dysregulation: curcumin-loaded chitosan nanoparticle intervention
title_fullStr Exploring the CD3/CD56/TNF-α/Caspase3 pathway in pyrethroid-induced immune dysregulation: curcumin-loaded chitosan nanoparticle intervention
title_full_unstemmed Exploring the CD3/CD56/TNF-α/Caspase3 pathway in pyrethroid-induced immune dysregulation: curcumin-loaded chitosan nanoparticle intervention
title_short Exploring the CD3/CD56/TNF-α/Caspase3 pathway in pyrethroid-induced immune dysregulation: curcumin-loaded chitosan nanoparticle intervention
title_sort exploring the cd3 cd56 tnf α caspase3 pathway in pyrethroid induced immune dysregulation curcumin loaded chitosan nanoparticle intervention
topic pyrethroids
proinflammatory cytokines
CD56
caspase-3
mRNA expression
anemia
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1505432/full
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