Vanadium in Biological Action: Chemical, Pharmacological Aspects, and Metabolic Implications in Diabetes Mellitus (original) (raw)
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Potential Use of Vanadium Compounds in Therapeutics
Current Medicinal Chemistry, 2010
Vanadium is a trace element present in practically all cells in plants and animals. While the essentiality of vanadium for human beings remains to be well established, vanadium has become an increasingly important environmental metal. Vanadium compounds exert a variety of biological activities and responses. At pharmacological doses, vanadium compounds display relevant biological actions such as insulin and growth factor mimetic or enhancing effects, as well as osteogenic and cardioprotective activity. On the other hand, depending on the nature of compounds and their concentrations, toxicological actions and adverse side effects may also be shown. Nevertheless, the toxic effects may be useful to develop new antitumoral drugs. In this review, the authors summarize current knowledge and new advances on in vitro and in vivo effects of inorganic and organically-chelated vanadium compounds. The effects of vanadium derivatives on some cellular signaling pathways related to different diseases are compiled. In particular, the pathways relevant to the insulin mimetic, osteogenic, cadioprotective and antitumoral actions of vanadium compounds have been comprehensively reviewed. The knowledge of these intracellular signaling pathways may facilitate the rational design of new vanadium compounds with promising therapeutic applications as well as the understanding of secondary side effects derived from the use of vanadium as a therapeutic agent.
In vitro study of the antidiabetic behavior of vanadium compounds
Coordination Chemistry Reviews, 2017
The paper deals with the so far most efficient antidiabetic transition metal compound family. It focuses on the species distribution of the most frequently studied vanadium(IV,V) compounds in biology: in the gastro-intestinal tract (being important in absorption of the compounds), the blood serum (very likely the main route of their transport), the whole blood (recently the role of the red blood cells are also assumed in their transport) and in the cells (where glutathione and ATP may be the most important redox and complex formation partners of the original vanadium-"insulinomimetics"). The discussed details fit into the general view, but far from a complete and clear understanding of the pharmacodynamics of these antidiabetics. A lot more in vitro and mostly in vivo studies are necessary to justify their real clinical use. Contents 2.4. Speciation of vanadium with high molecular mass (HMM) constituents of blood serum 2.5 Speciation of vanadium(IV) and vanadium(V) in blood serum 2.6. Interactions of vanadium in the whole blood 2.7. Speciation of vanadium in the cells 3. Conclusions Acknowledgements References Abbreviations: GI, gastrointestinal; LMM, low molecular mass; HMM, high molecular mass; HIV, human immunodeficiency virus; DM, diabetes mellitus; STZ, streptozotocin; BMOV, bis(maltolato)oxovanadium(IV); BEOV, bis(ethylmaltolato)oxovanadium(IV); acac, acetylacetone; mal, maltol (3-hydroxy-2-methyl-4-pyrone); imal, isomaltol [1-(3-hydroxy-2furanyl) ethanone]; amal, allomaltol (3-hydroxy-6-methyl-4-pyrone); emal, ethyl maltol (3hydroxy-2-ethyl-4-pyrone); ipmal, isopropyl maltol (3-hydroxy-2-isopropyl-4-pyrone); alx, allixin (3-hydroxy-5-methoxy-6-methyl-2-pentyl-4-pyrone); koj, kojic acid [5-Hydroxy-2-(hydroxymethyl)-4-pyrone]; cur, curcumin; hpno, 2-hydroxypyridine N-oxide; dhp, 3hydroxy-1,2-dimethyl-4(1H)-pyridone; hopy, 1-hydroxy-2(1H)-pyrimidone; dmhopy, 1hydroxy-4,6-dimethyl-2(1H)-pyrimidone; mhopy, 1-hydroxy-6-methyl-2(1H)-pyrimidone; pic, picolinic acid; 6mpic, 6-methylpicolinic acid; 6etpic, 6-ethylpicolinic acid; 5ipic, 5iodopicolinic acid; 3mpic, 3-methylpicolinic acid; 3hpic, 3-hydroxypicolinic acid; dipic, 2,6dipicolinic acid; biguad, biguanide; metf, metformin (N',N'-dimethylbiguanide); mpno, 2mercaptopyridine N-oxide; ROS, reactive oxygen species; XANES, X-ray absorption near edge structure; Tf, transferrin(human); apoTf, apotransferrin(human); HSA, human serum transferrin; his, histidine; asp, aspartic acid; tyr, tyrosine; gly, glycine; NTS, N-terminal (binding) site; ATCUN, amino terminal Cu(II)-and Ni(II)-binding; MBS, multiple binding sites; IgG, immunoglobulin G; EPR, electron paramagnetic resonance; CD, circular dichroism; ICP-MS, inductively coupled plasma mass spectrometry; LC50, lethal concentration 50%; Hb, hemoglobin; RBC, red blood cell; GSH, glutathione; GSSG,
Molecular and Cellular Biochemistry, 1998
We demonstrated in 1985 that vanadium administered in the drinking water to streptozotocin (STZ) diabetic rats restored elevated blood glucose to normal. Subsequent studies have shown that vanadyl sulfate can lower elevated blood glucose, cholesterol and triglycerides in a variety of diabetic models including the STZ diabetic rat, the Zucker fatty rat and the Zucker diabetic fatty rat. Long-term studies of up to one year did not show toxicity in control or STZ rats administered vanadyl sulfate in doses that lowered elevated blood glucose. In the BB diabetic rat, a model of insulin-dependent diabetes, vanadyl sulfate lowered the insulin requirement by up to 75%. Vanadyl sulfate is effective orally when administered by either single dose or chronic doses. It is also effective by the intraperitoneal route. We have also been able to demonstrate marked long-terrn effects of vanadyl sulfate in diabetic animals following treatment and withdrawal of vanadyl sulfate. Because vanadyl sulfate is not well absorbed we have synthesized and tested a number of organic vanaditun compounds. One of these, bismaltolato-oxovanadiurn IV (BMOV), has shown promise as a therapeutic agent. BMOV is 2-3x more potent than vanadyl sulfate and has shown less toxicity. Recent studies from our laboratory have shown that the effects of vanadium are not due to a decrease in food intake and that while vanadium is deposited in bone it does not appear to affect bone strength or architecture. The mechanism of action of vanadium is currently under investigation. Several studies indicate that vanadiun is a phosphatase inhibitor and that vanadium can activate serine/threonine kineses distal to tbe insulin receptor presumably by preventing dephosphorylation due to inhibition of phosphatases Short-term clinical trials using inorganic vanadium compounds in diabetic patients have been promising.
Molecular and Cellular Biochemistry, 1995
The stability of 11 vanadium compounds is tested under physiological conditions and in administration fluids. Several compounds including those currently used as insulin-mimetic agents in animal and human studies are stable upon dissolution in distilled water but lack such stability in distilled water at pH 7. Complex lability may result in decomposition at neutral pH and thus may compromise the effectiveness of these compounds as therapeutic agents; Even well characterized vanadium compounds are surprisingly labile. Sufficiently stable complexes such as the VEDTA complex will only slowly reduce, however, none of the vanadium compounds currently used as insulin-mimetic agents show the high stability of the VEDTA complex. Both the bis(maltolato)oxovanadium(IV) and peroxovanadium complexes extend the insulin-mimetic action of vanadate in reducing cellular environments probably by increased lifetimes under physiological conditions and/or by decomposing to other insulin mimetic compounds. For example, treatment with two equivalents of glutathione or other thiols the (dipicolinato)peroxovanadate(V) forms (dipicolinato)oxovanadate(V) and vanadate, which are both insulin-mimetic vanadium(V) compounds and can continue to act. The reactivity of vanadate under physiological conditions effects a multitude of biological responses. Other vanadium complexes may mimic insulin but not induce similar responses if the vanadate formation is blocked or reduced. We conclude that three properties, stability, lability and redox chemistry are critical to prolong the half-life of the insulin-mimetic form of vanadium compounds under physiological conditions and should all be considered in development of vanadium-based oral insulin-mimetic agents. (Mol Cell Biochem 153: 17-24, 1995) Key words." vanadium chemistry, vanadium biochemistry, compound stability, compound lability, insulin-mimetic, metabolic involvement Abbreviations: ADP-adenosine 5'-diphosphate; ATP-adenosine 5'-triphosphate, ADP-V-adenosine 5'-diphosphate-vanadate; bpV-bis(peroxo)oxovanadium(V); (bpV)2-bis(peroxo)oxovanadium(V) dimer; bpVpic-bis(peroxo)picolinatooxovanadate(V); ~3C-carbon-13; EDTA-ethylenediaminetetraacetic acid; EPR-electron paramagnetic resonance; EXSY-exchange spectroscopy; 'H-proton; HSG-glutathione; NAD-[3-nicotinarnide adenine dinucleotide; NADP-13nicotinamide adenine dinucleotide phosphate; NADV-[3-nicotinamide adenine dinucleotide vanadate; NMR-nuclear magnetic resonance (also referred to as magnetic resonance imaging); pVdipic-(dipicolinato)peroxovanadate(V); Veit-(citrato)dioxovanadate(V); VEDTA-(ethylenediaminetetraacetato)dioxovanadate(V); Vmalto-bis(maltolato)oxovanadium(IV); Voxal-bis(oxalato)dioxovanadate(V); 51V-vanadium-51; V 1-vanadate monomer; V 2-vanadate dimer; V 4-vanadate tetramer; V 5-vanadate pentamer; UV-vis spectroscopy-ultraviolet-visible spectroscopy
British Journal of Pharmacology, 1999
Vanadium compounds can mimic actions of insulin through alternative signalling pathways. The eects 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 l 71 in drinking¯uids) 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 ecacy 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 dierences in potency between compounds are due to dierences 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.
Vanadium Compounds with Antidiabetic Potential
International Journal of Molecular Sciences
Over the last four decades, vanadium compounds have been extensively studied as potential antidiabetic drugs. With the present review, we aim at presenting a general overview of the most promising compounds and the main results obtained with in vivo studies, reported from 1899–2023. The chemistry of vanadium is explored, discussing the importance of the structure and biochemistry of vanadate and the impact of its similarity with phosphate on the antidiabetic effect. The spectroscopic characterization of vanadium compounds is discussed, particularly magnetic resonance methodologies, emphasizing its relevance for understanding species activity, speciation, and interaction with biological membranes. Finally, the most relevant studies regarding the use of vanadium compounds to treat diabetes are summarized, considering both animal models and human clinical trials. An overview of the main hypotheses explaining the biological activity of these compounds is presented, particularly the most...
The impact of vanadium on endothelial dysfunction in type 2 diabetic rats: Histological insight
Introduction: The aim of this research is to investigate the effect of vanadium and or insulin on endothelial dysfunction in type 2 diabetic rats (T2DM). Material and methods:60 white albino rats were included in this research and randomly divided into 6 groups(n=10) as follows: Control group (Control): rats injected once intraperitoneally (i.p.) with citrate buffer (0.1 M, pH 4.5), vanadium treated group (Vanadium): rats received vanadyl sulfate of 0.64 mmol/kg weight freshly dissolved in 1 ml of distilled water daily through a nesophageal tube, diabetic type 2group(D type 2) : rats received high fat diet for 15 days followed by streptozotocin (25 mg/kg body weight ), diabetic type 2 and insulin group (D type 2 +I): D type 2 rats received mixtard insulin subcutaneously in a dose of 0.75 IU/100 gm weight in 0.75 ml volume once daily, diabetic type 2 and vanadium group (D type 2+V): type 2 diabetic ratsreceived the same dose of vanadium as in vanadium group after 48 h of induction of...