Dai Gui-Dong, Cui Lun-Biao, Song Ling, Zhao Ren-Zhen, Cheng Jian-Feng, Liu Mei-Xia, Zhou Jian-Wei, Xiao Hang, Wang Xin-Ru
Institute of Toxicology, Nanjing Medical University, Jiangsu, China.
Biomed Environ Sci. 2005 Aug;18(4):211-9.
To provide more information for rational evaluation of potential risks of terephthalic acid (TPA), we studied the effects of TPA on rats' bladders in 90 days after TPA exposure.
Sprague Dawley rats were subdivided into five groups, ingesting 0%, 0.04%, 0.2%, 1%, and 5% TPA respectively for a sub-chronic feeding study lasting for 90 days. Urine, serum and samples of brain, liver, lung, kidney, bladder, etc. were collected and analyzed.
TPA ingesting decreased the value of urinary pH, and increased the contents of Ca2+, Zn2+, Mg2+, Na+, K+ in urine. The volume of 24 h urine was significantly increased in male rats in the 1% and 5% TPA groups. Urinary white sediment was found in both sexes, and its formation in male rats seemed more susceptible than that in female rats. Alpha 2u-globulin (AUG) in serum and urine of male rats was markedly increased in a dose-dependent manner. Fifteen cases of hyperplasia (simple or atypical) were determined in the 5% TPA ingesting group, 14/52 in male rats and 1/23 in female rats. Among them 3 male rats had no stone or calculus. Those with either bladder stones or hyperplasia were accompanied with urinary white sediments.
White sediment accompanied with elevated urine AUG is the basis of TPA induced urolith formation, and is also associated with TPA induced bladder epithelial cell proliferation. It can act as an early biomarker for the potential toxic effect of TPA.
为合理评估对苯二甲酸（TPA）的潜在风险提供更多信息，我们研究了TPA暴露后90天内对大鼠膀胱的影响。
将斯普拉格-道利大鼠分为五组，分别摄入0%、0.04%、0.2%、1%和5%的TPA，进行为期90天的亚慢性喂养研究。收集并分析尿液、血清以及脑、肝、肺、肾、膀胱等组织样本。
摄入TPA降低了尿液pH值，增加了尿液中Ca2+、Zn2+、Mg2+、Na+、K+的含量。1%和5%TPA组雄性大鼠的24小时尿量显著增加。雌雄大鼠均出现尿白色沉淀物，雄性大鼠中其形成似乎比雌性大鼠更易发生。雄性大鼠血清和尿液中的α2u球蛋白（AUG）呈剂量依赖性显著增加。在摄入5%TPA的组中确定了15例增生（单纯性或非典型性），雄性大鼠中有14/52例，雌性大鼠中有1/23例。其中3只雄性大鼠无结石。有膀胱结石或增生的大鼠均伴有尿白色沉淀物。
伴有尿液AUG升高的白色沉淀物是TPA诱导尿路结石形成的基础，也与TPA诱导的膀胱上皮细胞增殖有关。它可作为TPA潜在毒性作用的早期生物标志物。
