Zhang Bin-Bin, Li Wen-Kai, Hou Wei-Yu, Luo Ya, Shi Jing-Zhen, Li Cen, Wei Li-Xin, Liu Jie
Key Lab for Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China.
School of Public Health, Zunyi Medical University, Zunyi 563000, China.
Toxicol Appl Pharmacol. 2017 Sep 15;331:76-84. doi: 10.1016/j.taap.2017.05.021. Epub 2017 May 20.
Mercury sulfides are used in Ayurvedic medicines, Tibetan medicines, and Chinese medicines for thousands of years and are still used today. Cinnabar (α-HgS) and metacinnabar (β-HgS) are different from mercury chloride (HgCl) and methylmercury (MeHg) in their disposition and toxicity. Whether such scenario applies to weanling and aged animals is not known. To address this question, weanling (21d) and aged (450d) rats were orally given Zuotai (54% β-HgS, 30mg/kg), HgS (α-HgS, 30mg/kg), HgCl (34.6mg/kg), or MeHg (MeHgCl, 3.2mg/kg) for 7days. Accumulation of Hg in kidney and liver, and the toxicity-sensitive gene expressions were examined. Animal body weight gain was decreased by HgCl and to a lesser extent by MeHg, but unaltered after Zuotai and HgS. HgCl and MeHg produced dramatic tissue Hg accumulation, increased kidney (kim-1 and Ngal) and liver (Ho-1) injury-sensitive gene expressions, but such changes are absent or mild after Zuotai and HgS. Aged rats were more susceptible than weanling rats to Hg toxicity. To examine roles of transporters in Hg accumulation, transporter gene expressions were examined. The expression of renal uptake transporters Oat1, Oct2, and Oatp4c1 and hepatic Oatp2 was decreased, while the expression of renal efflux transporter Mrp2, Mrp4 and Mdr1b was increased following HgCl and MeHg, but unaffected by Zuotai and HgS. Thus, Zuotai and HgS differ from HgCl and MeHg in producing tissue Hg accumulation and toxicity, and aged rats are more susceptible than weanling rats. Transporter expression could be adaptive means to reduce tissue Hg burden.
硫化汞在阿育吠陀医学、藏医学和中医中已使用了数千年，至今仍在使用。朱砂（α-HgS）和黑辰砂（β-HgS）在分布和毒性方面与氯化汞（HgCl）和甲基汞（MeHg）不同。这种情况是否适用于断奶和老龄动物尚不清楚。为了解决这个问题，给断奶（21日龄）和老龄（450日龄）大鼠口服坐台（54%β-HgS，30mg/kg）、HgS（α-HgS，30mg/kg）、HgCl（34.6mg/kg）或MeHg（MeHgCl，3.2mg/kg），持续7天。检测肾脏和肝脏中汞的蓄积以及毒性敏感基因的表达。HgCl使动物体重增加减少，MeHg的影响较小，而坐台和HgS处理后体重未改变。HgCl和MeHg导致组织汞大量蓄积，增加肾脏（kim-1和Ngal）和肝脏（Ho-1）损伤敏感基因的表达，但坐台和HgS处理后这种变化不存在或很轻微。老龄大鼠比断奶大鼠对汞毒性更敏感。为了研究转运体在汞蓄积中的作用，检测了转运体基因的表达。HgCl和MeHg处理后，肾脏摄取转运体Oat1、Oct2和Oatp4c1以及肝脏Oatp2的表达降低，而肾脏外排转运体Mrp2、Mrp4和Mdr1b的表达增加，但坐台和HgS处理未产生影响。因此，坐台和HgS在产生组织汞蓄积和毒性方面与HgCl和MeHg不同，老龄大鼠比断奶大鼠更敏感。转运体表达可能是减轻组织汞负荷的适应性手段。
