Protection of pyrroloquinoline quinone against methylmercury-induced neurotoxicity via reducing oxidative stress

Pyrroloquinoline quinone (PQQ) is a novel redox cofactor and also exists in various foods. In vivo as well as in vitro experimental studies have shown that PQQ functions as an essential nutrient or antioxidant. Methylmercury (MeHg), as a highly toxic environmental pollutant, could elicit central nervous system (CNS) damage. Considering the antioxidant properties of PQQ, this study was aimed to evaluate the effect of PQQ on MeHg-induced neurotoxicity in the PC12 cells. The results showed that, after pre-treatment of PC12 cells with PQQ prior to MeHg exposure, the MeHg-induced cytotoxicity was significantly attenuated and then the percentage of apoptotic cells and the arrest of S-phase in cell cycle were correspondingly reduced. Moreover, PQQ significantly decreased the production of ROS, suppressed the lipid peroxidation and increased the antioxidant enzyme activities in PC12 cells exposed to MeHg. These observations highlighted the potential of PQQ in offering protection against MeHg-induced neuronal toxicity.     

Protective effect of Bacopa monniera on methyl mercury-induced oxidative stress in cerebellum of rats

Methyl mercury (MeHg) is a ubiquitous environmental pollutant leading to neurological and developmental deficits in animals and human beings. Bacopa monniera (BM) is a perennial herb and is used as a nerve tonic in Ayurveda, a traditional medicine system in India. The objective of the present study was to investigate whether Bacopa monniera extract (BME) could potentially inhibit MeHg-induced toxicity in the cerebellum of rat brain. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with BME (40 mg/kg, orally) for 21 days. After the treatment period, we observed that MeHg exposure significantly inhibited the activities of superoxide dismutase, catalase, glutathione peroxidase, and increased the glutathione reductase activity in cerebellum. It was also found that the level of thiobarbituric acid-reactive substances was increased with the concomitant decrease in the glutathione level in MeHg-induced rats. These alterations were prevented by the administration of BME. Behavioral interference in the MeHg-exposed animals was evident through a marked deficit in the motor performance in the rotarod task, which was completely recovered to control the levels by BME administration. The total mercury content in the cerebellum of MeHg-induced rats was also increased which was measured by atomic absorption spectrometry. The levels of NO(2) (-) and NO(3) (-) in the serum were found to be significantly increased in the MeHg-induced rats, whereas treatment with BME significantly decreased their levels in serum to near normal when compared to MeHg-induced rats. These findings strongly implicate that BM has potential to protect brain from oxidative damage resulting from MeHg-induced neurotoxicity in rat.     

Preventive Effects of Dextromethorphan on Methylmercury-Induced Glutamate Dyshomeostasis and Oxidative Damage in Rat Cerebral Cortex

Methylmercury (MeHg) is a well-known environmental pollutant leading to neurotoxicant associated with aberrant central nervous system (CNS) functions, but its toxic mechanisms have not yet been fully recognized. In the present study, we tested the hypothesis that MeHg induces neuronal injury via glutamate (Glu) dyshomeostasis and oxidative damage mechanisms and that these effects are attenuated by dextromethorphan (DM), a low-affinity and noncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist. Seventy-two rats were randomly divided into four groups of 18 animals in each group: control group, MeHg-treated group (4 and 12 μmol/kg), and DM-pretreated group. After the 4-week treatment, we observed that the administration of MeHg at a dose of 12 μmol/kg significantly increased in total mercury (Hg) levels, disrupted Glu metabolism, overexcited NMDARs, and led to intracellular calcium overload in the cerebral cortex. We also found that MeHg reduced nonenzymatic and enzymatic antioxidants, enhanced neurocyte apoptosis, induced reactive oxygen species (ROS), and caused lipid, protein, and DNA peroxidative damage in the cerebral cortex. Moreover, glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) appeared to be inhibited by MeHg exposure. These alterations were significantly prevented by the pretreatment with DM at a dose of 13.5 μmol/kg. In conclusion, these findings strongly implicate that DM has potential to protect the brain from Glu dyshomeostasis and oxidative damage resulting from MeHg-induced neurotoxicity in rat.     

Effect of methylmercury on glutamate metabolism in cerebellar astrocytes in culture

The effect of methylmercury (MeHg) on [U-13C]glutamate metabolism was studied in cerebellar astrocytes using 13C nuclear magnetic resonance spectroscopy. The cells were preincubated in medium containing 25 or 50 microM MeHg and 10% fetal calf serum for 4h and then in medium with [U-13C]glutamate (0.5mM) for 2h. Labeled glutamate, glutamine and aspartate were observed both in the cell extracts and media, labeled glutathione in the cell extracts and labeled lactate and alanine in the media. The amount of glutamate removed from the media was decreased in the 50 microM MeHg group, furthermore, the levels of both labeled and unlabeled glutamine were decreased. This might indicate a decreased synthesis and/or increased degradation. An increase was observed for glutathione in the 25 microM group, which might be due to an upregulated synthesis of glutathione in response to the toxic effects of MeHg. The percentage of [U-13C]glutamate used for the synthesis of metabolites via the tricarboxylic acid cycle was increased in the presence of 50 microM MeHg. However, the percentage used for energy production was decreased in both groups, indicating selective mitochondrial vulnerability due to the inhibitory effect of MeHg.     

Effects of proanthocyanidins from grape seed on treatment of recurrent ulcerative colitis in rats

The aim of the present study was to investigate the therapeutic effect and mechanism of proanthocyanidins from grape seed (GSPE) in the treatment of recurrent ulcerative colitis (UC) in rats. To induce recurrent colitis, rats were instilled with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (80?mg/kg) into the colon through the cannula in the first induced phase, and then the rats were instilled a second time with TNBS (30?mg/kg) into the colon on the sixteenth day after the first induction UC. Rats were intragastrically administered GSPE (200?mg/kg) per day for 7?days after twice-induced colitis by TNBS. Sulfasalazine at 500?mg/kg was used as a positive control drug. Rats were killed 7?days after GSPE treatment. The colonic injury and inflammation were assessed by macroscopic and macroscopic damage scores, colon weight/length ratio (mg/cm), and myeloperoxidase activity. Then, superoxide dismutase, glutathione peroxidase, inducible nitric oxide synthase (iNOS) activities, and the levels of malonyldialdehyde, glutathione, and nitric oxide in serum and colonic tissues were measured. Compared with the recurrent UC group, GSPE treatment facilitated recovery of pathologic changes in the colon after induction of recurrent colitis, as demonstrated by reduced colonic weight/length ratio and macroscopic and microscopic damage scores. The myeloperoxidase and iNOS activities with malonyldialdehyde and nitric oxide levels in serum and colon tissues of colitis rats were significantly decreased in the GSPE group compared with those in the recurrent UC group. In addition, GSPE treatment was associated with notably increased superoxide dismutase, glutathione peroxidase activities, and glutathione levels of colon tissues and serum of rats. GSPE exerted a protective effect on recurrent colitis in rats by modifying the inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, and inhibiting colonic iNOS activity to reduce the production of nitric oxide.     

Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies

Neurological disorders are common, costly, and can cause enduring disability. Although mostly unknown, a few environmental toxicants are recognized causes of neurological disorders and subclinical brain dysfunction. One of the best known neurotoxins is methylmercury (MeHg), a ubiquitous environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. In the aquatic environment, MeHg is accumulated in fish, which represent a major source of human exposure. Although several episodes of MeHg poisoning have contributed to the understanding of the clinical symptoms and histological changes elicited by this neurotoxicant in humans, experimental studies have been pivotal in elucidating the molecular mechanisms that mediate MeHg-induced neurotoxicity. The objective of this mini-review is to summarize data from experimental studies on molecular mechanisms of MeHg-induced neurotoxicity. While the full picture has yet to be unmasked, in vitro approaches based on cultured cells, isolated mitochondria and tissue slices, as well as in vivo studies based mainly on the use of rodents, point to impairment in intracellular calcium homeostasis, alteration of glutamate homeostasis and oxidative stress as important events in MeHg-induced neurotoxicity. The potential relationship among these events is discussed, with particular emphasis on the neurotoxic cycle triggered by MeHg-induced excitotoxicity and oxidative stress. The particular sensitivity of the developing brain to MeHg toxicity, the critical role of selenoproteins and the potential protective role of selenocompounds are also discussed. These concepts provide the biochemical bases to the understanding of MeHg neurotoxicity, contributing to the discovery of endogenous and exogenous molecules that counteract such toxicity and provide efficacious means for ablating this vicious cycle.     

Memantine,a Low-Affinity NMDA Receptor Antagonist,Protects against Methylmercury-Induced Cytotoxicity of Rat Primary Cultured Cortical Neurons,Involvement of Ca<Superscript>2+</Superscript> Dyshomeostasis Antagonism,and Indirect Antioxidation Effects

Methylmercury (MeHg) is an extremely dangerous environmental pollutant that induces severe toxic effects in the central nervous system. Neuronal damage plays critical roles mediating MeHg-induced loss of brain function and neurotoxicity. The molecular mechanisms of MeHg neurotoxicity are incompletely understood. The objective of the study is to explore mechanisms that contribute to MeHg-induced neurocyte injuries focusing on neuronal Ca²⁺ dyshomeostasis and alteration of N-methyl-D-aspartate receptors (NMDARs) expression, as well as oxidative stress in primary cultured cortical neurons. In addition, the neuroprotective effects of memantine against MeHg cytotoxicity were also investigated. The cortical neurons were exposed to 0, 0.01, 0.1, 1, or 2 μM methylmercury chloride (MeHgCl) for 0.5–12 h, or pre-treated with 2.5, 5, 10, or 20 μM memantine for 0.5–6 h, respectively; cell viability and LDH release were then quantified. For further experiments, 2.5, 5, and 10 μM of memantine pre-treatment for 3 h followed by 1 μM MeHgCl for 6 h were performed for evaluation of neuronal injuries, specifically addressing apoptosis; intracellular free Ca²⁺ concentrations; ATPase activities; calpain activities; expressions of NMDAR subunits (NR1, NR2A, NR2B); NPSH levels; and ROS formation. Exposure of MeHgCl resulted in toxicity of cortical neurons, which were shown as a loss of cell viability, high levels of LDH release, morphological changes, and cell apoptosis. Moreover, intracellular Ca²⁺ dyshomeostasis, ATPase activities inhibition, calpain activities, and NMDARs expression alteration were observed with 1 μM MeHgCl administration. Last but not least, NPSH depletion and reactive oxygen species (ROS) overproduction showed an obvious oxidative stress in neurons. However, memantine pre-treatment dose-dependently antagonized MeHg-induced neuronal toxic effects, apoptosis, Ca²⁺ dyshomeostasis, NMDARs expression alteration, and oxidative stress. In conclusion, the cytoprotective effects of memantine against MeHg appeared to be mediated not only via its NMDAR binding properties and Ca²⁺ homeostasis maintenance but also by indirect antioxidation effects.     

Platelet oxygen consumption as a peripheral blood marker of brain energetics in a mouse model of severe neurotoxicity

Interactions of chemicals with cerebral cellular systems are often accompanied by similar changes involving components in non-neural tissues. On this basis, indirect strategies have been developed to investigate neural cell function parameters by methods using accessible cells, including platelets and/or peripheral blood lymphocytes. Therefore, here it was investigated whether peripheral blood markers may be useful for assessing the central toxic effects of methylmercury (MeHg). For this purpose, we investigated platelet mitochondrial physiology in a well-established mouse model of MeHg-induced neurotoxicity, and correlated this peripheral activity with behavioural and central biochemical parameters. In order to characterize the cortical toxicity induced by MeHg (20 and 40 mg/L in drinking water, 21 days), the behavioral parameter namely, short-term object recognition, and the central mitochondrial impairment assessed by measuring respiratory complexes I-IV enzyme activities were determined in MeHg-poisoned animals. Neurotoxicity induced by MeHg exposure provoked compromised cortical activity (memory impairment) and reduced NADH dehydrogenase, complex II and II-III activities in the cerebral cortex. These alterations correlated with impaired systemic platelet oxygen consumption of intoxicated mice, which was characterized by reduced electron transfer activity and uncoupled mitochondria. The data brought here demonstrated that impaired systemic platelet oxygen consumption is a sensitive and non-invasive marker of the brain energy deficits induced by MeHg poisoning. Finally, brain and platelets biochemical alterations significantly correlated with cognitive behavior in poisoned mice. Therefore, it could be proposed the use of platelet oxygen consumption as a peripheral blood marker of brain function in a mouse model MeHg-induced neurotoxicity.     

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.     

Post-translational modifications in MeHg-induced neurotoxicity

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.     

Grape seed procyanidin extract attenuates hypoxic pulmonary hypertension by inhibiting oxidative stress and pulmonary arterial smooth muscle cells proliferation

Hypoxia-induced oxidative stress and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Grape seed procyanidin extract (GSPE) possesses antioxidant properties and has beneficial effects on the cardiovascular system. However, the effect of GSPE on HPH remains unclear. In this study, adult Sprague–Dawley rats were exposed to intermittent chronic hypoxia for 4 weeks to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio and median width of pulmonary arteries. GSPE attenuated the elevation of RVSP, RV/LV+S, and reduced the pulmonary vascular structure remodeling. GSPE also increased the levels of SOD and reduced the levels of MDA in hypoxia-induced HPH model. In addition, GSPE suppressed Nox4 mRNA levels, ROS production and PASMCs proliferation. Meanwhile, increased expression of phospho-STAT3, cyclin D1, cyclin D3 and Ki67 in PASMCs caused by hypoxia was down-regulated by GSPE. These results suggested that GSPE might potentially prevent HPH via antioxidant and antiproliferative mechanisms.     

Effect of Bacopa monniera Extract on Methylmercury-Induced Behavioral and Histopathological Changes in Rats

Methylmercury (MeHg) is a well-recognized environmental contaminant with established health risk to human beings by fish and marine mammal consumption. Bacopa monniera (BM) is a perennial herb and is used as a nerve tonic in Ayurveda, a traditional medicine system in India. This study was aimed to evaluate the effect of B. monniera extract (BME) on MeHg-induced toxicity in rat cerebellum. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with BME (40 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After treatment period, MeHg exposure significantly decreases the body weight and also caused the following behavioral changes. Decrease tail flick response, longer immobility time, significant decrease in motor activity, and spatial short-term memory. BME pretreatment reverted the behavioral changes to normal. MeHg exposure decreases the DNA and RNA content in cerebellum and also caused some pathological changes in cerebellum. Pretreatment with BME restored all the changes to near normal. These findings suggest that BME has a potent efficacy to alleviate MeHg-induced toxicity in rat cerebellum.     

Excess Manganese-Induced Apoptosis in Chicken Cerebrums and Embryonic Neurocytes

Methyl mercury (MeHg) is a developmental neurotoxin that causes irreversible cognitive damage in offspring of gestationally exposed mothers. Currently, no preventive drugs are established against MeHg developmental neurotoxicity. The neuroprotective effect of gestational administration of a flavanoid against in utero toxicity of MeHg is not explored much. Hence, the present study validated the effect of a bioactive flavanoid, fisetin, on MeHg developmental neurotoxicity outcomes in rat offspring at postnatal weaning age. Pregnant Wistar rats were simultaneously given MeHg (1.5 mg/kg b.w.) and two doses of fisetin (10 and 50 mg/kg b.w. in two separate groups) orally from gestational day (GD) 5 till parturition. Accordingly, after parturition, on postnatal day (PND) 24, weaning F₁ generation rats were studied for motor and cognitive behavioural changes. Biochemical and histopathological changes were also studied in the cerebral cortex, cerebellum and hippocampus on PND 25. Administration of fisetin during pregnancy prevented behavioural impairment due to transplacental MeHg exposure in weaning rats. Fisetin decreased the levels of oxidative stress markers, increased enzymatic and non-enzymatic antioxidant levels and increased the activity of membrane-bound ATPases and cholinergic function in F₁ generation rats. In light microscopic studies, fisetin treatment protected the specific offspring brain regions from significant morphological aberrations. Between the two doses of fisetin studied, 10 mg/kg b.w. was found to be more satisfactory and effective than 50 mg/kg b.w. The present study shows that intake of fisetin during pregnancy in rats ameliorated in utero MeHg exposure-induced neurotoxicity outcomes in postnatal weaning F₁ generation rats.     

The magnitude of methylmercury-induced cytotoxicity and cell cycle arrest is p53-dependent

BACKGROUND: Methylmercury (MeHg), a ubiquitous environmental contaminant, is a known potent teratogen selectively affecting the developing central nervous system. While a definitive mechanism for MeHg-induced developmental neurotoxicity remains elusive, in utero exposure has been associated with reduced brain weight and reduction in cell number. This suggests early toxicant interference with critical molecular signaling events controlling cell behavior, i.e., proliferation. METHODS: To examine the role of p53, a major regulator of the G(1)/S and G(2)/M cell cycle checkpoints, in MeHg toxicity, we isolated GD 14 primary embryonal fibroblasts from homozygous wild-type p53 (p53+/+) and homozygous null p53 (p53-/-) mice. Cells were treated at passages 4-7 for 24 or 48 hr with 0, 1.0, or 2.5 microM MeHg and analyzed for effects on viability, cell cycle progression (using BrdU-Hoechst flow cytometric analysis), and apoptosis via annexin V-FITC and propidium iodide (PI) staining. RESULTS: The p53+/+ cells are more sensitive than p53-/- cells to MeHg-induced cytotoxicity, cell cycle inhibition, and induction of apoptosis: at 24 hr, 2.5 microM MeHg reduced p53+/+ cell viability to 72.6% +/- 3.2%, while p53-/- viability was 94.6% +/- 0.4%. The p53-/- cells underwent less necrosis and less apoptosis following MeHg treatment. MeHg (2.5 microM) also halted all cycling in the p53+/+ cells, while 42.6% +/- 7.2% of p53-/- cells were able to reach a new G(0)/G(1) in 48 hr. Time- and dose-dependent accumulation of cells in G(2)/M phase (1.0 and 2.5 microM MeHg) was observed independent of the p53 genotype; however, the magnitude of change was p53-dependent. CONCLUSIONS: These studies suggest that MeHg-induced cell cycle arrest occurs via both p53-dependent and -independent pathways in our model system; however, cell death resulting from MeHg exposure is highly dependent on p53.     

Exposure to Zinc Oxide Nanoparticles Induces Neurotoxicity and Proinflammatory Response: Amelioration by Hesperidin

Zinc oxide nanoparticles (ZnONPs) are widely used in food packaging and may enter the body directly if exposed. Hereby, in this study, the oral administration was selected as the route of exposure for rats to nanoparticles and the effect of hesperidin (HSP, 100 mg/kg bwt) was evaluated on ZnONP (600 mg/kg bwt)-induced neurotoxicity in rats. ZnONPs were characterized using transmission electron microscopy. Neurotoxicity was observed as seen by elevation in serum inflammatory markers including tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1β), interleukin-6 (IL-6), C-reactive protein (CRP), and activities of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH) content in rat brains. Pretreatment of rats with HSP in ZnONP-treated group elevated activities of antioxidant enzymes. HSP also caused decrease in TNF-α, IL-1β, IL-6, and CRP levels which was higher in the ZnONP-treated group. The results suggest that HSP augments antioxidant defense with anti-inflammatory response against ZnONP-induced neurotoxicity. The increased antioxidant enzymes enhance the antioxidant potential to reduce oxidative stress.     

Selenium prevents downregulation of antioxidant selenoprotein genes by methylmercury

Selenium (Se) is an essential nutrient required by Se-dependent proteins, termed selenoproteins. The selenoprotein family is small but diverse and includes key proteins in antioxidant, redox signaling, thyroid hormone metabolism, and protein folding pathways. Methylmercury (MeHg) is a toxic environmental contaminant that affects seafood safety. Selenium can reduce MeHg toxicity, but it is unclear how selenoproteins are affected in this interaction. In this study we explored how Se and MeHg interact to affect the mRNA expression of selenoprotein genes in whole zebrafish (Danio rerio) embryos. Embryos were obtained from adult zebrafish fed MeHg with or without elevated Se in a 2×2 factorial design. The embryo mRNA levels of 30 selenoprotein genes were then measured. These genes cover most of the selenoprotein families, including members of the glutathione peroxidase (GPX), thioredoxin reductase, iodothyronine deiodinase, and methionine sulfoxide reductase families, along with selenophosphate synthetase 2 and selenoproteins H, J-P, T, W, sep15, fep15, and fam213aa. GPX enzyme activity and larval locomotor activity were also measured. We found that around one-quarter of the selenoprotein genes were downregulated by elevated MeHg. These downregulated genes were dominated by selenoproteins from antioxidant pathways that are also susceptible to Se-deficiency-induced downregulation. MeHg also decreased GPX activity and induced larval hypoactivity. Elevated Se partially prevented MeHg-induced disruption of selenoprotein gene mRNA levels, GPX activity, and larval locomotor activity. Overall, the MeHg-induced downregulation and subsequent rescue by elevated Se levels of selenogenes regulated by Se status suggest that Se deficiency is a contributing factor to MeHg toxicity.     

Human-induced pluripotent stems cells as a model to dissect the selective neurotoxicity of methylmercury

Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS) with apparent indiscriminate disruption of multiple homeostatic pathways. However, genetic and environmental modifiers contribute significant variability to neurotoxicity associated with human exposures. MeHg displays developmental stage and neural lineage selective neurotoxicity. To identify mechanistic-based neuroprotective strategies to mitigate human MeHg exposure risk, it will be critical to improve our understanding of the basis of MeHg neurotoxicity and of this selective neurotoxicity. Here, we propose that human-based pluripotent stem cell cellular approaches may enable mechanistic insight into genetic pathways that modify sensitivity of specific neural lineages to MeHg-induced neurotoxicity. Such studies are crucial for the development of novel disease modifying strategies impinging on MeHg exposure vulnerability.     

Hepatoprotective and antioxidant effect of tender coconut water on carbon tetrachloride induced liver injury in rats

Hepatoprotective and antioxidant effects of tender coconut water (TCW) were investigated in carbon tetrachloride (CCl4)-intoxicated female rats. Liver damage was evidenced by the increased levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and decreased levels of serum proteins and by histopathological studies in CCl4-intoxicated rats. Increased lipid peroxidation was evidenced by elevated levels of thiobarbituric acid reactive substance (TBARS) viz, malondialdehyde (MDA), hydroperoxides (HP) and conjugated dienes (CD), and also by significant decrease in antioxidant enzymes activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx) and glutathione reductase (GR) and also reduced glutathione (GSH) content in liver. On the other hand, CCl4-intoxicated rats treated with TCW retained almost normal levels of these constituents. Decreased activities of antioxidant enzymes in CCl4-intoxicated rats and their reversal of antioxidant enzyme activities in TCW treated rats, shows the effectiveness of TCW in combating CCl4-induced oxidative stress. Hepatoprotective effect of TCW is also evidenced from the histopathological studies of liver, which did not show any fatty infiltration or necrosis, as observed in CCl4-intoxicated rats.