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皮肤中苯甲酮-2 的给药对雄性 Wistar 大鼠免疫系统活性、下丘脑-垂体-甲状腺轴活性和血液学参数的影响。

The effect of dermal benzophenone-2 administration on immune system activity, hypothalamic-pituitary-thyroid axis activity and hematological parameters in male Wistar rats.

机构信息

Department of Biochemical Toxicology, Chair of Toxicology, Medical College, Jagiellonian University, Medyczna 9, PL 30-688, Kraków, Poland.

Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343, Kraków, Poland.

出版信息

Toxicology. 2018 Jun 1;402-403:1-8. doi: 10.1016/j.tox.2018.04.002. Epub 2018 Apr 13.

Abstract

Benzophenones used as UV filters, in addition to the effects on the skin, can be absorbed into the blood and affect the function of certain organs. So far, their effects on the sex hormone receptors and gonadal function have been studied, but not much is known about their potential action on other systems. The aim of the present study was to determine the effect of benzophenone-2 (BP-2) on immune system activity, hypothalamic-pituitary-thyroid (HPT) axis activity and hematological parameters. BP-2 was administered dermally, twice daily at a dose of 100 mg/kg for 4-weeks to male Wistar rats. Immunological and hematological parameters and HPT axis activity were assayed 24 h after the last administration. It was found that BP-2 did not change relative weights of the thymus and spleen and did not exert toxic effect on tymocytes and splenocytes. However, this compound increased proliferative activity of splenocytes, enhanced metabolic activity of splenocytes and thymocytes and nitric oxide production of these cells. In animals exposed to BP-2, the HPT axis activity was increased, as evidenced by reduction in the thyroid stimulating hormone (TRH) level and increase in free fraction of triiodothyronine (fT3) and thyroxin (fT4) in blood. BP-2 had no effect on leukocyte, erythrocyte and platelet counts or on morphology and hemoglobin content in erythrocytes. The conducted research showed that dermal, sub-chronic BP-2 administration evoked hyperthyroidism, increased activity or function of the immune cells but did not affect hematological parameters. We suggest that topical administration of BP-2 leading to a prolonged elevated BP-2 level in blood causes hyperthyroidism, which in turn may be responsible for the increased immune cell activity or function. However, only future research can explain the mechanism and functional importance of the changes in thyroid hormones and immunological parameters observed after exposure to BP-2.

摘要

苯并二酮类物质作为紫外线过滤剂,除了对皮肤的影响外,还可以被吸收到血液中并影响某些器官的功能。到目前为止,人们已经研究了它们对性激素受体和性腺功能的影响,但对它们对其他系统的潜在作用知之甚少。本研究旨在确定二苯甲酮-2(BP-2)对免疫系统活性、下丘脑-垂体-甲状腺(HPT)轴活性和血液学参数的影响。BP-2 经皮给药,每天两次,剂量为 100mg/kg,共 4 周,用于雄性 Wistar 大鼠。末次给药后 24 小时测定免疫和血液学参数及 HPT 轴活性。结果发现,BP-2 未改变胸腺和脾脏的相对重量,对胸腺细胞和脾细胞没有毒性作用。然而,该化合物增加了脾细胞的增殖活性,增强了脾细胞和胸腺细胞的代谢活性以及这些细胞的一氧化氮产生。暴露于 BP-2 的动物中,HPT 轴活性增加,表现为促甲状腺激素(TRH)水平降低,血液中游离三碘甲状腺原氨酸(fT3)和甲状腺素(fT4)增加。BP-2 对白细胞、红细胞和血小板计数或红细胞的形态和血红蛋白含量没有影响。进行的研究表明,皮肤、亚慢性 BP-2 给药会引起甲状腺功能亢进症,增加免疫细胞的活性或功能,但不会影响血液学参数。我们认为,BP-2 的皮肤给药导致血液中 BP-2 水平持续升高,引起甲状腺功能亢进症,这反过来可能是导致免疫细胞活性或功能增加的原因。然而,只有未来的研究才能解释暴露于 BP-2 后观察到的甲状腺激素和免疫参数变化的机制和功能重要性。

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