Effectiveness of (PhSe)2 in protect against the HgCl2 toxicity

This work investigated the preventive effect of diphenyl diselenide [(PhSe)₂] on renal and hepatic toxicity biomarkers and oxidative parameters in adult mice exposed to mercury chloride (HgCl₂). Selenium (Se) and mercury (Hg) determination was also carried out. Mice received a daily oral dose of (PhSe)₂ (5.0 mg/kg/day) or canola oil for five consecutive days. During the following five days, the animals were treated with a daily subcutaneous dose of HgCl₂ (5.0 mg/kg/day) or saline (0.9%). Twenty-four hours after the last HgCl₂ administration, the animals were sacrificed and biological material was obtained. Concerning toxicity biomarkers, Hg exposure inhibited blood δ-aminolevulinic acid dehydratase (δ-ALA-D), serum alanine aminotransferase (ALT) activity and also increased serum creatinine levels. (PhSe)₂ partially prevented blood δ-ALA-D inhibition and totally prevented the serum creatinine increase. Regarding the oxidative parameters, Hg decreased kidney TBARS levels and increased kidney non-protein thiol levels, while (PhSe)₂ pre-treatment partially protected the kidney thiol levels increase. Animals exposed to HgCl₂ presented Hg content accumulation in blood, kidney and liver. The (PhSe)₂ pre-treatment increased Hg accumulation in kidney and decreased in blood. These results show that (PhSe)₂ can be efficient in protecting against these toxic effects presented by this Hg exposure model.     

Effect of Electron Donor to Sulfate Ratio on Mercury Methylation in Floodplain Sediments under Saturated Flow Conditions

A column transport experiment was conducted to examine the release and methylation of Hg using Hg contaminated sediment from the floodplain of the South River near Waynesboro, Virginia. Three input solutions were sequentially introduced into the column. Input 1 was unamended South River water, Input 2 was river water amended with 100 mg L^?1 SO₄ and 3600 mg L^?1 lactate, and Input 3 was river water amended with 500 mg L^?1 SO₄ and 340 mg L^?1 lactate. During the first stage of the experiment (Input 1) the effluent Hg concentration was initially 4 µg L^?1 and peaked at 21 µg L^?1 and after 21 pore volumes stabilized at 13 µg L^?1. During the second stage, at high lactate to SO₄ ratios, elevated concentrations of acetic and propionic acids were detected, indicating that fermentative bacteria were dominant. During the third stage, at high SO₄ to lactate ratios, a decrease in SO₄ and an increase in H₂S concentrations were detected in the column effluent indicating that SO₄ reduction was occurring. Concentrations of methyl Hg (MeHg) in the effluent were variable over the duration of the experiment. During the first phase, concentrations of MeHg remained <3.3 ng L^?1. During the fermentative stage, concentrations of MeHg increased to a maximum value of 32 ng L^?1, and during the sulfate-reducing stage to a maximum value of 266 ng L^?1. When the column was deconstructed both molecular and cultural techniques indicated that sulfate reducing bacteria were most dominant near the influent port. These results indicate that the formation of MeHg in the sediment is not limited by the availability of Hg and that the bacterial community that contributes to mercury methylation can respond quickly to changes in the abundances of electron donors and acceptors.     

Antifungal Activities of Diphenyl Diselenide alone and in Combination with Fluconazole or Amphotericin B against Candida glabrata

Here, we evaluated combinations of diphenyl diselenide [(PhSe)₂] with fluconazole and amphotericin B in a checkerboard assay against clinical Candida glabrata strains. Minimal inhibitory concentration (geometric mean) ranged from 0.25 to >64 (5.16 μg/mL) for (PhSe)₂, 1 to 32 (5.04 μg/mL) for fluconazole and 0.06 to 0.5 (0.18 μg/mL) for amphotericin B. Synergistic (76.66 %) and indifferent (23.34 %) interactions were observed for (PhSe)₂ + amphotericin B combination. (PhSe)₂ + fluconazole combination demonstrated indifferent (50 %) and antagonistic (40 %) interactions, whereas synergistic interactions were observed in 10 % of the isolates. New experimental in vivo protocols are necessary and will promote a better understanding of the antimicrobial activity of (PhSe)₂ against C. glabrata and its use as an adjuvant therapy with antifungal agents.     

Selenoneine, a Novel Selenium-Containing Compound, Mediates Detoxification Mechanisms against Methylmercury Accumulation and Toxicity in Zebrafish Embryo

The selenium (Se)-containing antioxidant selenoneine (2-selenyl-N _α,N _α,N _α-trimethyl-l-histidine) has recently been discovered to be the predominant form of organic Se in tuna blood. Although dietary intake of fish Se has been suggested to reduce methylmercury (MeHg) toxicity, the molecular mechanism of MeHg detoxification by Se has not yet been determined. Here, we report evidence that selenoneine accelerates the excretion and demethylation of MeHg, mediated by a selenoneine-specific transporter, organic cations/carnitine transporter-1 (OCTN1). Selenoneine was incorporated into human embryonic kidney HEK293 cells transiently overexpressing OCTN1 and zebrafish blood cells by OCTN1. The K _m for selenoneine uptake was 13.0 μM in OCTN1-overexpressing HEK293 cells and 9.5 μM in zebrafish blood cells, indicating high affinity of OCTN1 for selenoneine in human and zebrafish cells. When such OCTN1-expressing cells and embryos were exposed to MeHg–cysteine (MeHgCys), MeHg accumulation was decreased and the excretion and demethylation of MeHg were enhanced by selenoneine. In addition, exosomal secretion vesicles were detected in the culture water of embryos that had been microinjected with MeHgCys, suggesting that these may be responsible for MeHg excretion and demethylation. In contrast, OCTN1-deficient embryos accumulated MeHg, and MeHg excretion and demethylation were decreased. Furthermore, Hg accumulation was decreased in OCTN1-overexpressing HEK293 cells, but not in mock vector-transfected cells, indicating that selenoneine and OCTN1 can regulate MeHg detoxification in human cells. Thus, the selenoneine-mediated OCTN1 system regulates secretory lysosomal vesicle formation and MeHg demethylation.     

Diphenyl Diselenide Prevents Cortico-cerebral Mitochondrial Dysfunction and Oxidative Stress Induced by Hypercholesterolemia in LDL Receptor Knockout Mice

Recent studies have indicated a causal link between high dietary cholesterol intake and brain oxidative stress. In particular, we have previously shown a positive correlation between elevated plasma cholesterol levels, cortico-cerebral oxidative stress and mitochondrial dysfunction in low density lipoprotein receptor knockout (LDLr^?/?) mice, a mouse model of familial hypercholesterolemia. Here we show that the organoselenium compound diphenyl diselenide (PhSe)₂ (1 mg/kg; o.g., once a day for 30 days) significantly blunted the cortico-cerebral oxidative stress and mitochondrial dysfunction induced by a hypercholesterolemic diet in LDLr^?/? mice. (PhSe)₂ effectively prevented the inhibition of complex I and II activities, significantly increased the reduced glutathione (GSH) content and reduced lipoperoxidation in the cerebral cortex of hypercholesterolemic LDLr^?/? mice. Overall, (PhSe)₂ may be a promising molecule to protect against hypercholesterolemia-induced effects on the central nervous system, in addition to its already demonstrated antiatherogenic effects.     

DMPS and N-acetylcysteine induced renal toxicity in mice exposed to mercury

Acute effects of mercuric chloride (HgCl₂) were evaluated on mice. Mice received a single dose of HgCl₂ (4.6 mg/kg, subcutaneously) for three consecutive days. Thirty minutes after the last injection with HgCl₂, mice received one single injection of 2,3-dimercapto-1-propanesulfonic acid (DMPS) or N-acetylcysteine (NAC) or diphenyl diselenide (PhSe)₂. DMPS, NAC and (PhSe)₂ were utilized as therapy against mercury exposure. At 24 h after the last HgCl₂ injection, blood, liver and kidney samples were collected. δ-Aminolevulinate dehydratase (δ-ALA-D) and Na⁺, K_-⁺ ATPase activities, thiobarbituric acid-reactive substances (TBARS), non-protein thiols (NPSH) and ascorbic acid concentrations were evaluated. Plasma aspartate (AST) and alanine (ALT) aminotransferase activities, as well as urea and creatinine levels were determined. The group of mice exposed to Hg + (PhSe)₂ presented 100% of lethality. Exposure with HgCl₂ caused a decrease on the body weight gain and treatments did not modify this parameter. δ-ALA-D, AST and ALT activities, TBARS, ascorbic acid levels and NPSH (hepatic and erythrocytic) levels were not changed after HgCl₂ exposure. HgCl₂ caused an increase in renal NPSH content and therapies did not modify these levels. Mice treated with (PhSe)₂, Hg + NAC and Hg + DMPS presented a reduction in plasma NPSH levels. Creatinine and urea levels were increased in mice exposed to Hg + NAC, while Hg + DMPS group presented an increase only in urea level. Na⁺, K_-⁺ ATPase activity was inhibited in mice exposed to Hg + DMPS and Hg + NAC. In conclusion, therapies with (PhSe)₂, DMPS and NAC following mercury exposure must be better studied because the formation of more toxic complexes with mercury, which can mainly damage renal tissue.     

Protective Effect of Diphenyl Diselenide on Ischemia and Reperfusion-Induced Cerebral Injury: Involvement of Oxidative Stress and Pro-Inflammatory Cytokines

Cerebrovascular diseases, including ischemic stroke, are associated with high mortality worldwide. Oxidative stress and inflammation are important pathophysiological mechanisms involved in post-ischemic cerebral injury. The present study was designed to investigate the potential protective effect of diphenyl diselenide (PhSe)₂, an organoselenium compound with antioxidant and anti-inflammatory properties, against ischemia/reperfusion (I/R) insult in rat brain. The experimental model adopted was that of surgically-induced brain ischemia, performed by means of bilateral common carotid artery occlusion in rats. The effect of a single oral dose of (PhSe)₂ (50 mg/kg), administered 30 min before the onset of ischemia, was investigated by assessing cerebral oxidative stress-related biochemical parameters and pro-inflammatory cytokines in plasma of rats. The results demonstrated an increase in the levels of malondialdehyde (MDA), reactive oxygen species (ROS) and nitrate/nitrite as well as the alteration in the non-enzymatic and enzymatic (catalase and superoxide dismutase) antioxidant defense system induced by I/R insult in rat brain. I/R insult increased the levels of IL-1β, IL-6, TNF-α and INF-γ in plasma of rats. The administration of (PhSe)₂ restored cerebral levels of MDA, ROS, nitrate/nitrite and antioxidant defenses of rats exposed to I/R insult. (PhSe)₂ markedly reduced pro-inflammatory cytokines in plasma of I/R rats. I/R insult increased the plasma levels of tissue damage markers, such as creatine kinase and α-1-acid glycoprotein. Pretreatment with (PhSe)₂ was effective in reducing the levels of these proteins. In addition, (PhSe)₂ attenuated cerebral histological alterations induced by I/R. This study showed for the first time the in vivo protective effect of (PhSe)₂ against oxidative stress and pro-inflammatory cytokines-induced by I/R insult in rats.     

Dealing with 1,3-bis(4-nitrophenyl)triazene as intermediary ligand in the synthesis of polymeric (μ-Se)Hg-clusters: One-pot synthetic procedures and X-ray structural characterization of [(PhSe)7Hg4BrPy]n

(PhSe)₂Hg reacts initially with HgBr₂ and further with 1,3-bis(4-nitrophenyl)triazene to give [(PhSe)₇Hg₄BrPy]_n (Py = pyridine) the first polymeric assembling of (μ-Se)Hg clusters obtained with a triazene as coordinating intermediary ligand. Each single molecule of adamantane alike [(PhSe)₇Hg₄BrPy] presents the Hg^II ions with a distorted tetrahedral configuration linked through asymmetric [μ-(Ph)Se]⁻ bridges. [(PhSe)₇Hg₄BrPy]_n represents an example of extended one-dimensional chains of closed anisotropic ME (E = S, Se, Te) systems. In these reactions the features of the intermediary ligands should determine the template which leads to single adamantane moieties or to fused ones.     

Protective effects of diphenyl diselenide in a mouse model of brain toxicity

Interest in organoselenide chemistry and biochemistry has increased in the past three decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of the organic selenium compound diphenyl diselenide (PhSe)₂ (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Our group has previously demonstrated that the oral and repeated administration (21 days) of MeHg (40 mg/L) induced MeHg brain accumulation at toxic concentrations, and a pattern of severe cortical and cerebellar biochemical and behavioral. In order to assess neurotoxicity, the neurochemical parameters, namely, mitochondrial complexes I, II, II–III and IV, glutathione peroxidase (GPx) and glutathione reductase (GR) activities, the content of thiobarbituric acid-reactive substances (TBA-RS), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and brain-derived neurotrophic factor (BDNF), as well as, metal deposition were investigated in mouse cerebral cortex. Cortical neurotoxicity induced by brain MeHg deposition was characterized by the reduction of complexes I, II, and IV activities, reduction of GPx and increased GR activities, increased TBA-RS and 8-OHdG content, and reduced BDNF levels. The daily treatment with (PhSe)₂ was able to counteract the inhibitory effect of MeHg on mitochondrial activities, the increased oxidative stress parameters, TBA-RS and 8-OHdG levels, and the reduction of BDNF content. The observed protective (PhSe)₂ effect could be linked to its antioxidant properties and/or its ability to reduce MeHg deposition in brain, which was here histochemically corroborated. Altogether, these data indicate that (PhSe)₂ could be consider as a neuroprotectant compound to be tested under neurotoxicity.     

Root morphology, root-hair development and rhizosheath formation on perennial grass seedlings is influenced by soil acidity

Cadmium (Cd) exerts a detrimental effect on the metabolism of plants, whereas selenium (Se) may protect them against various stressors through its antioxidative activity. In this in vitro study we investigated the impact of Se (2 µM Na₂SeO₄) on the growth, nutrient (P, S, K, Ca, Mg, B, Mn, Fe and Zn) concentrations and cell integrity of rape (Brassica napus oleifera) and two wheat (Triticum aestivum) genotypes subjected to Cd stress (600 µM CdCl₂). Rape accumulated both Cd and Se more than did wheat. In all plants, Cd markedly reduced the biomass, enhanced lipid peroxidation and diminished plasmalemma fluidity. A drop in the K uptake and the reduced plasmalemma permeability diminished the K efflux from the leaf cells. In contrast, Cd elevated S concomitantly with Zn, indicating an activity of detoxifying SH groups and SOD isoenzymes. When added alone, Se promoted the growth of all plants, it enhanced the accumulation of S, but the impact on other nutrients remained minor. In Cd-stressed plants, Se tended to counterbalance the Cd-induced changes in nutrients, it also reduced the lipid peroxidation and exerted positive effects on the cell membrane stability. The Cd stress and the protective role of Se were most evident in rape. The Finnish wheat genotype was less tolerant to Cd than the Polish one.     

A Michaelis–Menten type equation for describing methylmercury dependence on inorganic mercury in aquatic sediments

Methylation of mercury (Hg) is the crucial process that controls Hg biomagnification along the aquatic food chains. Aquatic sediments are of particular interest because they constitute an essential reservoir where inorganic divalent Hg (Hg^II) is methylated. Methylmercury (MeHg) concentrations in sediments mainly result from the balance between methylation and demethylation reactions, two opposite natural processes primarily mediated by aquatic microorganisms. Thus, Hg availability and the activity of methylating microbial communities control the MeHg abundance in sediments. Consistently, some studies have reported a significant positive correlation between MeHg and Hg^II or total Hg (Hg_T), taken as a proxy for Hg^II, in aquatic sediments using enzyme-catalyzed methylation/demethylation mechanisms. By compiling 1,442 published and unpublished Hg_T–MeHg couples from lacustrine, riverine, estuarine and marine sediments covering various environmental conditions, from deep pristine abyssal to heavily contaminated riverine sediments, we show that a Michaelis–Menten type relationship is an appropriate model to relate the two parameters: MeHg = aHg_T/(K _m  + Hg_T), with a = 0.277 ± 0.011 and K _m  = 188 ± 15 (R ² = 0.70, p < 0.001). From K _m variations, which depend on the various encountered environmental conditions, it appears that MeHg formation and accumulation are favoured in marine sediments compared to freshwater ones, and under oxic/suboxic conditions compared to anoxic ones, with redox potential and organic matter lability being the governing factors.     

Patterns of Bacterial Diversity Along a Long-Term Mercury-Contaminated Gradient in the Paddy Soils

Mercury (Hg) pollution is usually regarded as an environmental stress in reducing microbial diversity and altering bacterial community structure. However, these results were based on relatively short-term studies, which might obscure the real response of microbial species to Hg contamination. Here, we analysed the bacterial abundance and community composition in paddy soils that have been potentially contaminated by Hg for more than 600 years. Expectedly, the soil Hg pollution significantly influenced the bacterial community structure. However, the bacterial abundance was significantly correlated with the soil organic matter content rather than the total Hg (THg) concentration. The bacterial alpha diversity increased at relatively low levels of THg and methylmercury (MeHg) and subsequently approached a plateau above 4.86 mg kg^?1 THg or 18.62 ng g^?1 MeHg, respectively. Contrasting with the general prediction of decreasing diversity along Hg stress, our results seem to be consistent with the intermediate disturbance hypotheses with the peak biological diversity under intermediate disturbance or stress. This result was partly supported by the inconsistent response of bacterial species to Hg stress. For instance, the relative abundance of Nitrospirae decreased, while that of Gemmatimonadetes increased significantly along the increasing soil THg and MeHg concentrations. In addition, the content of SO₄ ^2?, THg, MeHg and soil depth were the four main factors influencing bacterial community structures based on the canonical correspondence analysis (CCA). Overall, our findings provide novel insight into the distribution patterns of bacterial community along the long-term Hg-contaminated gradient in paddy soils.     

Diphenyl diselenide modulates nucleotidases,reducing inflammatory responses in the liver of <Emphasis Type="Italic">Toxoplasma gondii</Emphasis>-infected mice

The aim of this study was to verify the effect of diphenyl diselenide (PhSe)₂ on hepatic nucleotidases and on the concentration of purines in mice infected by Toxoplasma gondii. The animals were divided into four groups: Group A (uninfected), Group B (uninfected and treated with (PhSe)₂), Group C (infected), and Group D (infected and treated with (PhSe)₂). The inoculation (groups C and D) was performed with 50 cysts of T. gondii (ME-49 strain). Mice from groups B and D were treated with 5 μmol kg^?1 of (PhSe)₂. Liver tissue from infected mice showed less severe inflammation, elevated ATP/ADO ratio, elevated NTPDase, 5′nucleotidase, and ADA activities compared to the uninfected group (Group A; P < 0.05). However, infected and treated mice showed decreased ATP levels and elevated ADO levels, as well as higher NTPDase and 5′nucleotidase activities and decreased ADA activity in the hepatic tissue compared to the infected group (P < 0.05). Moreover, the (PhSe)₂ treatment of infected mice reduced the hepatic inflammation and showed an immunomodulatory effect on ectonucleotidases of hepatic lymphocytes, which it returned to basal levels. Therefore, chronic infection by T. gondii induces hepatic inflammation in mice, and it is possible that purine levels and nucleotidase activities in hepatic tissue are related to the pathogenesis of the infection in this tissue. The treatment with (PhSe)₂ was able to reverse the hepatic inflammation in mice chronically infected, possibly due to the modulation of purinergic enzymes that produce an anti-inflammatory profile through the purinergic system in the liver tissue.     

Dietary Exposure of the Red-Crowned Crane (Grus japonensis) to Total and Methyl Mercury in Zhalong Wetland,Northeastern China

To determine the dietary exposure of the migratory red-crowned crane to mercury (Hg), this study analyzed the concentrations of total mercury (T-Hg) and methyl mercury (MeHg) in its prey, i.e., reeds and three aquatic animal families (Perccottus glenni Dybowski, Cybister japonicus Sharp, and Viviparidae) in northeastern China. Results indicated that the Hg concentration in Zhalong Wetland was elevated through the food chain, and the prey of the red-crowned crane contained measurable levels of T-Hg and MeHg. In prey tissues, MeHg was the main form of the Hg element and accounted for 61 % of total Hg concentration in Viviparidae, 58 % in C. japonicus Sharp, and 85 % in P. glenni Dybowski. The highest T-Hg and MeHg concentrations ranged from 1.66 to 3.89 ppm and from 1.12 to 2.67 ppm, respectively, and they were detected in the feathers of the red-crowned cranes. The lowest T-Hg concentration was determined in the excretions of wild red-crowned cranes at 0.21 ppm; furthermore, the content of MeHg was below the detection limit. In Zhalong Wetland, the level of dietary exposure of the population of red-crowned cranes to Hg is below the threshold of Hg toxicity. Moreover, eggshells are suitable indicators of Hg risk levels to the red-crowned crane.     

New examples of the exploitation of intermediary ligands in the synthesis of polymeric (μ-Se)Hg-clusters

(PhSe)₂Hg reacts initially with HgX₂ (X = Cl, I) and further with triphenylphosphine/DMF to give [(PhSe)₇Hg₄ClPy]_n (1) and [(PhSe)₇Hg₄I(DMF)]_n (2), polymeric assemblies of (μ-Se)Hg clusters obtained through coordinating intermediary ligands. Each single adamantoid molecule of 1 and 2 presents the Hg^II ions with a distorted tetrahedral configuration linked through asymmetric [μ-(Ph)Se]⁻ bridges. [(PhSe)₇Hg₄ClPy]_n and [(PhSe)₇Hg₄I(DMF)]_n are further examples of extended one-dimensional chains of closed anisotropic ME (E = S, Se, Te) systems. In these reactions the features of the intermediary ligands should determine the template which leads to single adamantane moieties or to fused ones.     

Selenium addition alters mercury uptake,bioavailability in the rhizosphere and root anatomy of rice (Oryza sativa)

Background and Aims

Mercury (Hg) is an extremely toxic pollutant, especially in the form of methylmercury (MeHg), whereas selenium (Se) is an essential trace element in the human diet. This study aimed to ascertain whether addition of Se can produce rice with enriched Se and lowered Hg content when growing in Hg-contaminated paddy fields and, if so, to determine the possible mechanisms behind these effects.

Methods

Two cultivars of rice (Oryza sativa, japonica and indica) were grown in either hydroponic solutions or soil rhizobags with different Se and Hg treatments. Concentrations of total Hg, MeHg and Se were determined in the roots, shoots and brown rice, together with Hg uptake kinetics and Hg bioavailability in the soil. Root anatonmy was also studied.

Key Results

The high Se treatment (5 μg g^–1) significantly increased brown rice yield by 48 % and total Se content by 2·8-fold, and decreased total Hg and MeHg by 47 and 55 %, respectively, compared with the control treatments. The high Se treatment also markedly reduced ‘water-soluble’ Hg and MeHg concentrations in the rhizosphere soil, decreased the uptake capacity of Hg by roots and enhanced the development of apoplastic barriers in the root endodermis.

Conclusions

Addition of Se to Hg-contaminated soil can help produce brown rice that is simultaneously enriched in Se and contains less total Hg and MeHg. The lowered accumulation of total Hg and MeHg appears to be the result of reduced bioavailability of Hg and production of MeHg in the rhizosphere, suppression of uptake of Hg into the root cells and an enhancement of the development of apoplastic barriers in the endodermis of the roots.     

Protective Role of Selenium in Immune-Relevant Cytokine and Immunoglobulin Production by Piglet Splenic Lymphocytes Exposed to Deoxynivalenol

Deoxynivalenol (DON) is a mycotoxin that causes immunosuppression, especially in swine. Selenium (Se) is essential for proper functioning of the immune system in animals. However, little is known about the effects of DON and Se on cytokine or immunoglobulin production in piglets. Here, we addressed this gap by examining piglet splenic lymphocyte responses in vitro. Cells were stimulated with concanavalin A, a T cell stimulatory lectin, in the absence or presence of DON (0.1, 0.2, 0.4, and 0.8 μg/mL), Se (Na₂SeO₃, 2 μM), or combinations of Se 2 μM and DON 0.1–0.8 μg/mL for 12, 24, or 48 h. At each time point, supernatants and cells were collected and the expression of cytokine and immunoglobulin protein and mRNA was examined. Compared with control and Se-alone treatments, DON exposure significantly and dose dependently decreased the expression levels of IL-2, IL-4, IL-6, IL-10, IFN-γ, IgG, and IgM mRNA and protein. By contrast, co-treatment with DON + Se significantly increased the mRNA and protein levels of all factors examined, except IL-4 and IL-6, compared with DON treatment alone. The results of this investigation demonstrate that Se has the potential to counteract DON-induced immunosuppression in piglets and is a promising treatment for DON-mediated toxicity.     

New Therapeutic Approach: Diphenyl Diselenide Reduces Mitochondrial Dysfunction in Acetaminophen-Induced Acute Liver Failure

The acute liver failure (ALF) induced by acetaminophen (APAP) is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe)₂], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe)₂ to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe)₂ to the N-acetylcysteine (NAC) during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg), (PhSe)₂ (15.6 mg/kg), NAC (1200 mg/kg), APAP+(PhSe)₂ or APAP+NAC, where the (PhSe)₂ or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation) and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe)₂. The effectiveness of (PhSe)₂ was similar at a lower dose than NAC. In summary, (PhSe)₂ provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.     

Effects of Selenium and Topiramate on Cytosolic Ca2+ Influx and Oxidative Stress in Neuronal PC12 Cells

It has been widely suggested that selenium (Se) deficiency play an important role in the pathophysiology of epilepsy. It has been reported that Se provides protection against the neuronal damage in patients and animals with epilepsy by restoring the antioxidant defense mechanism. The neuroprotective effects of topiramate (TPM) have been reported in several studies but the putative mechanism of action remains elusive. We investigated effects of Se and TPM in neuronal PC12 cell by evaluating Ca²⁺ mobilization, lipid peroxidation and antioxidant levels. PC12 cells were divided into eight groups namely control, TPM, Se, H₂O₂, TPM + H₂O₂, Se + H₂O₂, Se + TPM and Se + TPM + H₂O₂. The toxic doses and times of H₂O₂, TPM and Se were determined by cell viability assay which is used to evaluate cell viability. Cells were incubated with 0.01 mM TPM for 5 h and 500 nM Se for 10 h. Then, the cells were exposed to 0.1 mM H₂O₂ for 10 h before analysis. The cells in all groups except control, TPM and Se were exposed to H₂O₂ for 15 min before analysis. Cytosolic Ca²⁺ release and lipid peroxidation levels were higher in H₂O₂ group than in control, Se and TPM combination groups although their levels were decreased by incubation of Se and TPM combination. However, there is no difference on Ca²⁺ release in TPM group. Glutathione peroxidase activity, reduced glutathione and vitamin C levels in the cells were lower in H₂O₂ group than in control, Se and TPM groups although their values were higher in the cells incubated with Se and TPM groups than in H₂O₂ groups. In conclusion, these results indicate that Se induced protective effects on oxidative stress in PC12 cells by modulating cytosolic Ca²⁺ influx and antioxidant levels. TPM modulated also lipid peroxidation and glutathione and vitamin C concentrations in the cell system.     

Evaluation of a Questionnaire-Based Method for the Estimation of Methylmercury Exposure of Recreational Anglers in the James Bay Territory (Québec,Canada)

The impoundment of reservoirs temporarily increases the methylation of mercury bound to flooded soils and vegetation and the transfer of methylmercury (MeHg) to fish. MeHg levels in various fish species of hydroelectric reservoirs located in the James Bay territory increased by factors of 3 to 7, then gradually declined toward initial concentrations 10 to 20 years after flooding, depending on reservoir characteristics. The potential risk of increased MeHg exposure for recreational anglers who consume fish from these reservoirs had not been assessed previously. A less invasive method than systematic measurement of Hg levels in hair was developed to determine MeHg exposure of recreational anglers. A fish consumption questionnaire-based approach was combined with a toxicokinetic model to estimate the corresponding hair MeHg concentrations. The results were compared with actual analytical determinations of hair Hg levels for the 94 recreational anglers recruited for the study. The values predicted by the model based on self-reporting consumption overestimated actual hair Hg levels by an average factor greater than 6. The mean hair level predicted for the most recent period (September-October) was 23.3?µg.g^?1 compared to 3.6 µg.g^?1 for the measured value. Although the questionnaire protocol may certainly be improved to increase the precision of estimations, direct hair Hg measurement remains the more effective means to assess Hg exposure.