Lan Zhou, Hyung Kim Tae, Shun Bi Kai, Hui Chen Xiao, Sik Kim Hyung
Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, People's Republic of China; Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-Dong, Geumjung-Gu, Busan, 609-735, Republic of Korea.
Environ Toxicol. 2015 Jan;30(1):83-91. doi: 10.1002/tox.21897. Epub 2013 Aug 9.
Triclosan (TCS) is considered a potent endocrine disruptor that causes reproductive toxicity in non-mammals, but it is still unclear exactly whether TCS has adverse effects on the sperm or reproductive organs in mammals. In this study, we aimed to evaluate the distribution status of TCS in male reproductive organs of rats, and seek the correlation with the TCS-induced sperm toxicity or reproductive organ damage. Male rats were intragastrically administered with TCS at a dose of 50 mg/kg, the kinetics of TCS in the plasma and reproductive organs were investigated. TCS in testes and prostates both showed a lower-level distribution compared to that in the plasma, which indicates it has no tendency to accumulate in those organs. However, TCS in the epididymides showed a longer elimination half-life (t1/2 z), a longer the mean retention time (MRT), and a lower clearance (CLZ /F) compared with those in the plasma. Besides, the ratios of mean area under the concentration-time curve (AUC)(0-96 h(epididymides/plasma)) and AUC(0-∞(epididymides/plasma)) were 1.13 and 1.51, respectively. These kinetic parameters suggest TCS has an accumulation tendency in the epididymides. Based on this, we investigated the TCS-induced sperm toxicity and histopathological changes of reproductive organs in rats. TCS was given intragastrically at doses of 10, 50, and 200 mg/kg for 8 weeks. Rats treated with the high dose (200 mg/kg) of TCS showed a significant decrease in daily sperm production (DSP), changes in sperm morphology and epididymal histopathology. Considering the histopathological change in the epididymides, TCS may induce the epididymal damage due to the epididymal accumulation of that.
三氯生(TCS)被认为是一种强效内分泌干扰物,可导致非哺乳动物出现生殖毒性,但TCS对哺乳动物的精子或生殖器官是否有不良影响仍不明确。在本研究中,我们旨在评估TCS在大鼠雄性生殖器官中的分布状况,并探寻其与TCS诱导的精子毒性或生殖器官损伤之间的相关性。给雄性大鼠灌胃给予剂量为50 mg/kg的TCS,研究TCS在血浆和生殖器官中的动力学。睾丸和前列腺中的TCS分布水平均低于血浆中的水平,这表明它没有在这些器官中蓄积的倾向。然而,与血浆中的情况相比,附睾中的TCS消除半衰期(t1/2 z)更长,平均保留时间(MRT)更长,清除率(CLZ /F)更低。此外,浓度-时间曲线下平均面积(AUC)(0 - 96 h(附睾/血浆))和AUC(0 - ∞(附睾/血浆))的比值分别为1.13和1.51。这些动力学参数表明TCS在附睾中有蓄积倾向。基于此,我们研究了TCS诱导的大鼠精子毒性和生殖器官的组织病理学变化。以10、50和200 mg/kg的剂量给大鼠灌胃给予TCS,持续8周。用高剂量(200 mg/kg)TCS处理的大鼠每日精子生成量(DSP)显著降低,精子形态和附睾组织病理学发生改变。考虑到附睾的组织病理学变化,TCS可能因其在附睾中的蓄积而导致附睾损伤。