Biological Activity and Toxicity of Various VanadiumIVV Compounds

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Different in vitro methods on cell cultures of various types and tissue hom-ogenates have been applied in order to assess the effects of vanadium on glucose22 and/or fatty acid uptake28 in comparison with insulin.29 The results of one of the most comprehensive tests are depicted in Figure 8.2, relating to the findings on mice fibroblast cells.22

It can be seen in Figure 8.2 that all the tested complexes (and not only those shown in Figure 8.1) increase glucose uptake with a comparable or higher efficiency than that of insulin in the physiologically or pharmacologically relevant concentration level (0.1-1.0 mM). In this concentration range, none of the tested compounds showed toxicity. VO(IV) complexes (which are generally more toxic than V(V)) tend to be more effective insulin mimetics than V(V) complexes. These observations, together with the very similar biological efficacy of all the tested complexes, corroborate the assumption that the complexes undergo transformation during transport and/or within the cell, thus giving rise to active species different from those originally employed (see p. 151). These in vitro studies may be useful for initial screening, but they do not take into account oral bioavailability, which can be tested only in vivo. For in vivo testing, a number of experimental models of diabetes in rodents have been used. Most widely accepted is the streptozotocin (STZ)-induced diabetic rat.30 Moderate to good results have been obtained in vivo too, with many of the V(IV/V) complexes at oral doses of between 0.1 and 0.7mmolkg-1 day-1.17,28 As an illustration,31 the in vivo biological effects of several VO(IV) and V(V) compounds on STZ-diabetic rats are given in Figure 8.3.

Figure 8.2 Glucose intake by siman virus transformed 3T3 mice fibroblasts in the presence of vanadium compounds. The ordinate is a measure for the reduction equivalents originating from glucose. Data are presented for V(IV) (a) and V(V) complexes (b) separately for cells kept without insulin for 72 h (based on Ref. 22). For abbreviations of the complexes see Figure 8.1

Figure 8.2 Glucose intake by siman virus transformed 3T3 mice fibroblasts in the presence of vanadium compounds. The ordinate is a measure for the reduction equivalents originating from glucose. Data are presented for V(IV) (a) and V(V) complexes (b) separately for cells kept without insulin for 72 h (based on Ref. 22). For abbreviations of the complexes see Figure 8.1

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