Effect of dietary copper on vanadate toxicity in chicks

The addition of copper to a corn-soybean diet at levels of 200 mg/kg and above lessened the growth-retarding effect of vanadate for chicks. This interaction between vanadate and copper was evident in bothad libitum-fed chicks and chicks in which feed consumption was restricted to approximately equal amounts. The ameliorating effect of copper was not accompanied by changes in the femur levels of vanadium nor by changes in the hepatic or renal glutathione concentrations. Zinc added at 515 mg/kg of diet had no effect on the toxicity of vanadium. Sodium sulfate added at a level to supply the same amount of sulfate, as supplied by 500 mg/kg copper sulfate, was without effect on the vanadate-induced growth depression. The underlying mechanism of the interaction of copper and vanadium is not known, but it does not lie in changes in feed consumption or organ burdens of vanadium, as represented by the femur vanadium concentrations.     

Methyl mercury toxicity in the chick embryo

The toxicity of methyl mercury (mHg) in the developing chick embryo was investigated. The relationship of dose, time of administration (i.e., days 4-9 of development), and body levels of mercury was examined. The LD50 for mHg injected into the yolk sac on day 5 of incubation was 40-50 micrograms. Embryos dying within 24 hours showed increased total body mHg levels when compared to survivors (219 +/- 67 vs. 105 +/- 41 micrograms/gm, mean +/- SD). Absorption was dose-related, with a good correlation between mortality and body, blood, and brain levels. Daily analysis of body mHg levels after injection on day 5 showed continued mHg accumulation (0.88 +/- 0.35 micrograms/embryo/day). However, the rate of embryo growth exceeded the rate of mHg absorption, resulting in a progressive decrease in mHg in concentration in tissues (from 94.5 +/- 34.2 micrograms/gm on day 6 to 45.3 +/- 13.4 on day 9). Administration after day 5 resulted in a significant reduction in levels of mHg in the brain on day 18 (from 11.4 +/- 2.1 micrograms/gm when given on day 5 to 8.4 +/- 2.3 when given on day 9) and in mortality (from 64% to 33%). Because blood mHg levels remained unchanged, the increased brain levels and higher mortality early in embryogenesis may reflect facilitated transfer of mHg across a poorly developed blood-brain barrier. Later in development, the reduced mortality and lower brain mHg levels correspond to the formation of specialized interendothelial junctions and a more effective blood-brain barrier.     

环境汞污染对藻类的毒性效应及其影响因素

综述了汞污染对藻类的毒性效应及影响因素。水环境中汞主要以元素汞、无机汞和有机汞3种形式存在。藻类吸附汞主要分为胞外的快速吸附和胞内的缓慢富集,在安全浓度内,金属汞对藻生长有一定的促进作用,随着浓度增大,抑制藻生长或致死。汞进入藻体细胞后,藻类为了存活会产生一系列保护机制。藻类对汞的排斥和排出作用可能就是对汞耐性的一种重要机制。藻类也可以通过多种方式减少汞进入藻类细胞,以及通过与其他物质结合汞使其排出胞外。温度、pH、生物学因素等影响重金属对藻类的毒性作用。并就藻类对汞耐性和适应机理、利用藻类修复和监测重金属污染、藻类响应汞胁迫的信号转导途径及其保护机制等未来研究领域进行了展望。     

The effect of vanadate on proton-sucrose cotransport in ricinus cotyledons

The effects of orthovanadate on the uptake of sucrose by Ricinus cotyledons and on sucrose-coupled proton influx were measured in order to gain insight into the relationship to the plasma membrane proton pump. Vanadate had no effect on short-term sucrose uptake. In longterm experiments (>30 min) sucrose uptake was progressively inhibited, but only at high external sucrose concentrations. Vanadate did not affect proton efflux pumping in the absence of sucrose and neither did it change the initial rate of sucrose-coupled proton influx. However, it enhanced the maximal level of sucrose-induced alkalinization of the medium at all sucrose concentrations tested. This is interpreted as an inhibiting effect of vanadate on the proton pump that recycles protons during sucrose-proton cotransport. The sensitivity towards vanadate indicates that this proton pump is an ATPase. A second proton-translocating system, that is insensitive to vanadate, is postulated to function in the absence of sucrose.     

Sodium vanadate toxicity in adult and developing rats

The toxic effect of vanadium (sodium metavanadate) during pregnancy and lactation was studied by feeding vanadium to pregnant, Sprague-Dawley rats at levels of 1 (control) or 75 μg V/g diet through d 21 postpartum, at which time they were killed. Vanadium-fed dams had lower food intakes and weight gains than controls during pregnancy. Survival until d 21 postpartum was significantly lower in the vanadium pups compared to controls. In addition, the surviving pups gained less weight than control pups, despite similar birth weights. On a relative body weight basis, vanadium pups had larger livers, brains, and testes than controls, suggesting that these animals were developmentally delayed. Vanadium dams and pups had higher concentrations of hepatic vanadium than controls. Vanadium pups also had higher concentrations of hepatic zinc than control pups. Maternal hepatic zinc concentrations were not affected by diet. Also, no significant differences in hepatic iron, copper, or manganese concentrations were observed for either dams or pups. Hepatic thiobarbituric acid reactivity was higher in whole cell and isolated mitochondria for vanadium dams and pups than for control dams and pups, indicating that these animals may have had higher levels of lipid peroxidation. This idea was supported by the observation of lower concentrations of reduced glutathione in the livers of vanadium pups compared to controls. In contrast, kidney and brain glutathione levels were not affected by diet. In conclusion, animals during periods of rapid growth are susceptible to vanadium toxicity, and increased lipid peroxidation may be one factor underlying this toxicity.     

The effect of antioxidant-deficiency on phospholipid composition in the chick brain

Abstract— A significant increase in arachidonate was noted in the total phospholipids of brain of chicks with nutritional antioxidant-deficiency and encephalomalacia. After thin-layer chromatography of the brain lipids, this increase in arachidonate was found to be restricted to the phosphatidyl serine fraction. Significant decreases in docosahexaenoate and docosapentaenoate were noted in the phosphatidyl ethanolamine fraction. The changes in fatty acid composition of phospholipids in chick brain are comparable to those previously observed in phospholipids of skeletal muscle, liver and testes of the rat.     

The effect of vanadate on glucose transport and metabolism in rat small intestine

The effect of sodium orthovanadate on the absorption, transmural transport and metabolism of glucose was studied by perfusion of isolated loops of rat jejunum in vitro. The presence of 1 mM vanadate in the serosal medium diminished absorption from 539 +/- 19 (n = 12) to 246 +/- 19 (P less than 0.001) mumol/h per g dry weight and transmural transport from 333 +/- 17 to 14 +/- 19 (P less than 0.001) mumol/h per g dry weight, whereas glucose utilisation was unaffected. The rate of release of lactate into the serosal medium was also diminished from 168 +/- 14 to 75 +/- 5 mumol/h per g dry weight (P less than 0.001). The observed rates were linear with respect to time and vanadate was effective within 5 min. In contrast, the rate of release of lactate into the luminal perfusate was strongly enhanced. Moreover, the progress curve showed a positive transient with an apparent lag time of 18.0 +/- 0.3 min, during which the rate increased to a value 9.2-times that of the control. Under the final steady-state conditions, the ratio of mucosal to serosal lactate production was 5.2 +/- 0.2 compared with 0.25 +/- 0.06 for the control, so that the effect of vanadate was to reverse the vectorial disposition of lactate. The concentration dependence of the effect of vanadate on absorption and metabolism was similar to that observed for the inhibition by vanadate of Na+/K+-ATPase activity in mucosal homogenates. The results are discussed in terms of the dissipation of transmembrane Na+ gradients as a result of the inhibition of the Na+/K+-ATPase.     

Effect of dietary fluoride on selenite toxicity in the rat

Three factorial experiments were conducted to determine if high dietary fluoride (F) would inhibit selenite toxicity in rats. Initially, three levels of selenite (0.05, 3, and 5 mg/kg diet) were matched against three levels of F (2, 75, and 150 mg/kg diet). Fluoride failed to prevent the depressive effect of selenite on 8-wk food intake and body wt gain. Selenium (Se) concentration of plasma and kidney and enzymatic activity of whole blood glutathione peroxidase (GSH-Px) were also unaffected by F. Liver Se concentration, however, was slightly (12%) but significantly (p<0.025) reduced when the highest F and Se levels were combined. Fluoride (150 mg/kg) appeared to reduce liver selenite toxicity (5 mg/kg). Therefore, further study focused on liver histology with treatments that eliminated the middle levels of selenite and F. Fluoride prevented the hepatic necrosis seen in selenite-toxic rats. Similar histological lesions were not observed for kidney or heart. Fluoride partially (26%) but significantly (p<0.025) reduced thiobarbituric-reactive substances in selenite-toxic rats, but there was no F effect on intracellular distribution of liver Se, glutathione levels in liver and kidney, or on liver xanthine oxidase activity. Overall, the protective effect of F on selenite toxicity appears to be confined to liver pathology. The exact mechanism for this effect, however, remains unclear. Oregon Agricultural Experiment Station Technical Paper No. 9728.     

The effect of graded hypoxia on the embryonic chick heart

Embryonic ventricular function in the chick was measured in response to graded levels of hypoxia. Myocardial contractility, as measured by cinephotoanalysis and expressed as shortening fraction, was significantly depressed after 1 hour of moderate hypoxia (6% O2) and after 5 hours of milder (16% O2 and 11% O2) levels of hypoxia (P less than .05). Microscopy confirmed associated myocyte damage with cell death noted after 5 hours of moderate hypoxic stress. Heart rate change was not related to the severity of hypoxia. The greatest level of tachycardia was noted with conditions of mildest hypoxia (16% O2). The data confirm that cardiac contractility, as measured by shortening fraction, is depressed on exposure to hypoxia, with impairment of function related to the severity of the hypoxic conditions.     

The time sequence of adaptive changes to dietary phosphorus deficiency in the chick

Ten-day old chicks were divided into 6 groups which were fed a low phosphorus (P) diet for periods of 0, 0.5, 1, 3, 7 or 11 days before killing at 3 weeks old. Labelled calcium (47Ca) was injected intraperitoneally into some birds 18 hours before killing. A marked fall in growth rate, plasma phosphorus level, plasma growth hormone level and renal 24-hydroxylase activity levels had occurred by 12 hours after the experimental diet had started. After one day on the diet, the rate of duodenal Ca absorption had risen and continued to rise up to the 11th day. During this period, the renal 25-hydroxyvitamin D-1-hydroxylase activity rose slightly while the 24-hydroxylase activity rose towards the control level. At 24 hours, the 47Ca level in the bone was markedly lower than in the control group and remained low. It was concluded that the first adaptive response of the chick to dietary P insufficiency was to suppress growth. Subsequent adaptive responses were to increase the rate of Ca and P absorption from the gut and mobilisation from the bone but despite these measures, the growth rate only recovered slightly and the plasma P level continued to fall.     

The effect of oxidized isoprenaline on the chick embryonic heart

Intra-amnial administration of isoprenaline (IPRO) to chick embryos induces a number of myocardial lesions. The purpose of the present study was to investigate whether similar changes may also be induced after injection of spontaneously oxidized isoprenaline and commercially obtained adrenochrome. Cardiotoxicity of these substances has been demonstrated in adult animals. IPRO, oxidized IPRO, or adrenochrome were administered intra-amnially to 10-day-old chick embryos at doses of 0.1, 1.0, 10.0, and 100.0 mg X kg-1. Parallel experimental groups received propranolol at a dose of 1 mg X kg-1, 15 s before injection of IPRO or oxidized IPRO. The cAMP level in the heart was determined by radioimmunoassay 2 and 30 min after administration of IPRO, oxidized IPRO, or adrenochrome at a single dose of 10.0 mg X kg-1. It has been found that in embryos the effect of IPRO and oxidized IPRO is dose dependent. The rise in mortality and development of cardiomegaly together with increased hydration and disturbances of the development of coronary vascularization were highly significant starting from the dose of 10 mg X kg-1. Furthermore, both drugs significantly increased cAMP levels in the embryonic heart. On the other hand, the administration of adrenochrome was without any effect. The changes induced by IPRO were prevented by the administration of the beta-blocking agent propranolol; the lesions induced by spontaneously oxidized IPRO were, however, prevented only partially.     

The effect of vanadate on receptor-mediated endocytosis of asialoorosomucoid in rat liver parenchymal cells

Vanadate is a phosphate analogue that inhibits enzymes involved in phosphate release and transfer reactions (Simons, T. J. B. (1979) Nature 281, 337-338). Since such reactions may play important roles in endocytosis, we studied the effects of vanadate on various steps in receptor-mediated endocytosis of asialoorosomucoid labeled with 125I-tyramine-cellobiose (125I-TC-AOM). The labeled degradation products formed from 125I-TC-AOM are trapped in the lysosomes and may therefore serve as lysosomal markers in subcellular fractionation studies. Vanadate reduced the amount of active surface asialoglycoprotein receptors approximately 70%, but had no effect on the rate of internalization and retroendocytosis of ligand. The amount of surface asialoglycoprotein receptors can be reduced by lowering the incubation temperature gradually from 37 to 15 degrees C (Weigel, P. H., and Oka, J. A. (1983) J. Biol. Chem. 258, 5089-5094); vanadate affected only the temperature--sensitive receptors. Vanadate inhibited degradation of 125I-TC-AOM 70-80%. Degradation was much more sensitive to vanadate than binding; half-maximal effects were seen at approximately 1 mM vanadate for binding and approximately 0.1 mM vanadate for degradation. By subcellular fractionation in sucrose and Nycodenz gradients, it was shown that vanadate completely prevented the transfer of 125I-TC-AOM from endosomes to lysosomes. Therefore, the inhibition of degradation by vanadate was indirect; in the presence of vanadate, ligand did not gain access to the lysosomes. The limited degradation in the presence of vanadate took place in a prelysosomal compartment. Vanadate did not affect cell viability and ATP content.     

The mitogen-activated protein kinase pathway contributes to vanadate toxicity in vascular smooth muscle cells

Vanadate has been considered in the treatment of diabetes because of its insulin-like effects. However, it has severe toxic effects in both animal and man. In cultured cells, vanadate can either cause death or be growth stimulatory, depending on the cell type and growth conditions. Here, we report that in baboon aortic smooth muscle cells (SMCs), vanadate induced p42/p44 mitogen-activated protein kinase (MAPK) activity. This effect was abolished in the presence of the specific MAPK kinase (MAPKK) inhibitor PD098059. Although activation of p42/p44^MAPK/MAPKK is generally thought to be necessary for proliferation, in SMCs, vanadate did not promote DNA synthesis and inhibited thymidine incorporation stimulated by platelet-derived growth factor (PDGF)-BB in a dose dependent fashion (IC₅₀: 30 M). Prolonged exposure to vanadate exerted cytotoxic effects. Cells retracted, rounded up and detached from the substratum. These vanadate-induced morphological changes were blocked in the presence of PD098059. The addition of PDGF-BB further activated p42/p44^MAPK/MAPKK in the presence of vanadate and substantially increased vanadate toxicity. We conclude from these observations that activation of the p42/p44^MAPK/MAPKK signalling module contributes to the cytotoxic effects induced by vanadate.