Metallokinetic analysis of disposition of vanadyl complexes as insulin-mimetics in rats using BCM-ESR method

Among vanadium's wide variety of biological functions, its insulin-mimetic effect is the most interesting and important. Recently, the vanadyl ion ( 4 oxidation state of vanadium) and its complexes have been shown to normali ze the blood glucose levels of streptozotocin-induced diabetic rats (STZ-ra ts). During our investigations to find more effective and less toxic vanady l complexes, the vanadyl-methylpicolinate complex (VO-MPA) was found to exh ibit higher insulin-mimetic activity and less toxicity than other complexes , as evaluated by both in vitro and in vivo experiments. Electron spin reso nance (ESR) is capable of measuring the paramagnetic species in biological samples. We have developed the in vivo blood circulation monitoring-electro n spin resonance (BCM-ESR) method to analyze the ESR signals due to stable organic radicals in real time. In the present investigation, we have applie d this method to elucidate the relationship between the blood glucose norma lizing effect of VO-MPA and the global disposition of paramagnetic vanadyl species. This paper describes the results of vanadyl species in the circula ting blood of rats following intravenous administration of vanadyl compound s. ESR spectra due to the presence of vanadyl species were obtained in the circulating blood, and their pharmacokinetic parameters were estimated usin g compartment models. The results indicate that vanadyl species are distrib uted considerably to the peripheral tissues, as estimated by BCM-ESR, and e liminated from the body through the urine, as estimated by ESR at 77 K:. Th e exposure of vanadyl species in the blood was found to be enhanced by VO-M PA treatment. Given these results, we concluded that the pharmacokinetic ch aracter of vanadyl species is closely related with the structure and antidi abetic activity of the vanadyl compounds. (C) 2000 Elsevier Science Inc. Al l rights reserved.