Effect Of Ammonium Perchlorate On Iodine Uptake And Antioxidant Capacity Of Thyroid

Objective Ammonium Perchlorate (AP) is a white crystalline powder, commonly used as solid propellants in aerospace rockets and missiles. In the industrial production and process of using, the dust of AP will have potential risk to human body through several different approaches. Studies have found that AP has obvious toxicity on thyroid function. We intend to explore the effect of AP on iodine uptake and antioxidant capacity of thyroid in rat and explain the role of AP on thyroid toxicity mechanism. It could provide a scientific basis for the prevention and control of thyroid gland health risks in the occupational groups exposed to AP.Methods Twenty SD male rats were randomly divided into three AP treated groups and a control group with five rats in each group. The three AP treated groups were exposed to AP at dosage of 130mg/kg (low), 260mg/kg (moderate) and 520mg/kg (high). The treatments were daily conducted by intragastric administration for 13 weeks based on body weight which was weighed once a week. The capacity of intragastric administration were 1ml/100g body weight. We collected obital venous blood and separated the serum which was measured thyroid hormones by radioimmunoassay at the sixth and thirteenth weeks of exposure. After thirtee weeks of exposure, we give 4μCi ¹³¹I to the rats by gavage and then test thyroid iodine uptake (¹³¹I) rate after 24h. When finished, rats were sacrificed and dissected. We weighed the removed thyroid and calculated organ coefficient. One side of the thyroid was homogenized and measured the malondialdehyde (MDA) and superoxide dismutase (SOD) with a kit. A portion of the other side of the thyroid was used to extract the total RNA by Trizol kit. Then through the reversed transcription and PCR amplificated, we got the producet of sodium iodide symporter (NIS) mRNA. The relative amount of NIS mRNA expression were represented by NIS /β-actin ratio of gray and measured by the gel scanning imaging system. Meanwhile, the residual thyroid tissue was fixed with 2.5% glutaraldehyde, done to chips and observed the alteration of thyroidal ultrastructure.Results Body weight of each treated group rats were significantly decreased compared with the control group after exposed to AP for 13 weeks (P<0.05). But the organ coefficient of the thyroid were significantly increased, especially, the moderate and high dose groups statistically significant (P<0.05 or P<0.01). Serum thyroid hormone levels: At the sixth week exposed to AP, serum FT₄ level of each treated group was deceased compared with control group, and that moderate, high dose groups were statistically significant (P<0.01). At the thirteenth week, serum FT₄ level of each dose group were significantly lower than the control(P<0.01).At the sixth week, thyroid stimulating hormone (TSH) was elevated in every treated group compared with control group, but only the high dose group was significantly increased (P<0.01).At the thirteenth week, the TSH level changes the same as with the sixth week. Thyroid radioiodine uptake rate and the expression of NIS mRNA: Thyroid radioiodine uptake rate of each treated group was significantly depressed (P<0.01). The expression of NIS mRNA was increased in each treated group, only the high dose group was significantly increased (P<0.01). The contents of MDA and the activities of SOD of thyroid: The contents of MDA in the moderate and high dose groups were significantly increased (P<0.01), while the activities of SOD in all treated groups were significantly increased (P<0.05). Ultrastructural pathological images of thyroid: The ultrastructural pathological images of thyroid in all treated groups exhibited a dose-response relationship and showed shrunk follicular lumen, thicken basement membrane, mitochondrion and endoplasmic reticulum swelling and extension severely in epithelial cells.Conclusion This study showed that target organ of AP is the thyroid. Competitive inhibition of thyroid iodine uptake can result in deficient iodineand altered thyroid hormone homeostasis. Declined FT₄ level and elevated TSH level could lead to the expression of NIS mRNA compensatory increasing and thyroid enlargement and hyperplasia with body weight growth retardation. In addition, AP could induce oxidative damage in thyroid and the ultrastructural pathological images showed obvious swelling and extension of mitochondrion and endoplasmic reticulum in epithelial cells. In conclusion, these results show that AP has obvious toxicity on thyroid and provides a reliable experimental evidence for occupational hazards of AP.