| Both excessive fluoride and excessive iodide can damage thyroid morphology,and influence TH synthesis and secretion.This indicates that thyroid could possibly be the common toxicity target organ of fluoride and iodide.Study shows that apoptosis is involved in fluoride-caused damage of multiple organs and it also plays an important role in iodide toxicity on thyroid.Endoplasmic reticulum stress is a new apoptosis pathway and the IRE1 pathway is very important in apoptosis induced by endoplasmic reticulum stress.ObjectivesThe purpose of this study is to explore the damage effects of excessive fluoride and/or iodide on rat thyroid and the role of IRE1 pathway in it.Methods1 Toxicity effects on thyroid of rat exposed to excessive fluoride and/or iodide Wistar rats were randomly divided into 8 groups.They were exposed to NaF(5,10,20 mg/L)and/or KIO3(1.685 mg/L)through drinking water.Control group was exposed to tap water.Rats and thyroid were weighed after 2,4 and 8 months of exposure.The HE staining,radioimmunoassay and TUNEL were used to determine thyroid tissue morphology,TH levels in serum and thyroid cell AI.2 Effect on IRE1 pathway in thyroid of rats exposed to excessive fluoride and/or iodideRT-PCR and immunohistochemistry were used to measure mRNA and protein expression level of IRE 1 pathway related molecule.Results1 Compared with control group,the urinary iodide level increased significantly in IH group and three IH+FH groups(P<0.05).It was lower in IH+FH3 group than IH group(P<0.05).Compared with control group,the urinary fluoride level increased significantly in three FH groups,IH+FH2 group and IH+FH3 group(P<0.05).It was lower in IH+FH3 group than FH3 group(P<0.05).2 Compared with control group,weight and organ coefficient of thyroid reduced significantly in IH group and three IH+FH groups(P<0.05).3 Thyroid follicles grew bigger and follicular epithelial cells became flat were observed in IH group,meanwhile,some follicles became smaller.Thyroid follicles became smaller or even no cavity cell clusters were observed in three FH groups and three IH+FH groups,and big follicles were observed in some thyroids.4 Compared with control group,TSH level decreased significantly in FH2 group,FH3 group and three IH+FH groups after 4 and 8 months of exposure(P<0.05).T4 and FT4 level increased significantly in IH group,FH2 group,FH3 group and three IH+FH groups after 2 months(P<0.05).T3 and FT3 level decreased significantly in IH+FH2 group and IH+FH3 group after 8 months(P<0.05).5 Compared with control group,AI of thyroid cell increased significantly in FH3 group and IH+FH3 group after 4 months of exposure(P<0.05).AI of thyroid cell increased significantly in IH group,FH2 group,FH3 groups and three IH+FH groups after 8 months of exposure(P<0.05).6 Compared to control group,mRNA expression levels of GRP78,IRE1,sXBP-1 and CHOP up-regulated significantly in FH3 group and IH+FH3 group after 4 and 8 months of exposure(P<0.05).7 Protein expression levels of GRP78,IRE1 and CHOP up-regulated significantly in FH3 group and IH+FH3 group after 4 and 8 months of exposure.Conclusion1 Excessive fluoride and/or iodide could damage thyroid,and exposure time is a factor.2 Apoptosis is involved in the toxicity induced by excessive fluoride and/or iodide.3 Excessive fluoride and combination of fluoride and iodide can activate IRE1 pathway,which might be one of apoptosis pathway induced by excessive fluoride and combination of fluoride and iodide.4 When both acting on thyroid,excessive fluoride and excessive iodide showed different compound effects on different indicators.The overall effect is no greater than the sum of toxicity caused by the individual excessive fluoride and excessive iodide.The toxicity is determined by the leading one. |
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