OBJECTIVETo explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic.

METHODThe 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.

RESULTAsenic 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.

CONCLUSIONAsenic 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.