Pharmaceutical Research Center, Pharmaceutical Technology Institute, School of Pharmacy, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad, 9177948954, Iran.
Social Security Organization (SSO), Mashhad, Razavi Khorasan, Iran.
Sci Rep. 2022 Sep 16;12(1):15578. doi: 10.1038/s41598-022-20010-3.
Acute intoxication with diazinon (DZN) as a pesticide causes mortality and morbidity annually. This study shows the impact of sub-acute toxicity of DZN 20 mg/kg and the protective activities of chrysin (CH) as a flavone under the flavonoids family (12.5, 25 and 50 mg/kg) were assessed on BALB/c mouse immune system. The changes in morphological and functional properties of the immune system on thymus, spleen and liver histopathology, sub-populations of T lymphocytes, cytokines levels, transcription factors, complement function, phagocytosis, specific and total antibody productions were considered. The histopathological effects of DZN on the spleen and thymus were not significant, but the liver was damaged remarkably. In the presence of CH, the toxic effect of DZN is suppressed. DZN significantly decreased the number of whole blood TCD4, TCD8 and NK cells and suppressed the phagocytosis, delayed-type hypersensitivity (DTH) responses to sheep red blood cell (SRBC). Furthermore, it suppressed specific anti-SRBC-Ab, total IgG and IgM production, T-bet expression, and IFN-γ production. In contrast, DZN did not significantly affect complement function and the number of NK cells, TCD4 and TCD8 splenocytes. However, it potentiated the expression of GATA-3, ROR-γt and FOXP3 gene expression and consequently produced IL-4, IL-10, IL-17 and TGF-β in whole blood. CH not only significantly increased the variables mentioned above at 12.5, 25 and 50 mg/kg but also could overcome the toxic effects of DZN on whole blood lymphocyte sub-populations and specific and total Ab production in 25 and 50 mg/kg concentrations, phagocytosis and DTH responses in 50 mg/kg, and modulation of the transcription factors and cytokine production, mainly in 25 and 50 mg/kg. In conclusion, DZN in sub-acute doses could remarkably deteriorate immune responses. However, CH can overcome the toxic effects of DZN on the immune components and functions of the immune system.
急性敌敌畏(DZN)中毒作为一种杀虫剂,每年都会导致死亡和发病。本研究表明,敌敌畏 20mg/kg 的亚急性毒性以及黄酮类家族中白杨素(CH)的保护作用(12.5、25 和 50mg/kg)对 BALB/c 小鼠免疫系统的影响。考虑了胸腺、脾和肝组织病理学、T 淋巴细胞亚群、细胞因子水平、转录因子、补体功能、吞噬作用、特异性和总抗体产生的免疫系统形态和功能特性的变化。白杨素在存在时,敌敌畏的毒性作用受到抑制。DZN 对脾和胸腺的组织病理学影响不显著,但肝脏明显受损。DZN 显著降低了全血 TCD4、TCD8 和 NK 细胞的数量,并抑制了吞噬作用、迟发型超敏反应(DTH)对绵羊红细胞(SRBC)的反应。此外,它抑制了特异性抗 SRBC-Ab、总 IgG 和 IgM 的产生、T-bet 的表达和 IFN-γ 的产生。相比之下,DZN 对补体功能和 NK 细胞、TCD4 和 TCD8 脾细胞的数量没有显著影响。然而,它增强了 GATA-3、ROR-γt 和 FOXP3 基因表达,随后在全血中产生了 IL-4、IL-10、IL-17 和 TGF-β。白杨素不仅在 12.5、25 和 50mg/kg 时显著增加了上述变量,而且在 25 和 50mg/kg 时还能克服敌敌畏对全血淋巴细胞亚群和特异性及总 Ab 产生、50mg/kg 时的吞噬作用和 DTH 反应以及转录因子和细胞因子产生的毒性作用,主要在 25 和 50mg/kg 时。总之,亚急性敌敌畏剂量可显著恶化免疫反应。然而,CH 可以克服敌敌畏对免疫系统免疫成分和功能的毒性作用。