Trace Element Homeostasis Research Articles

Zinc and the aging brain

Alterations in trace element homeostasis could be involved in the pathology of dementia, and in particular of Alzheimer's disease (AD). Zinc is a structural or functional component of many proteins, being involved in numerous and relevant physiological functions. Zinc homeostasis is affected in the elderly, and current evidence points to alterations in the cellular and systemic distribution of zinc in AD. Although the association of zinc and other metals with AD pathology remains unclear, therapeutic approaches designed to restore trace element homeostasis are being tested in clinical trials. Not only could zinc supplementation potentially benefit individuals with AD, but zinc supplementation also improves glycemic control in the elderly suffering from diabetes mellitus. However, the findings that select genetic polymorphisms may alter an individual's zinc intake requirements should be taken into consideration when planning zinc supplementation. This review will focus on current knowledge regarding pathological and protective mechanisms involving brain zinc in AD to highlight areas where future research may enable development of new and improved therapies.

New Evidences about Adverse Health Effects Based on Chromate Environmental and Biological Exposure Assessment in Chromate Manufacturing Workers

Background Chromium (Cr) compounds are produced and applied widely. Aims On the basis of chromate exposure assessment, Cr related trace element homeostasis, DNA damage and global DNA methylation status, renal damage need further investigation. Method We recruited more than one hundred workers from chromate producing facilities as testing subjects and matched local residents without chromium exposure history served as controls. Personal sampling of airborne Cr (A-Cr) was conducted and Cr content was quantified by Flame Atomic Absorption Spectrometry. At the end of the sampling shift, blood and urine samples were collected and element concentrations were measured by inductively coupled plasma mass spectrometry and inductively coupled plasma atomic emission spectrometry. Adverse health effects including renal impairment, DNA damage, DNA methylation, and multi-trace element homeostasis were investigated comprehensively. Results 90% of the chromate production workers were exposed to A- Cr lower than 50 mu g m(-3).Chromate caused renal impairment with more severity in the tubule than glomerular. After Cr(VI) exposure, a significant increase in blood Cr, Cd, Fe, Mg, Mo, Se and Zn concentrations was observed, as well as a significant decrease in Ca concentration. Blood Cr (B-Cr) was four times higher than that of the controls, and significantly correlated with A-Cr (r = 0.568, P<0.001). Binucleated cells with micronuclei (BNMN ) frequencies were positively correlated with B-Cr and U- Cr; Ln BNMN was regressed on B-Cr, and U-Cr and A-Cr by linear models.We also found that the decreased serum folate was associated with an increased urinary 8-OhdG, DNA strand breaks and global DNA hypomethylation. Conclusions We provided some new evidences about chromate health adverse effects .Based on the above evidences and others, we therefore proposed a modified health surveillance system for chromate workers.

Effects of nanoparticle zinc oxide on emotional behavior and trace elements homeostasis in rat brain

Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain.

Effect of chromium (VI) exposure on antioxidant defense status and trace element homeostasis in acute experiment in rat

Occupational exposure to hexavalent chromium (Cr(VI)) compounds is of concern in many Cr-related industries and their surrounding environment. Cr(VI) is a proven toxin and carcinogen. The Cr(VI) compounds are easily absorbed, can diffuse across cell membranes, and have strong oxidative potential. Despite intensive studies of Cr(VI) pro-oxidative effects, limited data exist on the influence of Cr(VI) on selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx)-important components of antioxidant defense system. This study investigates the effect of Cr(VI) exposure on antioxidant defense status, with focus on these selenoenzymes, and on trace element homeostasis in an acute experiment in rat. Male Wistar rats (130-140g) were assigned to two groups of 8 animals: I. control; and II. Cr(VI) treated. The animals in Cr(VI) group were administered a single dose of K2Cr2O7 (20 mg /kg, intraperitoneally (ip)). The control group received saline solution. After 24 h, the animals were sacrificed and the liver and kidneys were examined for lipid peroxidation (LP; thiobarbituric acid reactive substances (TBARS) concentration), the level of reduced glutathione (GSH) and the activities of GPx-1, TrxR-1, and glutathione reductase (GR). Samples of tissues were also used to estimate Cr accumulation and alterations in zinc, copper, and iron levels. The acute Cr(VI) exposure caused an increase in both hepatic and renal LP (by 70%, p < 0.01 and by 15%, p < 0.05, respectively), increased hepatic GSH level and GPx-1 activity, and decreased renal GPx-1 activity. The activity of GR was not changed. A significant inhibitory effect of Cr(VI) was found on TrxR-1 activity in both the liver and the kidneys. The ability of Cr(VI) to cause TrxR inhibition could contribute to its cytotoxic effects. Further investigation of oxidative responses in different in vivo models may enable the development of strategies to protect against Cr(VI) oxidative damage.

Investigation of Zinc Concentrations in Saliva of Patients with Thyroid Diseases

Address for Correspondence/Yazisma Adresi: F. Humeyra Yerlikaya MD, University of N. Erbakan, Meram Faculty of Medicine, Department of Biochemistry, Konya, Turkey Phone: +90 332 223 77 61 E-mail: fhumeyray@hotmail.com Recevied/Gelis Tarihi: 05.06.2012 Accepted/Kabul Tarihi: 16.10.2012 Abs tract Purpose: It is well known that thyroid hormone disorders can infl uence homeostasis of trace elements in the body, such as zinc (Zn). The aim of this study was to evaluate saliva Zn levels in patients with thyroid diseases. Material and Method: The study was performed on 126 patients (21 male, 105 female) with thyroid diseases (31 hyperthyroid, 30 hypothyroid, 31 subclinical hyperthyroid and 34 subclinical hypothyroid) and 38 healthy control subjects (7 male, 31female). Saliva was collected from all participants and Zn levels were determined on an atomic absorption spectrophotometer. Results: Our results demonstrated that saliva Zn (p=0.007 for hypothyroid patients and p=0.023 for subclinical hypothyroid patients) levels were signifi cantly lower in hypothyroid and subclinical hypothyroid patients than in control subjects. Discussion: This is the fi rst study investigating saliva Zn levels in patients with thyroid diseases. Our results show that saliva Zn levels are affected by hypothyroid disease. Turk Jem 2013; 17: 1-4

The state of endogenous intoxication and the dynamics of changes of trace element homeostasis in experimental acute small bowel obstruction

The author has generalized the results of an investigation of an impaired function of the small intestine, depending on the time of the development of acute intestinal obstruction in the pathogenesis of the formation of the indicators of endogenous intoxication and trace element homeostasis in an experiment on 40 pigs of the Vietnamese breed. It has been established that the course of the disease under the experimental conditions is accompanied with essential changes of the biochemical parameters and trace elements homeostasis in the organism that were dependent on the duration of intestinal obstruction.

Effects of Iscador and Vincristine and 5-Fluorouracil on Brain, Liver, and Kidney Element Levels in Alloxan-Induced Diabetic Mice

Exposure to substance toxicity is especially dangerous for diabetics because it accelerates and intensifies diabetic complication. Homeostasis of trace elements can be disrupted by diabetes mellitus. On the other hand, disturbance in trace element status in diabetes mellitus may contribute to insulin resistance and development of diabetic complications. The aim of the present study was to compare the concentration of elements in the brain, liver, and kidneys of animals with induced diabetes after the administration of plant preparations (iscador and vincristine) and 5-fluorouracil. The experiments were carried out on male mice. The animals were divided into five groups of ten mice each: one control and four experimental groups. The first experimental group was administered alloxan at 75 mg/kg b.w. for 4 days, the second group was administered both alloxan at 75 mg/kg b.w. and vincristine 1 mg/kg b.w. for 4 days, and the third group was administered both alloxan at 75 mg/kg b.w. and 5-fluorouracil 75 mg/kg b.w. for 4 days. The animals of the fourth group were administered both alloxan at 75 mg/kg b.w. and iscador Qu at 5 mg/kg b.w. for 4 days. Calcium, magnesium, iron, copper, zinc, sodium, and potassium levels in the tissues were analyzed by flame atomic absorption spectrophotometer. We observed that zinc, copper, magnesium, sodium, and potassium were lower in the brain as compared to the control animals. The copper levels in the liver were also lower in diabetic groups than in control groups. However, the iscador and vincristine and 5-fluorouracil did not induce significant differences in the five groups. In conclusion, results of the current study indicated that changes of the investigated essential elements may contribute to explaining the role of impaired element metabolism of some elements in the progression of diabetic complications.

Zinc, Copper, Iron, and Chromium Concentrations in Young Patients with Type 2 Diabetes Mellitus

Homeostasis of trace elements can be disrupted by diabetes mellitus. On the other hand, disturbance in trace element status in diabetes mellitus may contribute to the insulin resistance and development of diabetic complications. The aim of present study was to compare the concentration of essential trace elements, zinc, copper, iron, and chromium in serum of patients who have type 2 diabetes mellitus (n = 20) with those of nondiabetic control subjects (n = 20). The serum concentrations of zinc, copper, iron, and chromium were measured by means of an atomic absorption spectrophotometer (Shimadzu AA 670, Kyoto, Japan) after acid digestion. The results of this study showed that the mean values of zinc, copper, and chromium were significantly lower in the serum of patients with diabetes as compared to the control subjects (P < 0.05). Our results show that deficiency of some essential trace elements may play a role in the development of diabetes mellitus.

Effect of benfotiamine on hepatic tissue levels of free calcium, copper, iron and zinc during CCl4-induced hepatotoxicity in rats

Background and Objectives: Toxic injury occurs in the liver more often than other organ, this can be attributed to the fact that virtually all ingested substances that are absorbed are first presented to the liver &amp; that the liver is responsible for the metabolism and elimination of many substances. Carbon tetrachloride (CCl4) is very well known to cause hepatotoxicity that may be associated with impaired calcium and trace element homeostasis. This study was designed to evaluate the protective effect of benfotiamine against CCl4-induced disturbances in calcium, iron, copper and zinc homeostasis in liver tissue of rats. Methods: Liver tissue homogenate from normal controls, CCl4-treated and benfotiamine (70 mg/kg) pre-treated before induction of hepatic damage with CCl4 in rats were obtained, and processed for estimation of levels of free forms of calcium, iron, copper and zinc using atomic absorption spectrophotometry. Results: Analysis of data revealed significant elevation in calcium, iron and copper levels in hepatic tissue due to exposure to CCl4 compared to controls, while zinc levels not significantly affected. Pretreatment with benfotiamine results in significant decrease in calcium, iron and copper levels compared to non-treated group, while zinc levels found to be significantly elevated. Conclusions: Benfotiamine has a protective effect against CCl4-induced hepatic tissue damage which may be, in part, attributed to restoration of calcium and other trace elements homeostasis.

The Toxicological Effects in Brain of Mice Following Exposure to Cerium Chloride

Cerium (Ce) compounds are now widely applied in medicine, agriculture, animal breeding, and daily life; however, the effects of Ce on human body, especially on the central nervous system, are still unclear. In order to investigate whether Ce exposure cause neurotoxicological effects, ICR mice were exposed to CeCl(3) through intragastric administration at 0, 2, 10, and 20mg/kg body weight doses everyday for 60days. The behaviors of spatial recognition memory, brain histopathology, the brain elements and neurochemicals, as well as enzymes activities in mice were determined. The Y-maze test showed that CeCl(3) exposure could significantly impair the behaviors of spatial recognition memory. Specifically, in these Ln(3+)-treated mice, the contents of Ca, Mg, Na, K, Fe, and Zn in brain were significantly altered, the activities of Na(+)/K(+)-ATPase, Ca(2+)-ATPase, Ca(2+)/Mg(2+)-ATPase, acetylcholine esterase, and nitric oxide synthase were significantly inhibited; monoamines neurotransmitters such as norepinephrine, dopamine, and 5-hydroxytryptamine were significantly decreased, while the contents of acetylcholine, glutamate, and nitric oxide were significantly increased. These results indicated that CeCl(3) exposure could impair the learning ability, which is attributed to the disturbance of the homeostasis of trace elements, enzymes, and neurotransmitter systems in the mouse brain. Therefore, our study aroused the attention of Ln application and long-term exposure effects.

Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO 2 nanoparticles

Titanium dioxide nanoparticles (TiO 2 NPs) are now in daily use including popular sunscreens, toothpastes, and cosmetics. However, the effects of TiO 2 NPs on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether TiO 2 NPs exposure results in persistent alternations in nervous system function. ICR mice were exposed to TiO 2 NPs through intragastric administration at 0, 5, 10 and 50 mg/kg body weight every day for 60 days. The Y-maze test showed that TiO 2 NPs exposure could significantly impair the behaviors of spatial recognition memory. To fully investigate the neurotoxicological consequence of TiO 2 NPs exposure, brain elements and neurochemicals were also investigated. The contents of Ca, Mg, Na, K, Fe and Zn in brain were significantly altered after TiO 2 NPs exposure. Moreover, TiO 2 NPs significantly inhibited the activities of Na +/K +-ATPase, Ca 2+-ATPase, Ca 2+/Mg 2+-ATPase, acetylcholine esterase, and nitric oxide synthase; the function of the central cholinergic system was also noticeably disturbed and the contents of some monoamines neurotransmitters such as norepinephrine, dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid, 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid were significantly decreased, while the contents of acetylcholine, glutamate, and nitric oxide were significantly increased. These first findings indicated that exposure to TiO 2 NPs could possibly impair the spatial recognition memory ability, and this deficit may be possibly attributed to the disturbance of the homeostasis of trace elements, enzymes and neurotransmitter systems in the mouse brain. Therefore, the application of TiO 2 NPs and exposure effects especially on human brain for long-term and low-dose treatment should be cautious.

The role of sulfur assimilation and sulfur-containing compounds in trace element homeostasis in plants

Sulfur assimilation and production of sulfur-containing compounds are essential biological activities that play critical roles in many biological processes, including the role of sulfur containing compounds such as glutathione and phytochelatin in trace element homeostasis in plants. This review will discuss the role of sulfur assimilation and the biosynthesis of sulfur containing compounds in both mechanisms of trace element hyperaccumulation and heavy metal stress responses in plants.

Perfect adaptation to cope with metal stress and trace element homeostasis: Metal specificity is a fundamental structural feature of snail metallothioneins

Perfect adaptation to cope with metal stress and trace element homeostasis: Metal specificity is a fundamental structural feature of snail metallothioneins

Assessment of serum macro and trace element homeostasis and the complexity of inter-element relations in bipolar mood disorders

Background Bipolar disorders are complex neuropsychiatric in nature and are clinically classified as Type I, Type II, and Type V. The etiological factors include environmental–genetic inter-relations. Trace metals play a significant role in neurological disorders. There is very limited information on the role of macro and trace elements in bipolar disorders. Methods Trace elements namely Na, K, S, Ca, Mg, P, Cu, Fe, Zn, Mn and Al were analyzed in serum samples of 3 bipolar types: bipolar I, bipolar II and bipolar V with a control group using inductively coupled plasma–atomic emission spectrometry (ICP–AES). The patients were assessed as per the standard diagnostic criteria and classified into the bipolar type I, II hypomanic, II depressives and V. Results In bipolar I (mania), Na, K, P, Cu, Al and Mn were increased significantly ( p < 0.001). In bipolar II hypomania, Na, S, Al and Mn were increased significantly ( p < 0.02), while in bipolar II depression, Na, K, Cu and Al were increased ( p < 0.001). In bipolar V, Na, Mg, P, Cu, and Al were increased significantly ( p < 0.002), though S ( p < 0.00001), Fe ( p < 0.002) and Zn ( p < 0.004) were decreased in all 3 bipolar groups. Conclusions There is a disturbance in the charge distribution and element–element interdependency in bipolar serum when compared to controls. These results suggest that there is a definite imbalance in macro and trace element homeostasis as evidenced by element inter-relationships in serum samples of bipolar groups when compared to controls.

TRACE AND NON-TRACE ELEMENTS IN BLOOD CELLS OF BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS): VARIATIONS WITH VALUES FROM LIVER FUNCTION INDICATORS

Alterations in trace and non-trace element homeostasis have been associated with both normal physiologic and pathologic processes of many species. Changes in copper and zinc, for instance, have been associated with liver disease in humans and dogs. While liver disease has been documented in marine mammals, associations of liver disease with trace and non-trace elements have not been determined. The goal of this study was to assess potential elemental associations with clinically relevant changes in liver enzymes of bottlenose dolphins (Tursiops truncatus) and to compare observed associations to what has been reported in other species. Blood cell samples were collected from 37 healthy bottlenose dolphins, maintained by the Navy Marine Mammal Program (MMP), between 1991 and 1992. Twenty-one trace and non-trace elements were assessed along with a standard liver enzyme function profile, and trace element associations to specific liver enzymes were determined. In this study, of the 21 blood cell elements assessed, 19 were measured within detectable limits in at least one of the blood samples, and 10 trace elements were found to be associated with at least one of the liver function indicators. Many of these same associations have been documented in various forms of liver disease in other species, including the associations of increases in copper and decreases in zinc with both elevated alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT). The observed analogous associations between changes in blood trace and non-trace elements and liver function indicators of bottlenose dolphins and other species may indicate similar pathologic processes and functions of some elements. Given the results of this study, additional research is warranted to further elucidate associations of trace and non-trace elements to liver disease in bottlenose dolphins.

Ytterbium and trace element distribution in brain and organic tissues of offspring rats after prenatal and postnatal exposure to ytterbium

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering the environment and eventually accumulating in the human body. Previous studies indicate that the impact of lanthanides on brain function cannot be neglected. Although neurological studies of trace elements are of paramount importance, up to now, little data are provided regarding the status of micronutritional elements in rats after prenatal and long-term exposure to lanthanide. The aim of this study is to determine the ytterbium (Yb) and trace elements distribution in brain and organic tissues of offspring rats after prenatal and long-term exposure to Yb. Wistar rats were exposed to Yb through oral administration at 0,0.1, 2, and 40 mg Yb/kg concentrations from gestation day 0 through 5 mo of age. Concentrations of Yb and other elements (Mg, Ca, Fe, Cu, Mn, and Zn) in the serum, liver, femur, and brain regions (cerebral cortex, hippocampus, cerebellum, and the rest) of offspring rats at the age of 0 d, 25 d, and 5 mo were analyzed by inductively coupled plasma-mass spectrometry. The accumulation of Yb in the brain, liver, and femur is observed; moreover, the levels of Fe, Cu, Mn, Zn, Ca, and Mg in the brain and organic tissues of offspring rats are also altered after Yb exposure. This disturbance of the homeostasis of trace elements might induce adverse effects on normal physiological functions of the brain and other organs.

Effect of Alpha-lipoic Acid Supplementation on Trace Element Levels in Serum and in Postmitotic Tissue in Aged Rats

Redistribution of redox-active divalent metal ions (e.g. copper, zinc, and iron) in postmitotic tissues of lipoic acid supplemented aging rats has been proposed to contribute to metal-catalyzed protein oxidation. DL-alpha lipoic acid (LA) (100 mg/kg body wt/day) was administered intraperitoneally to the Sprague-Dawley rats for 14 days. Serum copper levels lowered in the aged rats with LA supplementation compared to the rats without LA supplementation. On the other hand, serum zinc and iron levels increased in the aged rats with LA supplementation compared to the rats without LA supplementation. Copper levels of the postmitotic tissues were not changed in the aged rats with LA supplementation compared to the controls. The heart zinc levels detected in LA supplemented rats were significantly lower than controls. Similarly, the iron levels of the heart were found to be significantly lower in LA supplemented rats when compared to control rats. LA supplementation did not affect brain and muscle iron levels. The brain and muscle zinc levels remained the same in both group of rats. Based on the findings of our study, we have concluded that LA may exhibit prooxidant effect depending on the altered trace element homeostasis. Therefore, our results emphasize the importance of monitoring the dose of LA supplementation, duration of treatment and its potential harmful effects in the postmitotic tissues of aged rats.

Micro-chemical imaging of cesium distribution in Arabidopsis thaliana plant and its interaction with potassium and essential trace elements

Cesium as an alkali element exhibits a chemical reactivity similar to that of potassium, an essential element for plants. It has been suggested that Cs phytotoxicity might be due either to its competition with potassium to enter the plant, resulting in K starvation, or to its intracellular competition with K binding sites in cells. Such elemental interactions can be evidenced by chemical imaging, which determines the elemental distributions. In this study, the model plant Arabidopsis thaliana was exposed to 1 mM cesium in the presence (20 mM) or not of potassium. The quantitative imaging of Cs and endogenous elements (P, S, Cl, K, Ca, Mn, Fe, and Zn) was carried out using ion beam micro-chemical imaging with 5 μm spatial resolution. Chemical imaging was also evidenced by microfocused synchrotron-based X-ray fluorescence (μXRF) which presents a better lateral resolution (< 1 μm) but is not quantitative. Cesium distribution was similar to potassium which suggests that Cs can compete with K binding sites in cells. Cesium and potassium were mainly concentrated in the vascular system of stems and leaves. Cs was also found in lower concentration in leaves mesophyll/epidermis. This late representing the larger proportion in mass, mesophyll/epidermis can be considered as the major storage site for cesium in A. thaliana. Trichomes were not found to accumulate cesium. Interestingly, increased Mn, Fe, and Zn concentrations were observed in leaves at high chlorosis. Mn and Fe increased more in the mesophyll than in veins, whereas zinc increased more in veins than in the mesophyll suggesting a tissue specific interaction of Cs with these trace elements homeostasis. This study illustrates the sensitivity of ion beam microprobe and microfocused synchrotron-based X-ray fluorescence to investigate concentrations and distributions of major and trace elements in plants. It also shows the suitability of these analytical imaging techniques to complement biochemical investigations of metallic stress in plants.

Chemopreventive effect of vanadium in a rodent model of chemical hepatocarcinogenesis: reflections in oxidative DNA damage, energy-dispersive X-ray fluorescence profile and metallothionein expression

In the present study, we investigated the antitumour efficacy of vanadium in a defined rodent model of experimental hepatocarcinogenesis. Hepatic preneoplasia was induced in male Sprague-Dawley rats with a single, necrogenic, intraperitoneal injection of diethylnitrosamine (DEN) (200 mg/kg body weight) followed by promotion with phenobarbital (PB). The levels of modified DNA bases 8-hydroxy-2'-deoxyguanosine (8-OHdG), a potential marker involved in the initiation of carcinogenesis, were measured by high-performance liquid chromatography, whereas tissue trace element status and expression of metallothionein (MT), a Cu-Zn metalloprotein associated with neoplastic cell growth and subsequent development of premalignant phenotype of the cell, were studied by energy-dispersive X-ray fluorescence spectrometry and enzyme-coupled immunohistochemistry, respectively. There was a significant and steady elevation of modified bases (8-OHdG) along with substantial increase in MT immunoexpression and disturbance in trace element homeostasis following DEN exposure. Supplementation of vanadium at a dose of 0.5 ppm for four consecutive weeks strictly abated the formation of 8-OHdG (P < 0.0001; 81.28%) in preneoplastic rat liver. In a long-term DEN plus PB regimen, vanadium was able to limit in situ MT expression with a concomitant decrease in MT immunoreactivity (P < 0.05). Furthermore, vanadium treatment throughout the study restored hepatic levels of essential trace elements and decreased nodular incidence (58.34%) and nodule multiplicity (P < 0.001; 66.89%) in rats treated with DEN plus PB. Taken together, the study provides evidence in support of the chemopreventive potential of vanadium in limiting neoplastic transformation during the preneoplastic stages of hepatocarcinogenesis in rats.

Neurotoxicological consequence of long-term exposure to lanthanum

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering into the environment and eventually accumulated in human body. Recently, a new medicine, lanthanum carbonate (Fosrenol), has been used to treat chronic renal failure (CRF), and the dosage is much higher than the daily intake of lanthanides. However, the effects of lanthanides on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether long-term lanthanum exposure results in persistent alternations in nervous system function. Wistar rats were exposed to lanthanum chloride (LaCl 3) through oral administration at 0, 0.1, 2 and 40 mg/kg concentration from 4 weeks through 6 months of age. Morris water maze test showed that lanthanum exposure at 40 mg/kg could significantly impair the behavioral performance. To fully investigate the neurotoxicological consequence of lanthanum exposure, brain elemental distributions and neurochemicals were also investigated. The distributions of brain elements such as Ca, Fe and Zn were significantly altered after lanthanum exposure. Moreover, 40 mg/kg LaCl 3 significantly inhibited the activity of Ca 2+-ATPase; the function of the central cholinergic system was also noticeably disturbed and the contents of some monoamines neurotransmitters were significantly decreased. These findings indicate that chronic exposure to lanthanum could possibly impair the learning ability and this deficit may be possibly attributed to the disturbance of the homeostasis of trace elements, enzymes and neurotransmitter systems in brain. Therefore, the application of lanthanide, especially in pharmacology, should be cautious.