Immunotoxic Effect Of Perfluorooctane Sulfonate And Perfluorooctanoic Acid In Balb/c Mice

Because of the characteristic of long-term residual, bioaccumulative, semi-volatile and highly toxic properties, persistent organic pollutants (POPs) has become one of the most controversial environmental pollutants. In May 2009, the Stockholm Convention decided to listed perfluorooctane sulfonate (PFOS) and other eight chemical substances as the POPs. The potential toxic effects of PFOS have attracted wide attention. Perfluorooctanoic acid (PFOA) as potential carcinogens has also aroused extensive attention. In this study, on the basis of the current research, BALB/c mice were fed a regular (RD) or high-fat diet (HFD). They were then exposed to PFOS (0,5, and 20 mg/kg/d) for 14 days, to determine if more fat could eliminate the toxic effect of PFOS on the immune system. These datas are useful for understanding the toxicological effects induced by PFOS and PFOA, and provide evidence for the mechanism of toxicity of this agent.The results showed that after 14 days of PFOS exposure, in the RD-exposure group, the body weight significantly decreased and the immune organs showed considerable atrophy. Histopathological analyses showed that the corticomedullary junction of the thymus was indistinguishable, sinus expansion in the spleen appeared, and increased apoptosis of thymocytes was observed. Gene expressions of the peroxisome proliferator-activated receptor-alpha (PPARa) and interleukin-1 beta (IL-1β) were upregulated in the thymus and spleen in all exposure groups, but there was no significant change compared to the control group. In the HFD group, all of these phenomena were not eliminated. After exposed to PFOA, the body weight of the mice in RD exposure groups were also significantly decreased, the immune organs showed a serious atrophy, and the number of lymphocytes in the blood had a significant reduction. Histological analysis showed that the corticomedullary junction of thymus was not distinguishable, and spleen had a fibrous hyperplasia. Increased apoptosis of thymocytes was also observed. However, superoxide dismutase (SOD) activity and hydrogen peroxide (H2O2) concentration of spleen did not change significantly. Gene expressions of the PPARa, peroxisome proliferator-activated receptor-gamma (PPARγ), IL-1βand glucocorticoid receptor (GR) were upregulated in the thymus and spleen in all exposure groups. In the HFD exposure group, these phenomena still existed, but the damage reduced slightly, and the gene expression did not change significantly. Transmission electron microscopy (TEM) results showed similar results after exposure of PFOS and PFOA. Mitochondria swelled and became cavitated, nuclei deformity, and lipofuscin granules and vacuoles appeared in the thymus and spleen. The result of primary cultures of thymocye and splenocyte showed that high concentrations of PFOS and PFOA were able to significantly induce lymphocyte death. However, apoptosis was no significant change, which was different from the in vivo results. In conclusion, PFOS and PFOA can cause the atrophy of the spleen and thymus, changes in the ultrastructure, senescence, as well as degeneration of immune organs. Furthermore, the increased intake of lipids cannot eliminate these phenomena. PFOS and PFOA may interfere with lipid metabolism, and then affect the immune organ indirectly. But this is not the only way. PFOS and PFOA may cause immunosuppression combined with a variety of ways.