Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity

A toxicity evaluation of two Keggin-type heteropolytungstates, K₇[Ti₂PW₁₀O₄₀]·6H₂O and K₆H[SiV₃W₉O₄₀]·3H₂O, with different inhibitory potencies toward acetylcholinesterase activity (IC₅₀ values of 1.04×10^-6 and 4.80×10^-4mol/L, respectively) was performed. Wistar albino rats were orally treated with single doses (5 and 50mg/kg) of both investigated compounds. The biochemical parameters of renal (serum urea and creatinine) and liver function (direct and total bilirubin, alanine transaminase, and aspartate aminotransferase) were determined after 24h and 14days. A histopathological analysis of liver tissue was carried out 14days after the polyoxotungstate administration. Both applied doses of the investigated compounds did not induce statistically significant alterations of the renal function markers. However, the polyoxotungstate treatment caused an increase in the activities of serum alanine transaminase and aspartate aminotransferase in a time- and concentration-dependent manner, although statistically significant changes in bilirubin concentrations were not observed. Furthermore, the detected hepatotoxic effect was confirmed by histhopathological analysis that suggested some reversible liver tissue damage two weeks after the treatment, especially in the case of K₆H[SiV₃W₉O₄₀]·3H₂O. Accordingly, the toxicity of these two polyoxotungstates with anti-acetylcholinesterase effect cannot be considered as a severe one, but their potential clinical application would require a more complex toxicological study.