Molecular Mechanisms of Reduced Nerve Toxicity by Titanium Dioxide Nanoparticles in the Phoxim-Exposed Brain of Bombyx mori

Bombyx mori (B. mori), silkworm, is one of the most important economic insects in the world, while phoxim, an organophosphorus (OP) pesticide, impact its economic benefits seriously. Phoxim exposure can damage the brain, fatbody, midgut and haemolymph of B. mori. However the metabolism of proteins and carbohydrates in phoxim-exposed B. mori can be improved by Titanium dioxide nanoparticles (TiO(2) NPs). In this study, we explored whether TiO(2) NPs treatment can reduce the phoxim-induced brain damage of the 5th larval instar of B. mori. We observed that TiO(2) NPs pretreatments significantly reduced the mortality of phoxim-exposed larva and relieved severe brain damage and oxidative stress under phoxim exposure in the brain. The treatments also relieved the phoxim-induced increases in the contents of acetylcholine (Ach), glutamate (Glu) and nitric oxide (NO) and the phoxim-induced decreases in the contents of norepinephrine (NE), Dopamine (DA), and 5-hydroxytryptamine (5-HT), and reduced the inhibition of acetylcholinesterase (AChE), Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and Ca(2+)/Mg(2+)-ATPase activities and the activation of total nitric oxide synthase (TNOS) in the brain. Furthermore, digital gene expression profile (DGE) analysis and real time quantitative PCR (qRT-PCR) assay revealed that TiO(2) NPs pretreatment inhibited the up-regulated expression of ace1, cytochrome c, caspase-9, caspase-3, Bm109 and down-regulated expression of BmIap caused by phoxim; these genes are involved in nerve conduction, oxidative stress and apoptosis. TiO(2) NPs pretreatment also inhibited the down-regulated expression of H(+) transporting ATP synthase and vacuolar ATP synthase under phoxim exposure, which are involved in ion transport and energy metabolism. These results indicate that TiO(2) NPs pretreatment reduced the phoxim-induced nerve toxicity in the brain of B. mori.