Li Chunying, Liang Aihua, Wang Jinhua, Xue Baoyun, Li Hua, Yang Bin, Wang Jingyu, Xie Qing, Nilsen Odd Georg, Zhang Boli
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2011 Jul;36(14):1895-900.
To explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic.
The realgar which was used in the study contains 90% insoluble asenic sulfide (As2S2) and 1.696 mg x kg(-1) soluble arsenic. Two separate experiments were performed: 1) Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. 2) Forty SD rats were randomly divided into four groups: control group and realgar 0.02, 0.08, 0.16 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing.
Asenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g x kg(-1), with the order from high to low blood > kidney > lung > liver > heart > brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day's administration of realgar, and the amount of asenic in organs was in the order of blood > kidney > liver > brain.
Asenic can be absorbed and extensively distributed in various organs or tissesses after realgar administration in rats. Long-term use of realgar caused high asenic accumulation in various tissueses, including blood, kidney, liver, and brain. The nephrotoxicity and hepatotoxicity of realgar could be associated with the asenic accumulation in relative organs. Blood is the target of the most highest distribution and accamulation of asenic after realgar treatment, that could be associated with the efficacy of realgar on the treatment of leakemia.
探讨长期服用雄黄后砷的蓄积及毒性机制，为雄黄临床安全用药提供科学依据。
本研究中使用的雄黄含90%不溶性硫化砷（As2S2）及1.696 mg·kg-1可溶性砷。进行了两项独立实验：1）28只禁食的SD大鼠单次口服0.8 g·kg-1剂量的雄黄，另外4只大鼠给予超滤水作为对照组。给药后分别于0.5、1、2、4、8、16、36小时处死4只大鼠，采集血液、心脏、肝脏、肾脏、肺和脑，检测各器官或血液样本中的砷含量。2）40只SD大鼠随机分为4组：对照组和雄黄0.02、0.08、0.16 g·kg-1组，每组雌雄各5只。大鼠每天灌胃给药雄黄1次，连续90天，对照组给予超滤水。末次给药16小时后，处死禁食大鼠，检测每只大鼠血液、肝脏、肾脏和脑中的砷含量。
单次给予0.16 g·kg-1剂量雄黄后，血液、肝脏、肾脏、心脏、肺和脑中的砷含量均升高，顺序为血液＞肾脏＞肺＞肝脏＞心脏＞脑。血液中的砷含量远高于其他器官。雄黄给药后血液中砷的分布特征可能是其用于治疗白血病的基础。雄黄90天口服给药导致砷在血液、肾脏、肝脏和脑中显著蓄积。砷蓄积量最高的是肾脏，其次是肝脏，推测这与雄黄的肾毒性和肝毒性有关。雄黄给药90天后血液中砷含量最高，各器官中砷含量顺序为血液＞肾脏＞肝脏＞脑。
大鼠服用雄黄后，砷可被吸收并广泛分布于各器官或组织中。长期服用雄黄导致砷在包括血液、肾脏、肝脏和脑在内的各种组织中高度蓄积。雄黄的肾毒性和肝毒性可能与砷在相关器官中的蓄积有关。血液是雄黄给药后砷分布和蓄积最高的靶器官，这可能与雄黄治疗白血病的疗效有关。
