Selenium prevents lithium accumulation and does not disturb basic microelement homeostasis in liver and kidney of rats exposed to lithium.

INTRODUCTION: Lithium has been used in medicine for almost seventy years. Besides beneficial effects, its therapy may cause serious side-effects, with kidney and liver being the organs most vulnerable to its harmful influence. Therefore, research on protective agents against lithium toxicity has been continuing for some time. OBJECTIVE: The aim of the present study is to evaluate the influence of additional selenium supplementation on lithium content, as well as homeostasis of the essential microelements iron, zinc, copper and manganese in kidney and liver of rats undergoing lithium exposure. MATERIAL AND METHODS: The study was performed on 4 groups of male Wistar rats (6 animals each) treated with: control - saline; Li-group - Li2CO3 at a dose of 2.7 mg Li/kg b.w.; Se-group - Na2SeO3 at a dose of 0.5 mg Se/kg b.w.; Li+Se-group - both Li2CO3 and Na2SeO3 at doses of 2.7 mg Li/kg b.w. and of 0.5 mg Se/kg b.w., respectively, in the form of water solutions by stomach tube, once a day for 3 weeks. The content of the studied elements in the organ samples was determined using flame atomic absorption spectroscopy (FAAS). RESULTS: Lithium administered alone caused a significant increase in its content in liver and kidney. Additional supplementation with selenium reversed these effects, and did not markedly affect other studied microelements compared to control. CONCLUSIONS: The obtained results suggest that selenium could be regarded as an adjuvant into lithium therapy. However, considering the limitations of the present study (the short duration, using only one dose and form of selenium) the continuation of the research seems to be necessary to clarify the influence of selenium supplementation on basic microelements and lithium accumulation in organs during lithium exposure.

Lithium disturbs homeostasis of essential microelements in erythrocytes of rats: Selenium as a protective agent?

BACKGROUND: Selenium is an essential element which shows protective properties against diverse harmful factors. Lithium compounds are widely used in medicine, but, in spite of undoubted beneficial effects, treatment with these compounds may lead to severe side effects, including renal, gastrointestinal, neurological, endocrine and metabolic disorders. This study was aimed at evaluating the influence of selenium and/or lithium on lithium, iron, zinc and copper content in rats' erythrocytes as well as estimate the action of additional selenium on lithium exposure effects. METHODS: The experiment was performed on four groups of rats (six animals each): control - received saline; Li - received 2.7mg Li/kg b.w. as lithium carbonate; Se - received 0.5mg Se/kg b.w. as sodium selenite; Se+Li - received simultaneously 0.5mg Se/kg b.w. and 2.7mg Li/kg b.w. (sodium selenite and lithium carbonate). The administration was performed for three weeks, once a day by stomach tube, in form of water solutions. In erythrocytes the content of lithium, iron, zinc and copper was determined using flame atomic absorption spectroscopy. RESULTS: Lithium treatment insignificantly disturbed iron and zinc homeostasis as well as markedly increased lithium accumulation and copper content in rat erythrocytes. Selenium coadministration reversed those effects. CONCLUSIONS: The beneficial effect of selenium on disturbances of studied microelements homeostasis as well as on preventing lithium accumulation in erythrocytes in Li receiving animals allows suggesting that further research on selenium application as an adjuvant in lithium therapy is worth carrying on.

Serum Levels of Selected Vitamins and Trace Elements in Nigerian Consumers of Alcoholic Beverage: A Suggestion for DNA Hypomethylation.

Folic acid, vitamins and Zinc play essential role in DNA methylation but alcohol consumption is known to affectthe levels of these micronutrients leading to risk of developing various illnesses and certain cancers. This study determinedthe levels of DNA methylation dependent-micronutrients (folate, vitamin B12, vitamin B6, zinc and selenium) andhomocysteine as a suggestion for DNA methylation status in Nigerian alcohol consumers compared with non-consumers ofalcohol. Venous blood (5ml) was obtained from thirty-four males that consume alcoholic beverages for at least 10 years andthirty-two male controls that did not consume alcoholic beverages at least 10 years. Serum concentrations of folate, vitaminB12, vitamin B6, homocysteine (Hcy), selenium (Se) and zinc (Zn) were determined using High Performance LiquidChromatography (HPLC) and Atomic Absorption Spectrophotometry (AAS) as appropriate. Independent Student t-test wasused to compare the mean values between alcohol consumers and control. Mean differences were considered significant atp<0.05. The mean serum levels of Zn and Se were significantly raised in alcohol consumers when compared with nonalcohol consumers while the mean levels of Vitamin B6 and Hcy were significantly reduced in alcohol consumers whencompared with non-alcohol consumers. There were no statistically significant differences in the mean serum levels ofVitamin B12 and folate in alcohol consumers when compared with non-alcohol consumers. Since vitamin B6 and Hcy arerequired for DNA methylation, reduced vitamin B6 and Hcy levels in consumers of alcoholic beverages might suggest DNAhypomethylation in alcohol consumers.

Effects of aluminum chloride on some trace elements and erythrocyte osmotic fragility in rats.

Aluminum (Al) is a nonessential, toxic element to which humans are constantly exposed as a result of an increase in industrialization and improving technology practices. The aim of the study was to investigate the effects of different durations and doses of Al exposure on serum and tissue element levels and erythrocyte osmotic fragility in rats. A total of 40 male Wistar Albino rats were divided into five groups: control, group I (3 weeks, 8 mg/kg), group II (6 weeks, 8 mg/kg), group III (3 weeks, 16 mg/kg), and group IV (6 weeks, 16 mg/kg). Al chloride (AlCl3) was injected intraperitoneally (i.p.) five times a week. At the end of the experimental period, levels of Al, iron (Fe), copper (Cu), and zinc (Zn) in serum, liver, and kidney tissues were measured using inductively coupled plasma optical emission spectrometry. Osmotic fragility was determined using a spectrophotometer. The results of the experiment indicate that Al induced a statistically significant increase in Al and Fe concentrations in liver and serum as well as in Cu in the kidney. The Fe concentration in serum and kidney tissues was significantly lower in all the groups. As a result of our study, it may be concluded that tissue Al accumulation may lead to an increase in osmotic fragility of erythrocytes and abnormal trace element levels.

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.

BNIP3 up-regulation and mitochondrial dysfunction in manganese-induced neurotoxicity.

The central nervous system (CNS) appears to be the critical target of manganese (Mn), and neurotoxicity has been the focus of most of the health effects of manganese. In brain, the mechanism underlying the Mn-induced cell death is not clear. We have previously demonstrated that NFkappabeta induction and the activation of nitric oxide synthase through reactive oxygen species (ROS) represent a proximate mechanism for Mn-induced neurotoxicity. In this study, an immortalized dopaminergic cells were used to characterize the cell death signaling cascade activated by manganese. Exposure to Mn resulted in a time and concentration-related loss of cell viability as observed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and live/dead cell assay. Mn increased BNIP3 expression within 3h and continued to increase up to 24h exposure followed by a concentration-related apoptotic death as determined by TUNEL. Further, Mn treatment resulted in accumulation of reactive oxygen species and mitochondrial dysfunction with loss of mitochondrial membrane potential and release of cytochrome c. Antioxidants significantly reduced Mn-induced BNIP3 expression and attenuated cell death, demonstrating the role of oxidative stress in BNIP3 induction. Blocking BNIP3 up-regulation with a transcription or a translational inhibitor reduced the response to manganese. Cell death by manganese was reduced in the presence of CsA (PT pore inhibitor). In addition, knockdown of BNIP3 by small interfering RNA (siRNA) improved mitochondrial recovery and reduced neuronal cell loss suggesting that constitutive expression of BNIP3 plays a role in Mn-induced neurotoxicity by regulating mitochondrial functions. These findings indicate a potential detrimental role of BNIP3 in manganese-induced neuronal cell death.

Iron inhibits neurotoxicity induced by trace copper and biological reductants.

The extracellular microenvironment of the brain contains numerous biological redox agents, including ascorbate, glutathione, cysteine and homocysteine. During ischemia/reperfusion, aging or neurological disease, extracellular levels of reductants can increase dramatically owing to dysregulated homeostasis. The extracellular concentrations of transition metals such as copper and iron are also substantially elevated during aging and in some neurodegenerative disorders. Increases in the extracellular redox capacity can potentially generate neurotoxic free radicals from reduction of Cu(II) or Fe(III), resulting in neuronal cell death. To investigate this in vitro, the effects of extracellular reductants (ascorbate, glutathione, cysteine, homocysteine or methionine) on primary cortical neurons was examined. All redox agents except methionine induced widespread neuronal oxidative stress and subsequent cell death at concentrations occurring in normal conditions or during neurological insults. This neurotoxicity was totally dependent on trace Cu (>or=0.4 microM) already present in the culture medium and did not require addition of exogenous Cu. Toxicity involved generation of Cu(I) and H(2)O(2), while other trace metals did not induce toxicity. Surprisingly, administration of Fe(II) or Fe(III) (>or=2.5 microM) completely abrogated reductant-mediated neurotoxicity. The potent protective activity of Fe correlated with Fe inhibiting reductant-mediated Cu(I) and H(2)O(2) generation in cell-free assays and reduced cellular Cu uptake by neurons. This demonstrates a novel role for Fe in blocking Cu-mediated neurotoxicity in a high reducing environment. A possible pathogenic consequence for these phenomena was demonstrated by abrogation of Fe neuroprotection after pre-exposure of cultures to the Alzheimer's amyloid beta peptide (Abeta). The loss of Fe neuroprotection against reductant toxicity was greater after treatment with human Abeta1-42 than with human Abeta1-40 or rodent Abeta1-42, consistent with the central role of Abeta1-42 in Alzheimer's disease. These findings have important implications for trace biometal interactions and free radical-mediated damage during neurodegenerative illnesses such as Alzheimer's disease and old-age dementia.

Aluminium-induced anaemia in haemodialysis patients.

It appears well established that a microcytic, hypochromic anaemia is present in patients receiving regular haemodialysis treatment, who also suffer from chronic aluminium intoxication. This characteristic anaemia is slightly improved following deionization or reverse-osmosis treatment of dialysate water. Iron deficiency has been tentatively excluded as a cause of this anaemia by measurement of serum ferritin levels. The exact mechanisms involved in the pathogenesis of this anaemia are still to be fully elucidated but a disturbance in haem synthesis and porphyrin metabolism seems probable, and secondary effects of PTH in the bone marrow may be involved. Evidence has accumulated that aluminium is the most likely ion responsible for this anaemia but other ions, trace metals in excess or deficiency and potentially toxic substances cannot be excluded yet.