Emerging Topics in Metal Complexes: Pharmacological Activity.

This Special Issue (SI), "Emerging Topics in Metal Complexes: Pharmacological Activity", includes reports updating our knowledge on metals with multidirectional biological properties and metal-containing compounds/complexes for their potential therapeutic applications, with a focus on strategies improving their pharmacological features [...].

CNS-Related Effects Caused by Vanadium at Realistic Exposure Levels in Humans: A Comprehensive Overview Supplemented with Selected Animal Studies.

Neurodegenerative disorders, which are currently incurable diseases of the nervous system, are a constantly growing social concern. They are progressive and lead to gradual degeneration and/or death of nerve cells, resulting in cognitive deterioration or impaired motor functions. New therapies that would ensure better treatment results and contribute to a significant slowdown in the progression of neurodegenerative syndromes are constantly being sought. Vanadium (V), which is an element with a wide range of impacts on the mammalian organism, is at the forefront among the different metals studied for their potential therapeutic use. On the other hand, it is a well-known environmental and occupational pollutant and can exert adverse effects on human health. As a strong pro-oxidant, it can generate oxidative stress involved in neurodegeneration. Although the detrimental effects of vanadium on the CNS are relatively well recognized, the role of this metal in the pathophysiology of various neurological disorders, at realistic exposure levels in humans, is not yet well characterized. Hence, the main goal of this review is to summarize data on the neurological side effects/neurobehavioral alterations in humans, in relation to vanadium exposure, with the focus on the levels of this metal in biological fluids/brain tissues of subjects with some neurodegenerative syndromes. Data collected in the present review indicate that vanadium cannot be excluded as a factor playing a pivotal role in the etiopathogenesis of neurodegenerative illnesses, and point to the need for additional extensive epidemiological studies that will provide more evidence supporting the relationship between vanadium exposure and neurodegeneration in humans. Simultaneously, the reviewed data, clearly showing the environmental impact of vanadium on health, suggest that more attention should be paid to chronic diseases related to vanadium and to the assessment of the dose-response relationship.

In vitro effect of vanadyl sulfate on cultured primary astrocytes: cell viability and oxidative stress markers.

Exposure to vanadium has been associated with deleterious effects on the central nervous system in animals and humans. Although vanadium-derived pro-oxidant species were reported to be involved in vanadium-mediated neurotoxicity, the ability of this metal to induce oxidative stress markers in glial cells remains to be elucidated. In this study, we investigated the cytotoxicity and the generation of reactive oxygen species (ROS) and nitric oxide (NO) by mouse primary astrocytes after treatment with vanadyl sulfate (VOSO4 ) at concentrations of 20, 50, 100, 200, and 500 µM. The resazurin assay revealed that treatment with VOSO4 for 24 and 48 h at concentrations of 50 and 100 µM, respectively, or higher substantially induced astrocytic cytotoxicity. Intracellular ROS increased after 6-h exposure to the lowest concentration tested (20 µM VOSO4 ) and tended to intensify after 24- and 48-h treatments reaching significant values for 20 and 500 µM VOSO4 . In turn, NO production in the examined cells was elevated after exposure to all concentrations at the 6-, 24-, and 48-h incubation periods. Our study demonstrated the ability of VOSO4 to induce H2 O2 generation in cell-free DMEM/F12 medium. The H2 O2 levels were in the micromolar range (up to 5 µM) and were detected mostly during the first few minutes after VOSO4 addition, suggesting that the generated H2 O2 could not induce toxic effects on the cells. Taken together, these results show VOSO4 induced cytotoxicity in primary astrocyte cells, which may have resulted from vanadyl-stimulated intracellular ROS and NO generation in these cells.

Long-term, medium-term and acute stress response of urban populations of Eurasian red squirrels affected by different levels of human disturbance.

Animals in urban areas often encounter novel and potentially stressful conditions. It is important to understand how wildlife cope with anthropogenic disturbance. To investigate this specific adaptation we live-trapped squirrels in two study sites in Warsaw: a forest reserve and an urban park and we estimated stress responses at three levels: long-term and medium-term stress (the level of stress hormones, i.e. cortisol and cortisone concentrations, in hair and feces) and acute reaction to human-induced stress (measured during handling with the aid of the three indices: breath rate, struggle rate, and vocalization). According to GLMM models no difference in the stress hormones level was found between the two populations. The only differences in cortisol concentrations clearly depended on the season, i.e. being higher in autumn and winter comparying to other seasons. There was no influence of sex, or reproductive status on stress hormones. Forest squirrels had significantly higher breath rates, suggesting they were more stressed by handling. There was no difference in the struggle rate between study areas, this index was mostly affected by season (i.e. being highest in winter). First-trapped squirrels vocalized less than during the subsequent trappings. Assumingly, during the first, and more stressful trapping, squirrels used 'freezing' and/or little vocalization, while during next captures they used alarm calls to warn conspecifics. Overall, we showed that the two squirrel populations differed only in terms of their breath rate. This suggests that they did not differ in medium-term and long-term stress in general, but they can differ in acute response to handling. This also suggests that both populations were similarly affected by environmental factors. The lack of clear effects may also be due to population heterogeneity. Thus, in order to assess the effects of anthropogenic stressors a broader range of indicators and diverse analytical methods, including behavioral analyses, should be employed.

Inhibitory and stimulating effect of magnesium on vanadate-induced lipid peroxidation under in vitro conditions.

The behaviour of Mg related to vanadium(V)-induced lipid peroxidation (LPO) under in vitro conditions was examined. The studies performed on the liver supernatants (LS) obtained from control, sodium metavanadate-intoxicated, and sodium metavanadate-magnesium sulphate-administered male Wistar rats revealed and confirmed the pro-oxidative potential of V. Simultaneously, they indicated that the improved Mg status may be one of the mechanisms by which the treatment with this element may contribute to reduction of oxidative stress under the conditions of vanadate exposure. On the other hand, the results confirmed that Mg may also stimulate LPO and demonstrated that the incubation conditions and the experimental treatment of the rats from which the liver supernatants were obtained affect the intensity of the examined free radical process.

Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions.

In the present Special Issue on "Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions", an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties [...].

Overview of Research on Vanadium-Quercetin Complexes with a Historical Outline.

The present review was conducted to gather the available literature on some issues related to vanadium-quercetin (V-QUE) complexes. It was aimed at collecting data from in vitro and in vivo studies on the biological activity, behavior, antioxidant properties, and radical scavenging power of V-QUE complexes. The analysis of relevant findings allowed summarizing the evidence for the antidiabetic and anticarcinogenic potential of V-QUE complexes and suggested that they could serve as pharmacological agents for diabetes and cancer. These data together with other well-documented biological properties of V and QUE (common for both), which are briefly summarized in this review as well, may lay the groundwork for new therapeutic treatments and further research on a novel class of pharmaceutical molecules with better therapeutic performance. Simultaneously, the results compiled in this report point to the need for further studies on complexation of V with flavonoids to gain further insight into their behavior, identify species responsible for their physiological activity, and fully understand their mechanism of action.

Elements and COVID-19: A Comprehensive Overview of Studies on Their Blood/Urinary Levels and Supplementation with an Update on Clinical Trials.

The current report provides a brief overview of the clinical features, hematological/biochemical abnormalities, biomarkers, and AI-related strategies in COVID-19; presents in a nutshell the pharmacological and non-pharmacological therapeutic options; and concisely summarizes the most important aspects related to sociodemographic and behavioral factors as well as comorbidities having an impact on this disease. It also gives a brief outline of the effect of selected elements on immune response and collects data on the levels of micro-/macro-elements and toxic metals in the blood/urine of SARS-CoV-2 infected patients and on supplementation with minerals in COVID-19 subjects. Moreover, this review provides an overview of clinical trials based on the use of minerals alone or in combination with other agents that can provide effective responses toward SARS-CoV-2 infection. The knowledge compiled in this report lays the groundwork for new therapeutic treatments and further research on biomarkers that should be as informative as possible about the patient's condition and can provide more reliable information on COVID-19 course and prognosis. The collected results point to the need for clarification of the importance of mineral supplementation in COVID-19 and the relationships of the levels of some minerals with clinical improvement.

Response of Cytoprotective and Detoxifying Proteins to Vanadate and/or Magnesium in the Rat Liver: The Nrf2-Keap1 System.

Oxidative stress (OS) is a mechanism underlying metal-induced toxicity. As a redox-active element, vanadium (V) can act as a strong prooxidant and generate OS at certain levels. It can also attenuate the antioxidant barrier and intensify lipid peroxidation (LPO). The prooxidant potential of V reflected in enhanced LPO, demonstrated by us previously in the rat liver, prompted us to analyze the response of the nuclear factor erythroid-derived 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2-Keap1) system involved in cellular regulation of OS to administration of sodium metavanadate (SMV, 0.125 mg V/mL) and/or magnesium sulfate (MS, 0.06 mg Mg/mL). The levels of some Nrf2-dependent cytoprotective and detoxifying proteins, i.e., glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), glutamate cysteine ligase catalytic subunit (GCLC), glutathione synthetase (GSS), NAD(P) H dehydrogenase quinone 1 (NQO1), UDP-glucumno-syltransferase 1 (UGT1), and heme oxygenase 1 (HO-1); glutathione (GSH); metallothionein (MT1); and glutamate-cysteine ligase (GCL) mRNA were measured. We also focused on the V-Mg interactive effects and trends toward interactive action as well as relationships between the examined indices. The elevated levels of Nrf2, GCL mRNA, and GCL catalytic subunit (GCLC) confirm OS in response to SMV and point to the capacity to synthesize GSH. The results also suggest a limitation of the second step in GSH synthesis reflected by the unchanged glutathione synthetase (GSS) and GSH levels. The positive correlations between certain cytoprotective/detoxifying proteins (which showed increasing trends during the SMV and/or MS administration, compared to the control) and between them and malondialdehyde (MDA), the hepatic V concentration/total content, and/or V dose (discussed by us previously) point to cooperation between the components of antioxidant defense in the conditions of the hepatic V accumulation and SMV-induced LPO intensification. The V-Mg interactive effect and trend are involved in changes in Nrf2 and UGT1, respectively. The p62 protein has to be determined in the context of potential inhibition of degradation of Keap1, which showed a visible upward trend, in comparison with the control. The impact of Mg on MT1 deserves further exploration.

Stress hormone level and the welfare of captive European bison (Bison bonasus): the effects of visitor pressure and the social structure of herds.

BACKGROUND: Captive European bison (Bison bonasus) play an active role in conservation measures for this species; this includes education, which may conflict with these animals' welfare. The effect of the presence of visitors on the welfare of captive animals can be negative, positive or neutral. However, the response of a given species to visitors is difficult to predict, since even closely related species display varying levels of tolerance to captivity. The aim of the study was to compare immunoreactive fecal cortisol levels (regarded as an indicator of the level of physiological stress) in groups of captive European bison that differed in terms of their social structure and the level of visitor pressure. The second aim was to determine if there was a correlation between intestinal parasitic burden and immunoreactive fecal cortisol levels. RESULTS: Immunoreactive fecal cortisol levels were not influenced by sex or age. However, study site and the interaction between study site and visitor pressure were statistically significant. European bison in one enclosure presented higher levels of immunoreactive fecal cortisol on weekdays than at weekends. In the other two study sites, the levels did not differ between weekdays and weekends. No correlation was found between parasitological infestation and immunoreactive fecal cortisol levels. CONCLUSIONS: Measurement of fecal cortisol metabolites could be a valuable method for further research into the welfare of European bison in captivity. More subtle factors such as individual animal characteristics, feeding systems, and the arrangement of enclosures can be of great importance in terms of the effect of visitors on animals. The results of this study can be used in guidelines for the management of European bison populations.

Antioxidant enzyme activity and lipid peroxidation in the blood of rats co-treated with vanadium (V(+5)) and chromium (Cr (+3)).

Selected biochemical parameters were studied in the blood of outbred, male Wistar rats which daily received to drink deionized water (Group I, control) or solutions of: sodium metavanadate (SMV; 0.100 mg V/mL)-Group II; chromium chloride (CC; 0.004 mg Cr/mL)-Group III; and SMV-CC (0.100 mg V and 0.004 mg Cr/mL)-Group IV for a 12-week period. The diet and fluid intake, body weight gain, and food efficiency ratio (FER) diminished significantly in the rats of Groups II and IV, compared with Groups I and III. The plasma total antioxidant status (TAS) as well as the MDA and the L: -ascorbic acid level in the erythrocytes (RBCs) remained unchanged in all the groups, whereas the plasma L: -ascorbic acid concentration decreased markedly in Group II, compared with Group III. The activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT), cellular glutathione peroxidase (cGSH-Px), and glutathione reductase (GR) in RBCs remained unaltered in all the treated rats. However, the activity of glutathione S-transferase (GST) and the content of reduced glutathione (GSH) in RBCs decreased and increased, respectively, in Groups II, III, and IV, compared with Group I. A vanadium-chromium interaction which affected the GST activity was also found. To summarize, SMV and CC administered separately or in combination in drinking water for 12 weeks did not alter either lipid peroxidation (LPO) or the activities of Cu,Zn-SOD, CAT, cGSH-Px, and GR, which allows a conclusion that both metals in the doses ingested did not reveal their pro-oxidant potential on RBCs.

Lipid peroxidation in the kidney of rats treated with V and/or Mg in drinking water.

Spontaneous and stimulated lipid peroxidation (LPO) after vanadate and magnesium treatment was studied in kidney supernatants obtained from outbred 5-month-old, albino male Wistar rats. The 2-month-old animals daily received: group I (control), deionized water to drink; group II, water solution of sodium metavanadate, NaVO(3) (SMV, 0.125 mg V ml(-1)); group III, water solution of magnesium sulfate, MgSO(4) (MS, 0.06 mg Mg ml(-1)); and group IV, water solution of SMV-MS at the same concentrations as in groups II and III for V and Mg, respectively, over a 12-week period. FeSO(4), NaVO(3) and MgSO(4) were selected as agents that may modify LPO process in in vitro conditions. Spontaneous malondialdehyde (MDA) levels in kidney supernatants increased significantly in the rats in groups II and IV, compared with groups I and III; and they were also significantly higher in all the groups of rats compared with the liver supernatants. The total antioxidant status (TAS) in groups II and IV tended to be higher too. Vanadium concentration in the kidney of the rats in groups II and IV increased, whereas the kidney Mg content in groups II, III and IV decreased, compared with levels in the liver. As the two-way ANOVA indicated, the changes in the basal MDA level, TAS and Mg concentration in the liver of rats at combined V and Mg application only resulted from independent action of V. As far as the in vitro results are concerned, in the supernatants obtained from the rats in groups II and IV, a significant increase in MDA level was demonstrated in the presence of 30 microm of exogenous FeSO(4) as well as 30, 100, 200 and 400 microm NaVO(3) and 100, 200, 400, 600, 800 and 1000 microm MgSO(4), compared with groups I and III. The 600, 800 and 1000 microm of exogenous MgSO(4) also significantly elevated MDA production in the supernatants obtained from the rats in group III, compared with spontaneously formed MDA in the same supernatants. The three-way ANOVA showed that the changes in LPO induced by in vitro treatment of kidney supernatants with exogenous Fe or V or Mg (600, 800 and 1000 microm) were a consequence of independent action of those metals and they also resulted from the interactions between exogenous Fe (Fe(exog)) and endogenous V (V(end)) and between V(end) and exogenous V (V(exog)). In conclusion, V (as NaVO(3)) consumed by the rats with drinking water at a dose of 12.9 mg V kg(-1) b.w. per 24 h for 12 weeks increased the basal LPO and markedly enhanced TAS in the renal tissue. Its pro-oxidant potential was also found in in vitro conditions. The Mg dose (6 mg Mg kg(-1) b.w. per 24 h) ingested by the rats together with V (12.7 mg V kg(-1) b.w. per 24 h) neither reduced nor intensified the spontaneous LPO, compared with V-only intoxicated animals; however, the stimulating effect of Mg on LPO was revealed in in vitro conditions.

Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends.

BACKGROUND: Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine. OBJECTIVE: This review aims at summarizing the current state of knowledge of the pharmacological potential of V and the mechanisms underlying its anti-viral, anti-bacterial, anti-parasitic, anti-fungal, anti-cancer, anti-diabetic, anti-hypercholesterolemic, cardioprotective, and neuroprotective activity as well as the mechanisms of appetite regulation related to the possibility of using this element in the treatment of obesity. The toxicological potential of V and the mechanisms of its toxic action, which have not been sufficiently recognized yet, as well as key information about the essentiality of this metal, its physiological role, and metabolism with certain aspects on the timeline is collected as well. The report also aims to review the use of V in the implantology and industrial sectors emphasizing the human health hazard as well as collect data on the directions of further research on V and its interactions with Mg along with their character. RESULTS AND CONCLUSIONS: Multidirectional studies on V have shown that further analyses are still required for this element to be used as a metallodrug in the fight against certain life-threatening diseases. Studies on interactions of V with Mg, which showed that both elements are able to modulate the response in an interactive manner are needed as well, as the results of such investigations may help not only in recognizing new markers of V toxicity and clarify the underlying interactive mechanism between them, thus improving the medical application of the metals against modern-age diseases, but also they may help in development of principles of effective protection of humans against environmental/occupational V exposure.

Evaluation of the level of selected iron-related proteins/receptors in the liver of rats during separate/combined vanadium and magnesium administration.

BACKGROUND: The current knowledge about the effects of vanadium (V) on iron (Fe)-related proteins and Fe homeostasis (which is regulated at the systemic, organelle, and cellular levels) is still insufficient. OBJECTIVE: This fact and our earlier results prompted us to conduct studies with the aim to explain the mechanism of anemia accompanied by a rise in hepatic and splenic Fe deposition in rats receiving sodium metavanadate (SMV) separately and in combination with magnesium sulfate (MS). RESULTS: We demonstrated for the first time that SMV (0.125 mg V/mL) administered to rats individually and in conjunction with MS (0.06 mg Mg/mL) for 12 weeks did not cause significant differences in the hepatic hepcidin (Hepc) and hemojuvelin (HJV) concentrations, compared to the control. In comparison with the control, there were no significant changes in the concentration of transferrin receptor 1 (TfR1) in the liver of rats treated with SMV and MS alone (in both cases only a downward trend of 14% and 15% was observed). However, a significant reduction in the hepatic TfR1 level was found in rats receiving SMV and MS simultaneously. In turn, the concentration of transferrin receptor 2 (TfR2) showed an increasing trend in the liver of rats treated with SMV and/or MS. CONCLUSIONS: The experimental data suggest that the pathomechanism of the SMV-induced anemia is not associated with the effect of V on the concentration of Hepc in the liver, as confirmed by the unaltered hepatic HJV and TfR1 levels. Therefore, further studies are needed in order to check whether anemia that developed in the rats at the SMV administration (a) results from the inhibitory effect of V on erythropoietin (EPO) production, (b) is related to the effect of V on the induction of matriptase-2 (TMPRSS6) expression, or (c) is associated with the influence of this metal on haem synthesis.

Lipid peroxidation in the liver of rats treated with V and/or Mg in drinking water.

The effect of V(5+) and Mg treatment on spontaneous and stimulated lipid peroxidation (LPO) was studied in liver supernatants obtained from outbred 5-month-old, albino male Wistar rats. The 2-month-old animals daily received deionized water to drink (control, group I); group II - water solution of NaVO(3) (SMV) at a concentration of 0.125 mg V ml(-1); group III - water solution of MgSO(4) (MS) at a concentration of 0.06 mg Mg ml(-1), group IV - water solution of SMV-MS at the same concentrations as in groups II and III for V and Mg, respectively, over a 12-week period. Three metal salts were selected as agents that may modify the LPO process (FeSO(4), NaVO(3) and MgSO(4)). V-intoxicated rats and those treated with V and Mg in combination had higher liver spontaneous malondialdehyde (MDA) formation, compared with the control and Mg-supplemented animals. In the same groups of animals the total antioxidant status (TAS) was also significantly lowered, in comparison with the control. In the supernatants obtained from the above-mentioned groups of rats a significant increase in MDA concentration was found in the presence of exogenous 30 microm FeSO(4) as well as 30, 100, 200 and 400 microm NaVO(3), compared with groups I and III. Significantly elevated MDA production was also observed in the supernatants obtained from the rats exposed to V and Mg in combination in the presence of exogenous 100 and 200 microm MgSO(4) in comparison with the control and group III as well as in the presence of exogenous 400 and 600 microm MgSO(4) compared only with group III. In vitro treatment with 1000 microm MgSO(4 )of control liver supernatants and those obtained from group III significantly enhanced MDA level, compared with spontaneous MDA formation. The two-way ANOVA indicated that the changes in the basal MDA level and in TAS in the rats at combined V and Mg application, were not due to V-Mg interaction, but resulted from independent action of V. In addition, the three-way ANOVA revealed that the changes in LPO induced by in vitro treatment of liver supernatants with exogenous Fe or V or Mg (600, 800 and 1000 microm) were a consequence of independent action of those metals and they also resulted from the interactions between Fe(exog) and V(end) and between V(end) and V(exog). In conclusion, V consumed by the rats with drinking water at a dose of 12 mg V kg(-1) body weight per 24 h for 12 weeks decreased TAS and enhanced spontaneous LPO in the hepatic tissue, which confirms its pro-oxidant potential, was also found in in vitro conditions with regard to LPO. Mg administered to rats in combination with V, at the concentration used, neither reduced nor intensified the basal LPO, compared with V-only treated animals; however, its stimulating effect on LPO was revealed in in vitro conditions, which requires further study.

Vanadium and Oxidative Stress Markers - In Vivo Model: A Review.

This review article is an attempt to summarize the current state of knowledge of the impact of Vanadium (V) on Oxidative Stress (OS) markers in vivo. It shows the results of our studies and studies conducted by other researchers on the influence of different V compounds on the level of selected Reactive Oxygen Species (ROS)/Free Radicals (FRs), markers of Lipid peroxidation (LPO), as well as enzymatic and non-enzymatic antioxidants. It also presents the impact of ROS/peroxides on the activity of antioxidant enzymes modulated by V and illustrates the mechanisms of the inactivation thereof caused by this metal and reactive oxygen metabolites. It also focuses on the mechanisms of interaction of V with some nonenzymatic compounds of the antioxidative system. Furthermore, we review the routes of generation of oxygen-derived FRs and non-radical oxygen derivatives (in which V is involved) as well as the consequences of FR-mediated LPO (induced by this metal) together with the negative/ positive effects of LPO products. A brief description of the localization and function of some antioxidant enzymes and low-molecular-weight antioxidants, which are able to form complexes with V and play a crucial role in the metabolism of this element, is presented as well. The report also shows the OS historical background and OS markers (determined in animals under V treatment) on a timeline, collects data on interactions of V with one of the elements with antioxidant potential, and highlights the necessity and desirability of conducting studies of mutual interactions between V and antioxidant elements.

Evaluation of lipid peroxidation and the level of some elements in rat erythrocytes during separate and combined vanadium and magnesium administration.

The impact of vanadium (V) and magnesium (Mg) as sodium metavanadate (SMV, 0.125 mg V/ml) and magnesium sulfate (MS, 0.06 mg Mg/ml) on lipid peroxidation (LPO) and selected elements in the rat erythrocytes (RBCs) was investigated. Relationships between some indices determined in RBC were also studied. SMV alone (Group II) elevated the malondialdehyde level (MDARBC) (by 95% and 60%), compared with the control (Group I) and MS-supplemented rats (Group III), respectively, reduced the concentration of CuRBC (by 23.5%), in comparison with Group I, but did not change the levels of NaRBC, KRBC, and CaRBC, whereas MS alone (Group III) only reduced the CuRBC concentration (by 22%), compared with Group I. The SMV + MS combination (Group IV) reduced and elevated the CuRBC (by 24%) and CaRBC (by 111%) concentrations, respectively, in comparison with Groups I and III, and these changes were induced by the V-Mg antagonistic and synergistic interaction, respectively. The combined SMV + MS effect also enhanced the MDARBC level, compared with Groups I (by 79%) and III (by 47%) and slightly limited its concentration, compared with Group II, which, in turn, resulted from the distinct trend toward the V-Mg antagonistic interaction. We can conclude that V (as SMV) is able to stimulate LPO in rat RBCs and that V-Mg interactive effects are involved in changes in CuRBC, CaRBC, and MDARBC. Further studies are needed to elucidate the exact mechanisms of the V-Mg antagonistic/synergistic interactions and to provide insight into the biochemical mechanisms of changes in rats suffering from anemia [1], characterized by a disrupted antioxidant barrier in RBCs [2] and an intensified free radical process in these cells.

Evaluation of lipid peroxidation and antioxidant defense mechanisms in the bone of rats in conditions of separate and combined administration of vanadium (V) and magnesium (Mg).

The impact of vanadium (V) and magnesium (Mg) applied as sodium metavanadate (SMV, 0.125 mg V/ml) and magnesium sulfate (MS, 0.06 mg Mg/ml) on oxidative stress markers in bone of male Wistar rats was investigated. Some of them were also measured in the liver, e.g. l-ascorbic acid (hepatic L-AA). Additionally, relationships between selected indices determined in bone were examined. SMV alone (Group II) did not significantly alter the level of TBARS and the activity of SOD, compared with the control (Group I), but it slightly reduced the GR activity (by 13%) and the L-AA level (by 15.5%). It also markedly lowered the activity of CAT and GPx (by 34% and 29%), and to some degree elevated the activity of GST (by 16%) and the hepatic L-AA level (by 119%). MS alone (Group III) decreased the TBARS level (by 49%), slightly lowered the L-AA concentration (by 14%), and reduced the SOD, GPx, and GR activities (by 31%, 40%, and 28%), but did not change the activity of CAT, compared with the control. Additionally, it elevated the GST activity (by 56%) and the hepatic L-AA level (by 40%). In turn, the SMV + MS combination (Group IV) reduced the TBARS level (by 38%) and the SOD, CAT, GPx, and GR activities (by 61%, 58%, 72%, and 40%) but elevated the GST activity (by 66%), compared with the control. The activity of SOD and GPx in the rats in Group IV was also reduced, compared with Group II (by 61% and 61%) and Group III (by 44% and 54%). In turn, the activities of CAT and GR were decreased, compared with Group III (by 55%) and Group II (by 31%), and the L-AA level was lowered, in comparison with Groups II and III (by 53% and 54%). Further, the concentration of V in the bone of rats in Groups II and IV increased, whereas the concentration of Mg decreased, compared with Groups I and III, in which the V and Mg levels dropped and were not altered, respectively, compared with Group I. The total content of Fe in the bone of rats in Groups II and IV increased, compared with Group III, in which the total Fe content did not change, compared with Group I. In turn, the total bone Cu content significantly decreased in the rats in Groups III and IV, compared with Groups I and II, whereas the total Zn content and the Ca concentration did not change markedly. The results provided evidence that the concentration of V used as SMV did not enhance LPO in bone, whereas Mg, at the selected level, markedly reduced LPO in this tissue. On the other hand, both elements administered separately and in combination disrupted the antioxidant defense mechanisms and homeostasis of some metals in bone tissue, which consequently may have contributed to disturbances in the balance in the activities of osteoblastic and osteoclastic cells, and thereby negatively affected bone health.

Effects of vanadium(V) and/or chromium(III) on L-ascorbic acid and glutathione as well as iron, zinc, and copper levels in rat liver and kidney.

This study investigated the selected parameters of the antioxidant system in liver and kidney after in vivo administration of vanadium and/or chromium in rats. Outbred 2-mo-old albino male Wistar rats received drinking water for 12 wk with either sodium metavanadate (SMV; group II); chromium chloride (Cr; group III); or sodium metavanadate and chromium chloride (SMV-Cr; group IV); and group I (control) received deionized water. Chronic treatment with V alone or in combination with Cr produced a significant increase in kidney relative weight. Further, giving rats V alone also led to a significant elevation in liver relative weight. An increase in hepatic Fe concentration and renal Zn content occurred after treatment with V or Cr, respectively. The rats coadministered V and Cr had significantly higher levels of Fe in liver and Zn in kidneys. Simultaneous administration of these two elements resulted in a significant decrease in renal L-ascorbic acid concentration. V given alone significantly decreased GSH content and GSH/GSSG ratio in liver and kidney as well as increased GSSG concentration in liver, whereas Cr alone produced a significant decrease in GSH content in kidney and GSH/GSSG ratio in both organs. In the SMV-Cr-treated group a significant decrease in renal GSH concentration and GSH/GSSG ratio in both organs occurred. A significant increase in liver GSSG content was also found. The observed significant changes in kidney GSH content and in GSH/GSSG ratio in both rat tissues after Cr might result from the pro-oxidant actions of this metal. Thus, oxidative stress, which is a major pathway for V-induced toxicity, might also be associated with Cr(III)-induced adverse effects in rats.

Combined effect of vanadium(V) and chromium(III) on lipid peroxidation in liver and kidney of rats.

Since chromium(III) was demonstrated to have antioxidative action, we have decided to study the effect of this element on V-induced LPO in liver and kidney of rats. Outbred 2-month-old, albino male Wistar rats received daily, for a period of 12 weeks: group I (control), deionized water to drink; group II, sodium metavanadate (SMV) solution at a concentration of 0.100mgV/mL; group III, chromium chloride (CC) solution at a concentration of 0.004mgCr/mL and group IV, SMV-CC solution at a concentration of 0.100mgV and 0.004mgCr/mL. The particular experimental groups took up with drinking water about 8.6mgV/kg b.w./24h (group II), 0.4mgCr/kg b.w./24h (group III), 9mgV and 0.36mgCr/kg b.w./24h (group IV). The V- or Cr-treated groups had higher concentrations of these two elements in liver and kidney compared to the controls. The administration of vanadium alone caused a significant decrease in fluid intake and in body weight gain compared to the controls. In liver supernatants obtained from all tested rats a statistically significant increase in MDA concentration was demonstrated in spontaneous LPO in comparison with the control rats. Moreover, in rats intoxicated with vanadium alone a statistically significant increase in liver MDA level was observed in the presence of 100microM NaVO(3). Instead, in supernatants of liver received from rats treated with chromium alone, a statistically significant increase in MDA concentration in comparison with the controls was found in the presence of 400microM NaVO(3). In kidney supernatants obtained from rats treated with chromium alone, a statistically significant increase in lipid peroxidation was shown in the presence of 30microM FeSO(4) and 400microM NaVO(3). These results show that the tested doses of vanadium(V) and chromium(III) ingested by rats with their drinking water caused significant alterations in internal organs, especially in liver. Under the conditions of our experiment, Cr(III) did not demonstrate antioxidant action, it rather had an oxidant effect.