Objective: To conduct a comparative study on the toxic reaction of Niuhuang Jiedu tablets containing Calculus Bovis (Niuhuang) from different sources in mice

in order to explore the mechanism of chronic arsenic poisoning clinically caused by Niuhuang Jiedu tablets. Method: Test sample Niuhuang Jiedu tablets were respectively made by using natural Calculus Bovis

Bovis Calculus Artificial

and Bovis Calculus Sativus

with no Calculus Bovis element and no Realgar element

according to Chinese Pharmacopoeia (Version 2015). The same dose of test sample single Realgar was used for control. Each Niuhuang Jiedu tablets group was divided into low

middle and high-dose groups

ICR mice were intragastrically administered with drugs for 28 days

then the toxic reaction was observed during the period of drug administration. After drug administration

these mice were put to death. Their blood samples were collected to test liver and kidney function

and tissues of heart

liver

spleen

lung and kidney were collected for histopathological examination and ultrastructure observation under electronic microscopy. Result: In each test group

no toxic reaction was observed during drug administration. No gross lesion was observed in viscera and skins after the mice were put to death. And no clear toxic effect of Realgar on liver and kidney functions was found in blood biochemistry examination. In each Niuhuang Jiedu tablets group

no change in histopathology and ultrastructure under electronic microscopy was found. But in high-dose single Realgar group

the histopathological examination showed that in hepatic lobule

hepatocytes became enlarged

and glycogen accumulated in cytoplasma according to hematoxylin-eosin (HE) staining

which were further confirmed by periodic acid Schiff reaction (PAS) staining. Ultrastructure under electronic microscopy showed in hepatocytes focal cytoplasm dissolutions

and glycogen granules were found inside. Conclusion: No obvious toxic reaction was found in ICR mice after administration with Niuhuang Jiedu tablets containing bovis calculus from different sources for 28 days

but the same dose of single Realgar could cause liver toxicity. It is suggested that other ingredients in Niuhuang Jiedu tablets combined with Realgar can significantly reduce the concentrations of soluble arsenic and arsenic valence state

thus reducing the toxicity of Realgar.