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The Quantitative Alteration of TLR4 in Rat Spleen after Exposure to Acrylonitrile and Subsequent Detoxification by Sodium Thiosulfate

Author(s): X.J. LI, B. Li1*, J.S. Huang, J.M. Shi1, W. Fan1 and Y.L. Zhou
Department of Occupational Health, 1Central Laboratory, Jinshan Hospital, Fudan University, No. 1508, Longhang Road, Jinshan district, Shanghai, 201508, China

Correspondence Address:
Department of Occupational Health,Jinshan Hospital, Fudan University, No. 1508, Longhang Road, Jinshan district, Shanghai, 201508, China E-mail:

Acrylonitrile is a potent mutagen and carcinogen for hepatocytes. A role of toll-like receptor 4 in the immune toxicity of acrylonitrile has been suggested in many studies. The following study was designed to assess the quantitative alteration of toll-like receptor 4 under the influence of sodium thiosulfate which was used to antagonize acrylonitrile-induced immune toxicity in rats. 70 Sprague Dawley rats were divided into 7 groups. Rats of control group were gavaged with saline for 4 weeks. Rats of acrylonitrile groups were daily gavaged by acrylonitrile of different concentrations for 4 weeks, whereas all rats of sodium thiosulfate groups received gavage of acrylonitrile 10 mg/kg/d for 4 weeks and for the 4th w, meanwhile daily intraperitoneal injection of sodium thiosulfate of different concentrations was administered to detoxify acrylonitrile. All rats were anesthetized and serum levels of aspartate aminotransferase and alanine aminotransferase were measured to evaluate liver damage. Spleens of rats from different groups were dissected for histopathologic examination and immunohistochemistry of toll-like receptor 4 protein in spleen. Concentrations of interleukin-1β and tumor necrosis facor-α in blood samples were also analyzed. Acrylonitrile decreased body and spleen weight of the rats and increased the levels of serum aspartate aminotransferase and alanine aminotransferase. There were significant visible changes in spleen microstructure in rats treated with acrylonitrile alone when compared with control group. Moreover, it was proved in our study that acrylonitrile of 10 mg/kg could cause the most significant increase in the quantity of toll-like receptor 4 protein, when compared with both acrylonitrile (L) and acrylonitrile (H) group. The expression of toll-like receptor 4 protein of all acetonitrile groups was stronger than that of all sodium thoisulfate groups, which was in accordance with the inflammation caused by acrylonitrile with or without the influence from sodium thiosulfate. Among all sodium thiosulfate groups, toll-like receptor 4 expression of sodium thoisulfate (L) group was stronger than that of sodium thoisulfate (M) and sodium thoisulfate (H) group. Administration of sodium thiosulfate on the fourth week after first 3 w treatment with acrylonitrile alleviated acrylonitrile-induced morphological alterations in spleen, hepatic enzymatic indexes including serum aspartate aminotransferase and alanine aminotransferase, as well as the expression of toll-like receptor 4. Therefore, we suggested that sodium thiosulfate could antagonize the immune toxicity induced by acrylonitrile, which was reflected by quantitative change in expression of toll-like receptor 4 protein.

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