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

探索拟除虫菊酯诱导的免疫失调中的 CD3/CD56/TNF-α/Caspase3 通路:载姜黄素壳聚糖纳米粒子干预

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作者: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 Eissa3

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.

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.

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