RESUMO
8:2 Fluorotelomer alcohol (8:2 FTOH) is widely used in houseware and industrial goods and is ubiquitous in the surrounding environment. 8:2 FTOH has been linked to hepatoxicity, nephrotoxicity, and reproductive toxicity, as well as endocrine-disrupting effects. However, as of yet, the research regarding immunotoxicity of 8:2 FTOH remains largely limited. In the present study, adult male C57BL/6 mice were administered with 10, 30, and 100 mg/kg/d 8:2 FTOH by gavage for 28 days to investigate its immunotoxicity in vivo. The results showed that exposure to 8:2 FTOH caused increases in liver weight and histological changes in the liver, including vacuolation, cell swelling, immune cell infiltration, karyopyknosis and nuclear swelling. No histological change in either the spleen or the thymus was observed after administration of 8:2 FTOH. In addition, exposure to 8:2 FTOH reduced the concentration of IL-1ß in serum, and mRNA levels of IL-1ß, IL-6, and TNF-α in both the thymus and spleen. CXCL-1 mRNA expression was downregulated in both the liver and thymus after 8:2 FTOH administration, while only IL-1ß mRNA expression was upregulated in the liver. Moreover, the exposure of primary cultured splenocytes to 8:2 FTOH inhibited the ConA-stimulated proliferation of splenocytes at concentrations of 30 and 100 µM, and the LPS-stimulated proliferation of splenocytes at 100 µM. Furthermore, 8:2 FTOH inhibited the level of secreted IFN-γ in ConA-stimulated splenocytes. The results obtained in the study demonstrated that 8:2 FTOH posed potential immunotoxicity and liver injury in mice. Our findings will provide novel data for the health risk assessment of 8:2 FTOH.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/imunologia , Poluentes Ambientais/toxicidade , Fluorocarbonos/toxicidade , Fígado/efeitos dos fármacos , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Concanavalina A/farmacologia , Citocinas/sangue , Citocinas/genética , Relação Dose-Resposta a Droga , Fígado/imunologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Baço/efeitos dos fármacos , Baço/imunologiaRESUMO
Short-chain chlorinated paraffins (SCCPs, C10-13) were listed as persistent organic pollutants (POPs) by the Stockholm Convention in 2017 and pose extensive exposure risks to humans. To our knowledge, there have been no studies reporting the immmunomodulatory effects of SCCPs until now. C9-CPs have also been shown to be present in the environment. In this study, adult male C57BL/6 mice were exposed to 1, 10, or 100â¯mg/kg/d C9-13-CPs by gavage for 28â¯d. The results showed that compared to those of the controls, exposure to C9-13-CPs led to increased spleen weight, delimited germinal centers, enhanced energy metabolism, and elevated glutathione content, but no variation in the malonaldehyde level in the spleen was observed. Exposure to C9-13-CPs also increased the populations of splenic lymphocytes, T lymphocytes, NK cells, and the ratio of the CD3+/CD19+ subsets and CD4+/CD8+ subsets compared to those of the controls. RNA-seq revealed 424 differentially expressed genes (DEGs) (fold changeâ¯≥â¯1.5, FDRâ¯<â¯0.05) in the spleen between the control group and the 100â¯mg/kg/d C9-13-CPs-treated group. KEGG analysis demonstrated that folate biosynthesis, pathways in cancer and thyroid hormone signaling were the three most significantly enriched pathways, and despite not reaching statistical significance, some immune-related pathways were also enriched in the KEGG functional enrichment analysis, including the chemokine signaling pathway (FDRâ¯<â¯0.0584), the NF-κB signaling pathway (FDRâ¯<â¯0.0663), Th17 cell differentiation (FDRâ¯<â¯0.0839), and the Jak-STAT signaling pathway. Moreover, compared to those of the controls, exposure to C9-13-CPs enhanced the Concanavalin A (Con A)-stimulated cultured splenocyte proliferation, while the exposure showed no effect on the splenocyte proliferation that was stimulated by lipopolysaccharides (LPS). Taken together, these results demonstrated that subacute exposure to C9-13-CPs could have immunomodulatory effects in mice. The present study helps to provide an understanding of the comprehensive health risks posed by C9-13-CPs.