RESUMO
Vanadium compounds have been primarily investigated as potential therapeutic agents for the treatment of various major health issues, including cancer, atherosclerosis, and diabetes. The translation of vanadium-based compounds into clinical trials and ultimately into disease treatments remains hampered by the absence of a basic pharmacological and metabolic comprehension of such compounds. In this review, we examine the development of vanadium-containing compounds in biological systems regarding the role of the physiological environment, dosage, intracellular interactions, metabolic transformations, modulation of signaling pathways, toxicology, and transport and tissue distribution as well as therapeutic implications. From our point of view, the toxicological and pharmacological aspects in animal models and humans are not understood completely, and thus, we introduced them in a physiological environment and dosage context. Different transport proteins in blood plasma and mechanistic transport determinants are discussed. Furthermore, an overview of different vanadium species and the role of physiological factors (i.e., pH, redox conditions, concentration, and so on) are considered. Mechanistic specifications about different signaling pathways are discussed, particularly the phosphatases and kinases that are modulated dynamically by vanadium compounds because until now, the focus only has been on protein tyrosine phosphatase 1B as a vanadium target. Particular emphasis is laid on the therapeutic ability of vanadium-based compounds and their role for the treatment of diabetes mellitus, specifically on that of vanadate- and polioxovanadate-containing compounds. We aim at shedding light on the prevailing gaps between primary scientific data and information from animal models and human studies.
Assuntos
Diabetes Mellitus/metabolismo , Hipoglicemiantes/uso terapêutico , Compostos de Vanádio/uso terapêutico , Vanádio/química , Vanádio/farmacologia , Animais , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipoglicemiantes/química , Vanádio/sangue , Compostos de Vanádio/químicaRESUMO
This study examined changes in the metabolism of magnesium (Mg), and related serum parameters, following treatment with vanadium (V) in streptozotocin-diabetic rats. Over a period of five weeks, four groups were examined: control, diabetic, diabetic-treated with 1 mg V/day or 3 mg V/day. The V was supplied in drinking water as bis(maltolato)oxovanadium(IV). The Mg levels were measured in food, faeces, urine, serum, muscle, kidney, liver, spleen, heart and femur. Albumin, uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides, aspartate-aminotransferase and alkaline-phosphatase were determined in serum. In the diabetic group, Mg retained and Mg content in serum and femur decreased, while levels of uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides and alkaline-phosphatase and aspartate-aminotransferase activity increased compared with control rats. In the diabetic group treated with 1 mg V/day, Mg retained, serum levels of Mg, urea and triglycerides, and alkaline-phosphatase activity remained unchanged, while levels of uric acid, total-cholesterol and LDL-cholesterol increased and the Mg content in femur and aspartate-aminotransferase activity decreased compared with the diabetic untreated group. In the diabetic rats treated with 3 mg V/day, food intake and glycaemia were normal. In this group, Mg content in serum, kidney and femur, levels of urea and aspartate-aminotransferase and alkaline-phosphatase activity decreased, whereas LDL-cholesterol increased, uric acid and total-cholesterol levels remained unchanged in comparison with untreated diabetic rats. In conclusion, although treatment with 3 mg V/day normalised the glycaemia, the hypomagnesaemia and tissue depletion of Mg seen in the diabetic rats, caused by the treatment with V, could have partially contributed to the fact that V did not normalise other serum parameters altered by the diabetes.
Assuntos
Diabetes Mellitus Experimental/complicações , Deficiência de Magnésio/complicações , Vanádio/efeitos adversos , Animais , Diabetes Mellitus Experimental/sangue , Magnésio/sangue , Deficiência de Magnésio/sangue , Masculino , Especificidade de Órgãos/efeitos dos fármacos , Ratos , Ratos Wistar , Estreptozocina , Vanádio/sangueRESUMO
The trace element vanadium, has been studied during the past few years, however is unknown its cellular actions. This paper intends to give a review of the different vanadium routes, its absorption, distribution, metabolism and biotransformation, mainly because vanadium use has increased in the petroleum and steel industries affecting their workers for its toxic effects.
Assuntos
Vanádio/metabolismo , Adulto , Animais , Biotransformação , Calorimetria , Dieta , Feminino , Humanos , Masculino , Análise de Ativação de Nêutrons , Coelhos , Ratos , Absorção Cutânea , Espectrometria por Raios X , Espectrofotometria , Análise Espectral , Vanádio/análise , Vanádio/sangueRESUMO
The present study describes the relationship between the whole blood Pb, plasma Al and plasma V levels and the arterial hypertension, for four groups of individuals: 20 normotensive azotemic patients in periodic hemodialysis (CRF), 20 hypertensive azotemic patients in periodic hemodialysis (CRF-AHT), 20 individuals with severe essential hypertension and normal renal function (AHT) and 20 individuals with normal renal function and normal blood pressure (controls) evaluated during a period of 1 year. The renal population's blood Pb was comparable with that found in the non-renal groups. Blood Pb in the essential AHT was higher than in controls (P < 0.05). CRF and CRF-AHT showed higher Al levels than those individuals with normal renal function (P < 0.01). In CRF, plasma Al did not correlate with the arterial hypertension. Plasma Al was increased in the AHT individuals (P < 0.05) with respect to the control group, suggesting the possible influence of this metal in the appearance of the arterial hypertension. In this study, the CRF-AHT patients had plasma V statistically higher (P < 0.005) than controls. However, no differences were found between plasma V of CRF and CRF-AHT groups or between AHT and controls. These results suggest that V in AHT is of doubtful significance, except maybe when the renal failure and the arterial hypertension appear together. In summary, high levels of blood Pb and plasma Al are associated with arterial hypertension in individuals without renal disease. Higher plasma V levels were not found in hypertensives with normal renal function with respect to controls.
Assuntos
Alumínio/sangue , Hipertensão/sangue , Chumbo/sangue , Vanádio/sangue , Pressão Sanguínea , Creatinina/sangue , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Valores de Referência , Diálise Renal , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria Atômica/métodos , Uremia/sangue , Uremia/complicaçõesRESUMO
Bone accumulation of metals, other than aluminum (Al), in patients with chronic renal failure (CRF) has rarely been studied. We report the bone and blood levels of iron (Fe), vanadium (V), lead (Pb), Al and calcium (Ca) in 18 CRF patients on long-term hemodialysis and in 14 controls (C). Significant increments in mean blood Al (1,300%), V (160%) and Fe (60%) and decrease in blood Pb (-50%) were found in the patients with CRF. Renal subjects had higher bone concentrations (mean +/- S.E.M.; microgram/g of bone) of Al (CRF = 129.1 +/- 16.9; C = 12.6 +/- 2.9; P < 0.0001), Fe (CRF = 940.4 +/- 133.4; C = 263.4 +/- 49.0; P < 0.0001) and V (CRF = 2.55 +/- 0.43; C = 1.39 +/- 0.36; P = 0.0308) and lower Ca (CRF = 268.2 +/- 11.1 mg/g; C = 377.2 +/- 28.1; P = 0.0017). A positive correlation was found between bone Al and V (r = 0.355, P < 0.05). Results indicated that a significant bone accumulation of Al, Fe and V, but not Pb, occurred in the hemodialyzed azotemic individuals.