Realgar and realgar-containing Liu-Shen-Wan are less acutely toxic than arsenite and arsenate

Liu-Shen-Wan (LSW) is a widely-used traditional Chinese medicine containing realgar (As(4)S(4)).Realgar has been included in many traditional medicines, and is often taken as arsenite for risk assessment in realgar-containing traditional remedies. Is realgar toxicologically similar to arsenite?Mice were orally given LSW (60 and 200mg/kg; 200mg LSW contains 27 mg realgar), realgar (30 mg/kg, equivalent to 21 mg As/kg), and the equivalent As dose as sodium arsenite (NaAsO(2)), or as arsenate (Na(2)HAsO(4)). Acute toxicity and tissue As accumulation were determined 8h later.Arsenite and arsenate increased serum alanine aminotransferase (ALT) levels, indicative of liver injury; blood urea nitrogen (BUN) was also increased by arsenite and arsenate, indicative of nephrotoxicity. No elevations of ALT and BUN were observed in LSW and realgar groups. Histopathology showed more damage in arsenite- and arsenate-treated liver and kidneys, while in realgar- and LSW- treated animals, only mild alterations were seen. Hepatic and renal As contents were dramatically increased to 6200 and 3350ng/g, respectively, after arsenite, but only increased to 260 and 180 ng/g after LSW. The expressions of arsenic-sensitive stress genes, namely metallothionein-1 and heme oxygenase-1, were increased after arsenite or arsenate by 3-10-folds, but were unaltered after LWS and realgar.Realgar and LSW are much less toxic than arsenite and arenate. The use of total As content to evaluate the safety of realgar-containing traditional medicines is not scientifically sound.