Linalool‐zinc oxide nanocomposite controls Toxoplasma gondii infection through inhibiting inflammation, oxidative stress, and pathogenicity

Abstract

The present in vitro and in vivo study aimed to fabricate and characterize linalool‐zinc oxide nanoparticles (Lin‐ZNP) and evaluate their effectiveness against Toxoplasma gondii infection in terms of inflammation, oxidative stress, and pathogenicity. Lin‐ZNP was synthesized using an ethanolic solution of polyvinyl alcohol. The anti‐Toxoplasma and cytotoxicity activities of Lin‐ZNP were investigated, along with its effects on nitric oxide (NO) production, caspase‐3 activity, and pro‐inflammatory genes. After treating T. gondii‐infected mice with Lin‐ZNP for 14 days, the number and size of tissue cysts, antioxidant potential, pro‐inflammatory cytokines, and T. gondii pathogenicity‐related genes were evaluated by real‐time polymerase chain reaction and Western blot analysis. The Lin‐ZNP composite showed a reduced tendency with an average size of 105 nm. Lin‐ZNP significantly reduced the viability of tachyzoites. The obtained selectivity index higher than 10, indicating high specificity for parasites with low cytotoxicity to normal cells. The Lin‐ZNP significantly (p < 0.05) increased the production of NO, caspase‐3 activity, and the expression levels of pro‐inflammatory genes. Lin‐ZNP significantly (p < 0.001) decreased the size and number of tissue cysts and caused a significant reduction in the level of malondialdehyde and a considerable increase (p < 0.001) in antioxidant enzymes and their expression genes. Lin‐ZNP significantly downregulated both mRNA and protein expression of the inflammation‐related markers associated with the TLRs/NF‐κB pathway. The expression levels of the T. gondii pathogenicity‐related genes were significantly downregulated (p < 0.05). The recent survey indicated that Lin‐ZNP manages T. gondii infection by its antioxidant activity and inhibiting the TLRs/NF‐κB pathway without toxicity in mice.