Study On Mouse Liver And Kidney Toxicity Induced By Different Sizes Of Nano Tungsten Trioxide And Protective Effect Of Melatonin

As a kind of novel transition metal oxides and semiconductor materials, nano tungsten trioxide (nano-WO3) has a great application prospects on environmental monitoring, biomedical industry, military and many other fields due to its attractive physicochemical properties such as gaschromics, electrochromism, gas sensitivity and photocatalysis. Concomitant with its wide application, the problems on security of nano-W03 have attracted more and more attentions of researchers. However, to the best of our knowledge, few researches on biological effect of nano-WO3 were conducted, and the comparations of toxicity of nano-WO3 with different sizes haven’t been reported. In this research, WO3 nanorods with two kinds of different sizes (WO3 nanorods-S, S represent WO3 nanorods of small size and WO3 nanorods-L, similarly L represent WO3 nanorods of large size) were respectively intraperitoneally injected into BALB/c mice to access and compare the toxicity damage to mice livers and kidneys, and further revealed the possible mechanism of toxicity of the two dimensions of WO3 nanorods. Simultaneously, melatonin, as a protective agent. was adopted to protect the damage of livers and kidneys, which provides a reference for WO3 nanorods selection of appropriate size and their secure applications of WO3 nanorods.In this study, after exposure to WO3 nanorods-S and WO3 nanorods-L respectively, the indexes including the changes of mice body weight, hepatic function(alanine aminotransferase, ALT; aspartate aminotransferase, AST), renal function (Urea nitrogen, BUN; Creatinine, Cr) were determined as well as pathology observations of livers and kidneys were conducted to evaluate the degree of liver and kidney damage in mice while the indexes of oxidative stress in liver and kidney tissues (reactive oxygen species, ROS; malonaldehyde, MDA; glutathione, GSH; superoxide dismutase, SOD and 8-hydroxy deoxyguanosine,8-OHdG), and inflammatory indexes (immunoglobulin IgE; nuclear factor-kappa B, NF-kB; tumor necrosis factor alpha, TNF-a; interferon gamma, IFN-γ and interleukin-4, IL-4)were detected to explore the possible mechanism of the toxicity of the two types of WO3 nanorods, and the causes of the difference of toxicity between WO3 nanorods-S and WO3 nanorods-L. In this study, melatonin as a protective agent was used to explore the protective effect on the damage of liver and kidney tissues and its protection mechanism.The results of this study revealed, with regard to WO3 nanorods-S, that the renal function indicators BUN and Cr increased significantly at the exposure dose of 5 mg/kg, The glomerular cells in the renal tissue pathological slice displayed slight edema, and renal tubule begun to narrow; mice bodyweight decreased significantly and liver function indicators ALT and AST、indexes of oxidative stress in liver and kidney tissues including ROS level、MDA and 8-OHdG content, as well as inflammatory indexes including IgE content in blood serum and the content of NF-κB、TNF-α、IFN-γ、IL-4 in liver tissues markedly rised while GSH content and SOD activity reduced significantly in mice livers and kidneys when the exposure dose exceeded 10 mg/kg with the increase of the exposure dose of WO3 nanorods-S. The pathological changes of mice livers showed that liver cell appeared edema, nuclear pyknosis or even disappeared, and some cells appeared vacuolar degeneration. And the glomerular cells in the renal tissue pathological slice displayed aggravated edema, and renal tubule narrowed or disappeared, and pathological changes is more obvious at the highest dose in both liver and kidney tissues. but As for WO3 nanorods-L, renal function indicators including BUN and Cr content markedly increased when the exposure dose exceeded 10 mg/kg. When the exposure dose of WO3 nanorods-L was 20mg/kg, mice bodyweight reduced notablely and hepatic function indicators including the level of ALT and AST、indexes of oxidative stress in liver and kidney tissues including ROS level、MDA and 8-OHdG content obviously rised, but GSH content and SOD activity reduced significantly in both mice livers and kidneys tissues, inflammatory level including IgE content in blood serum as well as NF-κB、 TNF-α、IFN-γ、IL-4 content in liver tissues also increased markedly. At the dose of 20mg/kg of WO3 nanorods-L, Similar pathological changes of mice livers and kidneys were observed perspectively, when compared with WO3 nanorods-S exposure group where explosure dose exceeded 10mg/kg, but the degree of pathology was no more obvious than nanorods-S exposure group of above 10mg/kg dose. By pretreating melatonin to the mice which was to be intraperitoneally injected 20mg/kg WO3 nanorods-L, the results revealed that, compared with mice merely exposured to 20mg/kg WO3 nanorods-L, mice body weight、the degree of hepatic and renal function damages relieved obviously and that the level of oxidative stress and inflammatory decreased significantly and also pathologic lesions of livers and kidneys alleviated to some extent.According to the results of the study, WO3 nanorods-S could cause mice liver and kidney toxic effect when the dose exceeded 5mg/kg, and WO3 nanorods-L result in obvious mice liver and kidney toxic effect when the dose were above 10mg/kg and 20mg/kg respectively. One of possible mechanism, which caused the damage of liver and kidney, was considered as oxidative stress and inflammation. Furthermore, the size effect of WO3 nanorods could be the reason why the toxic effect of WO3 nanorods-S was greater than WO3 nanorods-L. In this study,2.5mg/kg WO3 nanorods-S and 5mg/kg WO3 nanorods-L would be the safe dose for mice. Melatonin could protect mice liver and kidney tissues by reducing the damage degree of function of liver and kidney and lowing the level of oxidative stress and inflammation to alleviate the damage of mice liver and kidney tissues which were resulted from WO3 nanorods-L.