In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system

Abstract

In this study, thein vivohypoglycemic effect of a donut-shaped polyanion salt (NH4)14[Na@P5W30O110]$31H2O{NaP5W30} and its Ag-containing derivative K14[Ag@P5W30O110]$22H2O$6KCl {AgP5W30}, as wellas their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study,Wistaralbinorats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5,10, and 20 mg per kg per b.w.) of both investigated polyoxotungstates. The blood glucose levels,measured before and after 2, 4 and 6 h polyoxotungstate application, showed that both studiedcompounds induced the most pronounced and time dependent glucose lowering effects at the doses of20 mg kg1. Thus, daily doses of 20 mg kg1were administered toWistar albinorats orally for 14 days infurther toxicity examinations. The serum glucose concentration and biochemical parameters of kidneyand liver function, as well as a histopathological analysis of kidney and liver tissues were evaluated 14days after the polyoxotungstate administration. Both investigated compounds did not induce statisticallysignificant alterations of the serum glucose and uric acid concentrations, as well as some of the liverfunction markers (serum alanine and aspartate aminotransferases, and alkaline phosphatase activities).However, the significant decrease in serum total protein and albumin concentrations and the increase inbiochemical parameters of renal function–serum urea (up to 63.1%) and creatinine concentrations (upto 23.3%) were observed for both polyoxotungstates. In addition, the detected biochemical changeswere in accordance with kidney and liver histhopathological analysis. Accordingly, the hepatotoxic andnephrotoxic effects of these potential antidiabetic polyoxotungstates could be considered as mild.