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This study aimed to evaluate the toxicological effects of oral intake of Zinc oxide nanoparticles (ZnO NPs) on the structure of thymus and spleen. Twenty-four young male Wistar albino rats were assigned into two groups: group I (control) and group II (ZnO NPs treated group).The thymus and spleen were analyzed biochemically, histopathologically and immunohistochemically. After ZnO NPs intake, hematologically, the total leucocytic count was significantly increased while the RBCs and platelets counts and Hb % were significantly decreased. Biochemically, a significant decrease in serum total antioxidant capacity and anti-inflammatory cytokines including interleukin 4 and 10 (IL-4 and IL-10) levels was noted. While a significant increase in splenic and thymic malondialdehyde (MDA) and DNA shearing, as well as the studied proinflammatory cytokines; IL-1β, tumor necrotic factor (TNF-α) and interferon (INF-γ) levels was detected. Notably, we noted upregulation of the immunomodulatory [CD3, CD11b, heme oxygenase (HO-1)] and the inflammatory [toll-like receptor 4 and 6 (TLR4 and TLR6)] genes. Histopathologically, degenerative changes were detected in thymus and spleen of ZnO NPs treated group. While the immunohistochemical analysis of the ZnO NPs treated group revealed a decrease in the number of cells expressed positive reactions of anti-PCNA and an increase in the number of cells expressed positive reaction of anti-p53 in the thymus and spleen. In conclusion, ZnO NPs induced obvious immunotoxicity in the thymus and spleen, where oxidative/inflammatory pathway may be the potential mechanism underlying this immunotoxicity. © 2017 IUBMB Life, 69(7):528-539, 2017.

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