Macrophage activation by a vanadyl-aspirin complex is dependent on L-type calcium channel and the generation of nitric oxide

Bone homeostasis is the result of a tight balance between bone resorption and bone formation where macrophage activation is believed to contribute to bone resorption. We have previously shown that a vanadyl(IV)–aspirin complex (VOAspi) regulates cell proliferation and differentiation of osteoblasts in culture. In this study, we assessed VOAspi and VO effects and their possible mechanism of action on a mouse macrophage cell line RAW 264.7. Both vanadium compounds inhibited cell proliferation in a dose-dependent manner. Nifedipine completely reversed the VOAspi-induced macrophage cytotoxicity, while it could not block the effect of VO. VOAspi also stimulated nitric oxide (NO) production, the oxidation of dihydrorhodamine 123 (DHR-123) and enhanced the expression of both constitutive and inducible isoforms of nitric oxide syntases (NOS). All these effects were abolished by nifedipine. Althogether our finding give evidence that VOAspi-induced macrophage cytotoxicity is dependent on L-type calcium channel and the generation of NO though the induction of eNOS and iNOS. Contrary, the parent compound VO exerted a cytotoxic effect by mechanisms independent of a calcium entry and the NO/NOS activation.     

决明子生芽转化有机钒的效果研究

目的 探讨决明子生芽转化有机钒的效果.方法 利用透析方法 将富钒决明子芽中的有机钒和无机钒分离,用石墨炉原子吸收分光光度法测定富钒决明子芽中的总钒含量和无机钒含量,计算决明子芽的有机钒转化率.结果 决明子芽在自然生长过程中,种皮能够从环境中富积大量的无机钒,但钒的有机转化过程主要发生在种皮内.结论 决明子生芽是钒的生物有机化途径之一.     

CD11c decrease in mouse thymic dendritic cells after vanadium inhalation

Vanadium (V) is a transition metal found in air adsorbed onto suspended particles. As a result, urban populations are often exposed to this element as a constituent of particulate matter (PM). One aspect of the myriad toxicities that might arise from these exposures is altered immune responses. Previous reports from the laboratory reported modifications in splenic architecture – with germinal center hyperplasia and a suppressed humoral immune response – in mice that had been exposed to vanadium agents via inhalation. This paper reports a decrease in the presence of the CD11c surface marker on mouse thymic dendritic cells (DC) as a result of host exposure to vanadium (here, in the form of vanadium pentoxide; V₂O₅) over a period of 4 weeks. All results were obtained using immunohistochemistry and flow cytometry. It is surmised that this decrease might induce a dysfunction, including possible negative selection of T-cells, which could increase the presence of autoreactive clones in the exposed host. Such an outcome could, in turn, increase the risk for development of autoimmune reactions in different organs specifically, and of autoimmune diseases in general in these V-exposed hosts.     

联麦氧钒对糖尿病大鼠心肌脂蛋白脂酶mRNA表达的影响

目的　探讨糖尿病大鼠应用联麦氧钒 (BMOV)心肌脂蛋白脂酶 m RNA表达的变化规律。方法　采用逆转录聚合酶链式反应的方法。观察 BMOV治疗前后糖尿病大鼠心肌细胞脂蛋白脂酶 m RNA水平的变化。结果　糖尿病大鼠心肌脂蛋白脂酶 m RNA是升高的 ,经 BMOV治疗后心肌细胞脂蛋白脂酶 m RNA表达可降低 ,基本恢复到正常对照水平。结论　 BMOV可恢复糖尿病大鼠心肌细胞升高的脂蛋白脂酶 m RNA表达 ,调整脂代谢 ,改善心肌细胞能量物质的供给及利用。     

Biochemical and ultrastructural changes in kidney and liver of African Giant Rats (Cricetomysgambianus,Waterhouse, 1840) exposed to intraperitoneal sodium metavanadate (vanadium) intoxication

We studied the hepatic and renal impact of sodium metavanadate (SMV) exposure in African giant rats (AGR). Twelve male AGR were used and divided into two groups. The control group received sterile water while the SMV-exposed group received 3 mg/kg SMV intraperitoneally for 14 days. SMV exposed AGR groups showed significantly decreased activities of serum AST, ALT, ALP and creatinine concentration but increased blood urea nitrogen (BUN), albumin and globulin concentrations. Kidney ultrastructure examination revealed atrophy of the glomerular tuft, loss of podocytes, distortions of the endothelium and glomerular basement membrane. The liver sinusoids fenestration phenotypes were abnormal. Hepatocytes exhibited hypertrophy with uneven, crenated and dentate nuclei. SMV exposure induced activation of monocytes, as well as Kupffer and fibrous cells. Alterations in glomerular podocytes and cell-cell and cell matrix contact and inflammatory liver fibrosis are key events in progressive glomerular failure and hepatic damage due to SMV intoxication.     

溶栓疗法对急性心肌梗死患者血清中铬钴镍钒钼含量变化的研究

对34例急性心肌梗死患者,给予溶栓治疗.测定其血清中必需微量元素的含量.结果显示患者治疗前血清中铬、钴、镍、钒、钼的含量均降低,与对照组比较,二者有高度显著性差异,P＜0.01;治疗后血清镍和钒的含量出现升高,与治疗前比较,二者差异有显著性或有高度显著性,P＜0.05或P＜0.01.钴的含量比治疗前进一步下降.但铬和钼的含量,治疗前后无显著性差异(P＞0.05).     

钒对实验性糖尿病小鼠胰岛影响的免疫组织化学观察

钒系人体必需微量元素，其生物学作用比较复杂。给实验性糖尿病小鼠口服钒酸盐，１个月后对小鼠胰腺进行了ＰＰＡ法免疫组织化学观察。结果，钒对糖尿病小鼠胰岛形态结构的恢复（改善）有积极的影响。     

Tyrosine phosphatase inhibitors combined with retinoic acid can enhance differentiation of neuroblastoma cells and trigger ERK- and AKT-dependent,p53-independent senescence

Retinoic acid (RA)-induced differentiation therapy is partially successful in neuroblastoma treatment. We found that a novel combination of vanadium-based PTP inhibitors with RA induced extensive differentiation in neuroblastoma cells. In contrast to RA alone, this led to either permanent differentiation or senescence after 14 days of combined treatment followed by chemical removal. Senescence was dependent in part on synergistic AKT and ERK activation. p21 was also strongly induced, but in contrast to oncogene-induced senescence, p53 was not activated. Vanadium-based inhibitors thus serve strongly to enhance RA’s ability to drive differentiation and a novel form of senescence in neuroblastoma cells.     

Vanadium compounds induce stronger growth suppression in PTEN-deficient prostate cancer cells by ROS-mediated mechanism

In the present study, we investigated the antiproliferative effect and the underlying mechanism of three antidiabetic vanadium compounds, metavanadate, VO(acac)₂ and VO(ma)₂, in human prostate cancer cells (PC-3 and DU-145). The results showed that vanadium compounds caused cell cycle arrest at G2/M phase evidenced by the elevation of phosphorylated Cdc2 at tyr-15. Moreover, the results revealed that vanadium compounds induced reactive oxygen species (ROS) elevation in the two cell lines. The decreased level of Cdc25C could be rescued by the antioxidant, N-acetylcysteine, indicating that vanadium compounds-induced G2/M arrest was mediated by ROS. Additionally, the three vanadium compounds exerted more potent growth inhibitory effect on PC-3 cells which are PTEN-deficient and with higher level of basal ROS. It suggested that PTEN protein might serve as a biomarker for the selectivity of antitumor therapy using ROS-generating agents. Since the studied vanadium compounds have been shown the antidiabetic activities in the previous studies, there may be additional benefits in the potential application of vanadium compounds to suppress the growth of prostate cancer cells.     

The long-term toxicity and hypoglycemic effect of vanadyl complexes on non-diabetic and type II diabetic mice

Vanadium compounds are promising anti-diabetic agents. However, the concern in the toxicity, especially the long-term renal side effectalong with diabetic status,is restricting the further development of this metal drug. Recently, we have prepared a bis((5-hydroxy-4-oxo-4H-pyran-2-yl) methyl 2-hydroxy-benzoatato) oxovanadium (BSOV), which exhibited excellent hypoglycemic effect with low acute toxicity. In order to facilitate the development of anti-diabetic vanadium complexes, especially BSOV, we studied the long-term toxicity and hypoglycemic effect of BSOV in comparison with bis(maltolato)oxovanadium (BMOV) on both non-diabetic and type II diabetic mice. The experiments confirmed a stable hypoglycemic effect for both the vanadium complexes over the testing period (6–7 months). However, the chronic administration of vanadium compounds slightly increased oxidative stress in ICR mice and the induced renal interstitial edema (RIE) in a part of the diabetic animals associated with low levels of serum albumin. The use of an antioxidant dietary supplement (a combination of vitamin C and Zinc gluconate) could prevent vanadium-induced oxidative stress but have marginal effect on RIE. However, BSOV caused much lower incidence of RIE than BMOV did, suggesting that BSOV is an important step towards the successful development of anti-diabetic vanadium drugs.