bis(maltolato)oxovanadium(iv) and acetyl-acetonate

The aim of this study was to investigate the mechanism of permeation and cytotoxicity of vanadium compounds, [VO(acac)2], [VO(ma)2], and vanadate.. Absorptive transport were carried out in Caco-2 monolayers grown on transwell inserts. Vanadium was quantified using inductively coupled plasma atomic emission spectrometry (ICP-AES). The change of Caco-2 cells in the microvilli morphology and F-actin structure was visualized by transmission electron microscopy and confocal laser scanning microscopy.. The three vanadium compounds were taken up by Caco-2 cells via simple passive diffusion. [VO(acac)2] were mainly transcellularly transported and exhibited the highest apparent permeabilty coefficients (8.2 x 10(-6) cm(-1)). The cell accumulation of [VO(acac)2] was found to be greater than that of [VO(ma)2], and vanadate caused much less accumulation than the other two compounds. Vanadium compounds induced intracellular reactive oxygen species, reduced the transepithelial electric resistance, caused morphological change in microvilli, and led to different perturbation of F-actin structure.. The three compounds exhibited different permeability due to different diffusion process and cellular uptake. The toxicity of vanadium complexes on Caco-2 monolayer involved F-actin-related change of tight junction and impairment of microvilli. The toxicity was also related to elevated intracellular reactive oxygen species (ROS) and their cellular accumulation.

Topics: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Actins; Caco-2 Cells; Cell Membrane Permeability; Cell Survival; China; Diffusion; Electric Impedance; Formazans; Humans; Hydrogen Peroxide; Hydroxybutyrates; Hypoglycemic Agents; Microscopy, Confocal; Microscopy, Electron, Scanning; Microvilli; Pentanones; Pyrones; Reactive Oxygen Species; Spectrophotometry, Atomic; Superoxides; Tetrazolium Salts; Vanadates; Vanadium Compounds

1. Vanadium compounds can mimic actions of insulin through alternative signalling pathways. The effects of three organic vanadium compounds were studied in non-ketotic, streptozotocin-diabetic rats: vanadyl acetylacetonate (VAc), vanadyl 3-ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM). A simple inorganic vanadium salt, vanadyl sulphate (VS) was also studied. 2. Oral administration of the three organic vanadium compounds (125 mg vanadium element 1(-1) in drinking fluids) for up to 3 months induced a faster and larger fall in glycemia (VAc being the most potent) than VS. Glucosuria and tolerance to a glucose load were improved accordingly. 3. Activities and mRNA levels of key glycolytic enzymes (glucokinase and L-type pyruvate kinase) which are suppressed in the diabetic liver, were restored by vanadium treatment. The organic forms showed greater efficacy than VS, especially VAc. 4. VAc rats exhibited the highest levels of plasma or tissue vanadium, most likely due to a greater intestinal absorption. However, VAc retained its potency when given as a single i.p. injection to diabetic rats. Moreover, there was no relationship between plasma or tissue vanadium levels and any parameters of glucose homeostasis and hepatic glucose metabolism. Thus, these data suggest that differences in potency between compounds are due to differences in their insulin-like properties. 5. There was no marked toxicity observed on hepatic or renal function. However, diarrhoea occurred in 50% of rats chronically treated with VS, but not in those receiving the organic compounds. 6. In conclusion, organic vanadium compounds, in particular VAc, correct the hyperglycemia and impaired hepatic glycolysis of diabetic rats more safely and potently than VS. This is not simply due to improved intestinal absorption, indicating more potent insulin-like properties.

Topics: Administration, Oral; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Disinfectants; Glucokinase; Glucose; Hydroxybutyrates; Hypoglycemic Agents; Injections, Intraperitoneal; Insulin; Islets of Langerhans; Ligands; Liver; Liver Glycogen; Male; Muscles; Organometallic Compounds; Pentanones; Phosphoenolpyruvate Carboxykinase (GTP); Pyrones; Pyruvate Kinase; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Vanadates; Vanadium Compounds