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Độc Tính Phát Triển của Fipronil và Rotenone Trên Hệ Thống Thử Nghiệm Tế Bào Thần Kinh Người In Vitro
Tóm tắt
Sự tiếp xúc với thuốc trừ sâu trong thai kỳ và giai đoạn sau sinh sớm có thể gây ra nhiều loại dị tật thần kinh. Tuy nhiên, cho đến nay mới có một số ít thuốc trừ sâu được công nhận là có độc tính thần kinh phát triển. Gần đây, việc phát hiện thuốc trừ sâu fipronil trong trứng gà đã gây ra sự lo ngại trong công chúng. Tình trạng của fipronil như một yếu tố có khả năng gây độc tính thần kinh phát triển vẫn đang gây tranh cãi. Trong khi một số nghiên cứu in vivo và in vitro gợi ý độc tính đặc hiệu, các nghiên cứu in vitro khác lại không thể xác nhận lo ngại này. Ở đây, chúng tôi đã thử nghiệm fipronil và sản phẩm chuyển hóa chính của nó, fipronil sulfone, ở nồng độ từ 1.98 đến 62.5 µM, cùng với độc tố thần kinh phát triển đã được thiết lập, rotenone (0.004–10 µM) trong môi trường in vitro trên dòng tế bào tiền thân thần kinh người NT2. Chúng tôi phát hiện rằng rotenone làm suy giảm cả ba đầu mối độc tính phát triển đã thử nghiệm, sự phát triển của nhánh tế bào, sự phân hóa thần kinh và sự di chuyển của tế bào tiền thân một cách phụ thuộc vào liều lượng và rõ ràng có thể phân biệt với độc tính tế bào chung trong khoảng nanomolar. Fipronil và fipronil sulfone cụ thể ức chế sự di chuyển tế bào và sự phân hóa thần kinh, nhưng không ức chế sự phát triển của nhánh tế bào trong khoảng micromolar. Inhibitor rho-kinase Y-27632 đã khôi phục lại sự ức chế di cư của cả ba hợp chất (EC50 từ 12 đến 50 µM). Chất chống oxi hóa, n-acetyl cysteine, có thể cải thiện các tác động ức chế của fipronil lên cả ba đầu mối đã thử nghiệm (EC 50 từ 84 đến 164 µM), cho thấy sự tham gia của stress oxy hóa. Fipronil sulfone có tác động mạnh hơn fipronil, xác nhận tầm quan trọng của việc thử nghiệm các sản phẩm chuyển hóa cùng với các thuốc trừ sâu gốc. Chúng tôi kết luận rằng fipronil và fipronil sulfone in vitro thể hiện độc tính thần kinh phát triển đặc hiệu trên các tế bào thần kinh đang phát triển của mô hình người.
Từ khóa
#Fipronil #Rotenone #độc tính thần kinh phát triển #tế bào tiền thân thần kinh #stress oxy hóaTài liệu tham khảo
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