Frequently utilized food additives contribute to immune system dysfunction, chronic inflammation and oxidative stress.

Extensive safety measures for food additives focus primarily on target organ toxicity, neglecting the potential effects on oxidative stress and inflammation-related disruptions in the immune system. This study evaluated the effects of four common food additives-monosodium glutamate (MSG), sodium nitrate (SN), sodium sulfite (SS), and butylated hydroxyanisole (BHA)-on splenic inflammation and oxidative stress markers in naïve female mice. The results showed that oral administration of MSG, SN, SS, and BHA-alone or in combination-for 4 weeks induced immune-suppressive effects and chronic antioxidative stress, via inflammatory responses in spleen. This was accompanied by overexpression of interferon-γ (IFN-γ), immunoglobulin G (IgG), tumor growth factor-β (TGF-β), catalase (CAT), and superoxide dismutase (SOD), and increased proportions of B regulatory (CD19+ CD24+) and T regulatory (CD4+ CD25+) cells, which may contribute to the downregulation of C-reactive protein (CRP), interleukin-1β (IL-1β), IL-6, IL-10, and malondialdehyde (MDA) in the spleen. Also, higher percentages of necrosis and late apoptosis in splenocytes were noted. In conclusion, exposure to dietary additives MSG, SN, SS, and BHA-alone or in combination-modulated markers of inflammation and oxidative stress and affected the expression of regulatory T and B cells, resulting in the immune system's dysfunctions. BHA showed the greatest negative impact, followed by MSG, with SS and SN having lesser effects. Because these additives are common in commercially packaged foods, they should be used sparingly, and more research is needed to understand their systemic and long-term toxic effects on different organs, particularly due to the rising use of new compounds at varying exposure levels.