Dimethylarsenic acid (DMA) accumulation positively correlates with realgar-induced subchronic toxicity in rats

Abstract

The toxicity of realgar depends largely on different arsenic species accumulation and distribution in the body. Here, after continuous oral administration of different doses of realgar for 90 days and subsequent 60-day withdrawal period, clinical observations, food consumption, body weights, blood biochemistry, hematology, and histomorphological examination of rats were performed. Realgar 40mg{middle dot}kg-1{middle dot}d-1 and 170 mg{middle dot}kg-1{middle dot}d-1 of realgar (which is equivalent to 40-fold and 100-fold the maximum clinical dose, respectively) can cause toxicity in rats, including degreased body weight, peripheral blood neutrality abnormal ratio of granulocytes and lymphocytes, hypercoagulability of the blood, liver and kidney tissue damage, liver and kidney may be the main toxic target organs of realgar. The no observed adverse effect level (NOAEL) dose is 10 mg{middle dot}kg-1. At the same time, the content and distribution of arsenic species in tissues were determined. The content of total arsenic (tAs) and Dimethylarsenic acid (DMA) in the tissues of the realgar group was significantly higher than those of the control group. After 60 days of discontinuation, the DMA content in the realgar group decreased, but it was still higher than that in the control group, and liver and kidney damage occurred during the administration period basically returned to normal. Therefore, the authors speculated that when the DMA content in the tissue exceeds a certain range, liver and kidney toxicity will be induced. However, when the DMA content is lower than the above threshold after drug withdrawal, the liver and kidney lesions can return to normal.