N‐acetylcysteine reduced the immunotoxicity effects induced in vitro by azoxystrobin and iprodione fungicides in mice

• Published in: Environmental toxicology 2021-04, Vol.36 (4), p.562-571
• Main Authors: Naasri, Sahar, Helali, Imen, Aouni, Majoub, Mastouri, Maha, Harizi, Hedi
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Acetylcysteine - pharmacology; Aminoimidazole Carboxamide - analogs & derivatives; Aminoimidazole Carboxamide - toxicity; Animals; Antioxidants; Azoxystrobin; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Survival - immunology; Cells, Cultured; Concanavalin A; Cytokines; Cytokines - biosynthesis; Defence mechanisms; Dose-Response Relationship, Drug; Environmental Pollutants - toxicity; Enzymatic activity; Enzyme activity; Enzymes; Fungicides; Fungicides, Industrial - toxicity; Hydantoins - toxicity; Immune response; Immune system; Immunity; Immunomodulation; Immunotoxicity; in vitro; Interferon; Interleukins; Iprodione; Lipopolysaccharides; Lymphocytes T; Macrophages; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - immunology; Male; Mice; Necrosis; Neoplasms; Nitric oxide; N‐acetylcysteine; Oxidative stress; Peritoneum; Pesticides; Proliferation; Pyrimidines - toxicity; Spleen - drug effects; Spleen - immunology; Splenocytes; Strobilurins - toxicity; Toxicity; Tumor necrosis factor-TNF; Tumor necrosis factor-α; γ-Interferon
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23061

Azoxystrobin (AZO) and Iprodione (IPR) fungicides are extensively used worldwide, and therefore, contaminate all environmental compartments. The toxicity and the mechanisms by which they affected immune cells are complex and remain unknown. This study investigated the impact of AZO and IPR on the in vitro function of mice peritoneal macrophages including lysosomal enzyme activity and tumor necrosis factor (TNF)α and nitric oxide (NO) production in response to lipopolysaccharide (LPS) stimulation, the proliferation of mice splenocytes stimulated by concanavalin (Con)A and LPS, and the production of the Th1cytokine interferon‐gamma (IFNγ) and the Th2 cytokine interleukin (IL)‐4 and IL‐10 by ConA‐activated splenocytes. This is the first report indicating that AZO and IPR fungicides dose‐dependently inhibited mice macrophage lysosomal enzyme activity and LPS‐stimulated production of TNFα and NO. Mitogen‐induced proliferation of mice splenocytes was also suppressed by AZO and IPR in a dose‐dependent manner. More pronounced impact was observed on ConA‐induced response. The production of IFNγ by ConA‐stimulated splenocytes was dose‐dependently inhibited; however, the production of IL‐4 and IL‐10 increased in the same conditions. These results suggested that AZO and IPR polarized Th1/Th2 cytokine balance towards Th2 response. Overall, marked immunosuppressive effects were observed for AZO. The immunomodulatory effects caused by AZO and IPR were partially reversed by the pharmacological antioxidant N‐acetylcysteine (NAC), suggesting that both fungicides exerted their actions through, at least in part, oxidative stress‐dependent mechanism. Collectively, our data showed that AZO and IPR fungicides exerted potent immunomodulatory effects in vitro with eventually strong consequences on immune response and immunologically based diseases.