Pro-inflammatory responses and oxidative stress induced by ZnO nanoparticles in vivo following intravenous injection

J. Fujihara, M. Tongu, H. Hashimoto, Y. Fujita, N. Nishimoto, T. Yasuda, H. Takeshita

Department of Legal Medicine, Shimane University Faculty of Medicine, Izumo, Japan. jfujihar@med.shimane-u.ac.jp

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• Pharmacology

OBJECTIVE: To determine the toxicological effect of ZnO nanoparticles (NPs), inflammatory responses, serum biological parameters and oxidative stress markers of Superoxide dismutase (SOD) were evaluated followed by intravenous treatment of ZnO NPs in mice.

MATERIALS AND METHODS: Inflammatory responses induced by a dose of 0.2 mg/kg ZnO NPs, followed by a single intravenous treatment were examined in mice. In addition, the serum biological parameters and oxidative stress markers were evaluated. Blood and spleen were collected following treatment. The mRNA transcript levels of inflammatory-related genes (TNF-α and IL1-β) were elevated in the spleen cells of mice treated with ZnO NPs at 12h.

RESULTS: The elevated levels of TNF-α and IL1-β in supernatants of spleen cell cultures of mice treated with ZnO NPs were also observed at 24h. The serum aspartate aminotransferase, glutamate pyruvate alanine aminotransferase, and lactate dehydrogenase levels significantly increased at 6h and 12h in ZnO NPs treated group, indicating liver cell injury and tissue damage. On the other hand, no elevation was observed in BUN and Cre, biochemical markers of kidney damage. SOD activities were significantly elevated at 24 h and 48 h.

CONCLUSIONS: This study shows the ZnO induced pro-inflammatory response in vivo, that this response may be related to oxidative stress, and to show hepatic damage at an early stage.

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