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Potential protective effects of chrysin against immunotoxicity induced by diazinon
Majid Zeinali1,2, Azam Shafaei3, Houshang Rafatpanah4
1Pharmaceutical Research Center, Pharmaceutical Technology Institute, School of Pharmacy, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad, 9177948954, Iran.
Abstract:
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.
Insights
Sub-acute diazinon (DZN) pesticide exposure damages the mouse immune system, particularly the liver. Chrysin (CH) supplementation protected against DZN toxicity, restoring immune functions and cell populations.
Area of Science:
- Immunology
- Toxicology
- Pharmacology
Background:
- Diazinon (DZN) is a widely used organophosphate pesticide with known acute toxicity.
- Sub-acute exposure to pesticides can lead to subtle but significant alterations in immune system function.
- Flavonoids, such as chrysin (CH), are plant-derived compounds with potential antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the immunotoxic effects of sub-acute diazinon (DZN) exposure in BALB/c mice.
- To evaluate the protective potential of chrysin (CH) against DZN-induced immunotoxicity.
- To assess the impact of DZN and CH on various immune parameters, including cellularity, cytokine profiles, and antibody production.
Main Methods:
- BALB/c mice were administered DZN (20 mg/kg) with or without varying doses of CH (12.5, 25, 50 mg/kg).
- Immune system components assessed included liver, spleen, and thymus histopathology, T lymphocyte sub-populations (TCD4+, TCD8+, NK cells), cytokine levels, transcription factors, complement function, phagocytosis, and antibody production.
- Key immune markers like T-bet, GATA-3, ROR-γt, FOXP3, IFN-γ, IL-4, IL-10, IL-17, and TGF-β were quantified.
Main Results:
- DZN caused significant liver damage and suppressed TCD4+, TCD8+, and NK cell counts in whole blood, phagocytosis, and antibody production (anti-SRBC-Ab, IgG, IgM).
- DZN also reduced T-bet expression and IFN-γ production, while increasing GATA-3, ROR-γt, FOXP3, IL-4, IL-10, IL-17, and TGF-β.
- Chrysin (CH) at 25 and 50 mg/kg effectively counteracted DZN's toxic effects on lymphocyte populations, antibody production, phagocytosis, and DTH responses, and modulated transcription factors and cytokine production.
Conclusions:
- Sub-acute DZN exposure significantly impairs immune responses in mice.
- Chrysin (CH) demonstrates significant protective effects against DZN-induced immunotoxicity.
- CH holds potential as a therapeutic agent to mitigate pesticide-induced immune system damage.
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