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 normalize the blood glucose levels of streptozotocin-induced diabetic rats (STZ-rats). During our investigations to find more effective and less toxic vanadyl complexes, the vanadyl-methylpicolinate complex (VO-MPA) was found to exhibit higher insulin-mimetic activity and less toxicity than other complexes, as evaluated by both in vitro and in vivo experiments. Electron spin resonance (ESR) is capable of measuring the paramagnetic species in biological samples. We have developed the in vivo blood circulation monitoring-electron spin resonance (BCM-ESR) method to analyze the ESR signals due to stable organic radicals in real time. In the present investigation, we have applied this method to elucidate the relationship between the blood glucose normalizing effect of VO-MPA and the global disposition of paramagnetic vanadyl species. This paper describes the results of vanadyl species in the circulating blood of rats following intravenous administration of vanadyl compounds. ESR spectra due to the presence of vanadyl species were obtained in the circulating blood, and their pharmacokinetic parameters were estimated using compartment models. The results indicate that vanadyl species are distributed considerably to the peripheral tissues, as estimated by BCM-ESR, and eliminated from the body through the urine, as estimated by ESR at 77 K. The exposure of vanadyl species in the blood was found to be enhanced by VO-MPA treatment. Given these results, we concluded that the pharmacokinetic character of vanadyl species is closely related with the structure and antidiabetic activity of the vanadyl compounds.
Yasui
H
H
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan.
Takechi
K
K
Sakurai
H
H
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D007328:Insulin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D018716:Molecular Mimicry; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine
D007328:Insulin; D014638:Vanadates