Drug-induced osteoporosis and mechanisms of bone tissue regeneration through trace elements.

Osteoporosis is associated with an imbalance in bone formation, with certain drugs used in disease treatment being implicated in its development. Supplementation with trace elements may contribute to bone regeneration, offering an alternative approach by enhancing bone mineral density (BMD) and thereby thwarting the onset of osteoporosis. This review aims to assess the mechanisms through which trace elements such as copper (Cu), iron (Fe), selenium (Se), manganese (Mn), and zinc (Zn) are linked to increased bone mass, thus mitigating the effects of pharmaceuticals. Our findings underscore that the use of drugs such as aromatase inhibitors (AIs), proton pump inhibitors (PPIs), antiretrovirals, glucocorticoids, opioids, or anticonvulsants can result in decreased BMD, a primary contributor to osteoporosis. Research indicates that essential elements like Cu, Fe, Se, Mn, and Zn, through various mechanisms, can bolster BMD and forestall the onset of the disease, owing to their protective effects. Consequently, our study recommends a minimum daily intake of these essential minerals for patients undergoing treatment with the aforementioned drugs, as the diverse mechanisms governing the effects of trace elements Cu, Fe, Mn, Se, and Zn facilitate bone remodeling.

Investigation of the cytotoxicity, genotoxicity and antioxidant prospects of JM-20 on human blood cells: A multi-target compound with potential therapeutic applications.

JM-20 is a 1,5-benzodiazepine compound fused to a dihydropyridine fraction with different pharmacological properties. However, its potential toxic effects on blood cells have not yet been reported. Thus, the present study aimed to investigate, for the first time, the possible cytotoxicity of JM-20 through cell viability, cell cycle, morphology changes, reactive species (RS) to DCFH-DA, and lipid peroxidation in human leukocytes, its hemolytic effect on human erythrocytes, and its potential DNA genotoxicity using plasmid DNA in vitro. Furthermore, the compound's ability to reduce the DPPH radical was also measured. Human blood was obtained from healthy volunteers (30 ± 10 years old), and the leukocytes or erythrocytes were immediately isolated and treated with different concentrations of JM-20. A cytoprotective effect was exhibited by 10 µM JM-20 against 1 mM tert-butyl hydroperoxide (t-but-OOH) in the leukocytes. However, the highest tested concentrations of the compound (20 and 50 µM) changed the morphology and caused a significant decrease in the cell viability of leukocytes (p < 0.05, in comparison with Control). All tested concentrations of JM-20 also resulted in a significant increase in intracellular RS as measured by DCFH-DA in these cells (p < 0.05, in comparison with Control). On the other hand, the results point out a potent antioxidant effect of JM-20, which was similar to the classical antioxidant α-tocopherol. The IC50 value of JM-20 against the lipid peroxidation induced by (FeII) was 1.051 µM ± 0.21, while the IC50 value of α-tocopherol in this parameter was 1.065 µM ± 0.34. Additionally, 50 and 100 µM JM-20 reduced the DPPH radical in a statistically similar way to the 100 µM α-tocopherol (p < 0.05, in comparison with the control). No significant hemolysis in erythrocytes, no cell cycle changes in leukocytes, and no genotoxic effects in plasmid DNA were induced by JM-20 at any tested concentration. The in silico pharmacokinetic and toxicological properties of JM-20, derivatives, and nifedipine were also studied. Here, our findings demonstrate that JM-20 and its putative metabolites exhibit similar characteristics to nifedipine, and the in vitro and in silico data support the low toxicity of JM-20 to mammals.

Evaluation of the Neuroprotective Effect of Organic Selenium Compounds: An in Vitro Model of Alzheimer's Disease.

Selenium (Se) is an essential trace element for human health and plays an important role in the development and maintenance of central nervous system functions. Se deficiency has been associated with cognitive decline and increased oxidative stress. The increase in oxidative stress is one of the hypotheses for the emergence and worsening of neurodegenerative diseases, such as Alzheimer's disease (AD). To investigate the neuroprotective effects of organic Se compounds in human neuroblastoma cells (SH-SY5Y) differentiated into cholinergic neurons-like. The SH-SY5Y cells were differentiated into cholinergic neuron-like with retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). AD was mimicked exposing the cells to okadaic acid (OA) and beta-amyloid protein (Aß). The neuroprotective effect of organic Se compounds, selenomethionine (SeMet) and Ebselen, was evaluated through cell viability tests, acetylcholinesterase and antioxidant enzyme activities, and detection of reactive oxygen species (ROS). None of the SeMet concentrations tested protected against the toxic effect of OA + Aß. On the other hand, previous exposure to 0.1 and 1 µM Ebselen protected cells from the toxic effect of OA + Aß. Cell differentiation induced by RA and BDNF exposure was effective, showing characteristics of neuronal cells, and pointing to a promising model of AD. Ebselen showed a protective effect, but more studies are needed to identify the mechanism of action.

Toxicological Effects of Thimerosal and Aluminum in the Liver, Kidney, and Brain of Zebrafish (Danio rerio).

Vaccination programs in the first years of a child's life are effective and extremely important strategies for the successful eradication of diseases. However, as no intervention is without risks, the metal-based components of some vaccines, such as thimerosal (TMS), a preservative composed of ethylmercury, and aluminum (Al), have begun to generate distrust on the part of the population. Therefore, this study evaluated the effects of exposure to thimerosal and aluminum hydroxide (alone or in mixture) on Danio rerio (zebrafish) specimens. The fish were exposed to thimerosal and/or aluminum hydroxide intraperitoneally. The liver, kidney, and brain were removed for a biochemical biomarker analysis, histopathological analysis, and metal quantification. As a result, we observed changes in the activity of the analyzed enzymes (SOD, GST, GPx) in the kidney and brain of the zebrafish, a reduction in GSH levels in all analyzed tissues, and a reduction in MT levels in the kidney and liver as well as in the brain. Changes in AChE enzyme activity were observed. The biochemical results corroborate the changes observed in the lesion index and histomorphology sections. We emphasize the importance of joint research on these compounds to increase the population's safety against their possible toxic effects.

Analysis of the antimelanogenic activity of zinc and selenium in vitro.

Melasma is an acquired chronic condition characterized by hyperchromic patches in photo-exposed areas. The search for new compounds for the treatment of melasma without side effects is constant. In this context, the aim of this study was to investigate the in vitro cytotoxic and antimelanogenic effects of the trace elements Zinc (Zn) and Selenium (Se). In this study, we evaluated the effects of 30 µM hydroquinone, this concentration did not alter mitochondrial function (MTT assay), but increased the percentage of necrotic cells and levels of reactive species. Furthermore, it showed no influence on tyrosinase activity and melanin content. Unlike hydroquinone, exposure for 48 h to 100 µM Zn and 1 and 5 µM Se had no significant influence on the analysis of reactive species, as well as on the percentage of necrotic cells. Still, specifically in relation to 100 µM Zn, it decreased the melanin content. Given the above, the trace elements Zn and Se did not show toxicity at the concentrations tested and Zn showed a promising effect, however, the mechanism needs to be better explored in order to contribute to new and updated research in the fight against melasma with a perspective of therapeutic use.

Antiproliferative Effect of Inorganic and Organic Selenium Compounds in Breast Cell Lines.

Triple-negative breast cancer (TNBC) is an aggressive, fast-growing tumor that is more likely to spread to distant organs. Among women diagnosed with breast cancer, the prevalence of TNBC is 20%, and treatment is currently limited to chemotherapy. Selenium (Se), an essential micronutrient, has been explored as an antiproliferative agent. Therefore, this study aimed to evaluate the effects of exposure to organic (selenomethionine, ebselen, and diphenyl diselenide) and inorganic (sodium selenate and sodium selenite) Se molecules in different breast cell lines. The compounds were tested at 1, 10, 50, and 100 µM for 48 h in the non-tumor breast cell line (MCF-10A) and TNBC derivatives cell lines (BT-549 and MDA-MB-231). The effects of Se on cell viability, apoptotic and necrotic processes, colony formation, and cell migration were analyzed. Exposure to selenomethionine and selenate did not alter the evaluated parameters. However, selenomethionine had the highest selectivity index (SI). The exposure to the highest doses of selenite, ebselen, and diphenyl diselenide resulted in antiproliferative and antimetastatic effects. Selenite had a high SI to the BT cell line; however, the SI of ebselen and diphenyl diselenide was low in both tumoral cell lines. In conclusion, the Se compounds had different effects on the breast cell lines, and additional tests are needed to reveal the antiproliferative effects of Se compounds.

Assessment of Neurotoxic Effects of Oxycodone and Naloxone in SH-SY5Y Cell Line.

Opioid drugs have analgesic properties used to treat chronic and post-surgical pain due to descending pain modulation. The use of opioids is often associated with adverse effects or clinical issues. This study aimed to evaluate the toxicity of opioids by exposing the neuroblastoma cell line (SH-SY5Y) to 0, 1, 10, and 100 µM oxycodone and naloxone for 24 h. Analyses were carried out to evaluate cell cytotoxicity, identification of cell death, DNA damage, superoxide dismutase (SOD), glutathione S-transferase (GST), and acetylcholinesterase (AChE) activities, in addition to molecular docking. Oxycodone and naloxone exposure did not alter the SH-SY5Y cell viability. The exposure to 100 µM oxycodone and naloxone significantly increased the cells' DNA damage score compared to the control group. Naloxone exposure significantly inhibited AChE, GST, and SOD activities, while oxycodone did not alter these enzymes' activities. Molecular docking showed that naloxone and oxycodone interact with different amino acids in the studied enzymes, which may explain the differences in enzymatic inhibition. Naloxone altered the antioxidant defenses of SH-SY5Y cells, which may have caused DNA damage 24 h after the exposure. On the other hand, more studies are necessary to explain how oxycodone causes DNA damage.

Increased Risk of Fractures and Use of Proton Pump Inhibitors in Menopausal Women: A Systematic Review and Meta-Analysis.

Proton pump inhibitors (PPIs) can directly interfere with osteoclastic function, induce hypergastrinemia, and inhibit calcium absorption, leading to reduced bone mineral density (BMD), a measure of bone metabolism that may be associated with the risk of fractures. The current study involves a systematic review and meta-analysis aimed at assessing the relationship between prolonged use of PPI drugs and fractures in menopausal women. A systematic search and meta-analysis were performed on PubMed, Scopus, and Science Direct databases according to PRISMA guidelines. Two independent reviewers analyzed the articles. The five articles found in the databases, which met the eligibility criteria, covered participants who were menopausal women aged between 56 and 78.5 years, using or not using a PPI for a minimum of 12 months. All studies showed an increase in the rate of fractures related to using PPIs, as an outcome. Prolonged use of PPIs in menopausal women can affect bone metabolism and cause fractures. However, other factors, such as the use of other classes of drugs, obesity, low weight, poor diet, replacement hormones, and comorbidities, should also be considered for assessing the risk of fractures.

Effects of Selenium Supplementation in Patients with Mild Cognitive Impairment or Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Elevated levels of oxidative stress could cause and aggravate Alzheimer's disease (AD). Selenium (Se) is a trace element with antioxidant and anti-inflammatory activity with neuroprotective effects. To evaluate the effects of Se supplementation in patients with AD or mild cognitive impairment (MCI) through a systematic review and meta-analysis, data were searched and collected from four electronic databases, including clinical trial studies published until December 2020, following the PRISMA guidelines. Statistical analysis was performed by RevMan, and the risk of bias was assessed using the Rob 2 tool. A total of 1350 scientific papers were collected, and following evaluation 11 papers were included in the systematic review and 6 of these were used in the meta-analysis. Studies that evaluated only Se supplementation observed an improvement in Se levels, glutathione peroxidase (GPX) activity, and in some cognitive tests in MCI patients; similarly, improvement in Se levels and mini-mental score was also observed in AD patients. Regarding supplementation of Se plus other nutrients, improvement in cognitive tests was observed in both AD and MCI patients. Therefore, Se supplementation is a good alternative for patients with AD and MCI for improving Se levels and GPX activity. More detailed studies are required to further evaluate the effects of Se on the cognitive deficit and oxidative stress associated with AD and MCI.

Modification by genetic polymorphism of lead-induced IQ alteration: a systematic review.

As well as a lead-related environmental factor, genetic factors could also corroborate important changes in intelligence quotient (IQ) through single-nucleotide polymorphisms. Thus, a systematic review was carried out to evaluate the possible influence of polymorphism on blood Pb levels and IQ points in pediatric patients (0-19 years old). Following the PRISMA guideline, the studies were systematically collected on PubMed, Scopus, and Embase databases. Six genes (transferrin (TF); glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A); glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B); dopamine receptor D2/ankyrin repeat and kinase domain containing 1 ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1); aminolevulinate dehydratase (ALAD); vitamin D receptor (VDR)) were found in six selected articles. In these genes, 11 single-nucleotide polymorphisms were searched and six different types of variations (missense variant, intron variant, synonymous variant, stop, stop gained) were observed. Due to the few studies in the literature, there is no conclusive data to point out that there is a direct relationship between polymorphisms, Pb levels, and reduction of IQ points.

Mercury toxicity in pregnant and lactating rats: zinc and N-acetylcysteine as alternative of prevention.

This study evaluated the toxic effects of inorganic mercury (Hg) in pregnant and lactating rats, as well as the possible protective effect of zinc (Zn) and N-acetylcysteine (NAC). Pregnant and lactating rats were pre-treated with ZnCl2 (27 mg/kg) and/or NAC (5 mg/kg) and after 24 h, they were exposed to HgCl2 (10 mg/kg). Animals were sacrificed 24 h after Hg exposure, and biochemical tests and metal determination were performed. Regarding pregnant rats, Hg exposure caused kidney, blood, and placenta δ-aminolevulinic acid dehydratase (δ-ALA-D) activity inhibition, and the pre-treatments showed a tendency of protection. Moreover, all the animals exposed to Hg presented high Hg levels in the kidney, liver, and placenta when compared with control group. Pregnant rats pre-exposed to Zn (Zn-Hg and Zn/NAC-Hg groups) presented an increase in hepatic metallothionein levels. Therefore, lactating rats exposed to Hg presented renal and blood δ-ALA-D inhibition; the pre-treatments showed a tendency to prevent the renal δ-ALA-D inhibition and prevented the blood δ-ALA-D inhibition caused by Hg. Lactating rats exposed to Hg presented high Hg levels in the kidney and liver. These results showed that 10 mg/kg of HgCl2 causes biochemistry alterations in pregnant and lactating rats, and Zn and NAC present promising results against these damages.

Simultaneous exposure to vinylcyclohexene and methylmercury in Drosophila melanogaster: biochemical and molecular analyses.

BACKGROUND: Exposure to vinylcyclohexene (VCH) and methylmercury (MeHg+) can induce oxidative stress and gene modulation. Several studies have been evaluating the effects of VCH and MeHg+, but little is known about interactive effects between them. This work aimed to assess the exposure and co-exposure effects of MeHg+ and VCH on oxidative stress and gene modulation in Drosophila melanogaster. METHODS: Reactive species production, glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities were evaluated after exposure and co-exposure to VCH (1 mM) and MeHg+ (0.2 mM) for one or three days in the head and body (thorax and abdomen) of flies. The expression of genes related to redox state and inflammatory response was evaluated after exposure and co-exposure to VCH and MeHg+ for three days. RESULTS: Survival decreased only in flies co-exposed to VCH and MeHg+ for three days. All treatments increased total reactive species production after one day of exposure. However, no significant changes were observed in the head after three days of exposure. One day of exposure to VCH caused an increase in the head GST activity, whereas MeHg+ induced an increase after three days of exposure. Regarding the body, all treatments increased GST activity after one day of exposure, but only the flies exposed to MeHg+ presented an increase in GST activity after three days of exposure. Treatments did not alter AChE activity in the head. As for gene expression, there was a significant increase in the Relish transcription factor gene in the flies' body, but Nrf2, Keap1, Jafrac1, TrxR1, and NF-κß were not altered. CONCLUSION: The results suggest that exposure to VCH and MeHg+ induce oxidative stress and activation of an inflammatory response in fruit flies.

Delta-Aminolevulinate dehydratase and glutathione peroxidase activity in Alzheimer's disease: a case-control study.

Alzheimer's disease (AD) is a neurodegenerative pathology that affects elderly people all over the world. Several studies have demonstrated that oxidative stress is an aggravating factor for AD development and progression. Therefore, this study aimed to evaluate the activity of two oxidative stress markers, glutathione peroxidase (GPx) and δ-aminolevulinate dehydratase (δ-ALA-D), as well as correlate them with blood metal levels and AD progression. For this purpose, 88 elderly individuals were divided in two groups: AD group (34 patients diagnosed with AD) and control group (34 subjects paired by age with the AD group). The Mini-Mental State Examination and the Clinical Dementia Rating (CDR) were used as tools to classify the AD progression. GPx and δ-ALA-D activities were measured in all subjects through blood tests. Both enzymes' activities were decreased in AD patients when compared to the age-matched control group, regardless of the CDR. Moreover, GPx activity was positively correlated with selenium levels in the blood; and the δ-ALA-D activity was negatively correlated with blood copper levels. Taken together, our results indicated that, for the first time, blood δ-ALA-D activity was significantly inhibited in AD patients. While literature reports conflicting data regarding GPx activity in AD patients, the δ-ALA-D activity seems to be a more consistent tool to be applied as an earlier AD marker.

Productivity of CNPq Researchers from Different Fields in Biomedical Sciences: The Need for Objective Bibliometric Parameters-A Report from Brazil.

In Brazil, the CNPq (National Council for Scientific and Technological Development) provides grants, funds and fellowships to productive scientists to support their investigations. They are ranked and categorized into four hierarchical levels ranging from PQ 1A (the highest) to PQ 1D (the lowest). Few studies, however, report and analyse scientific productivity in different sub-fields of Biomedical Sciences (BS), e.g., Biochemistry, Pharmacology, Biophysics and Physiology. In fact, systematic comparisons of productivity among the PQ 1 categories within the above sub-fields are lacking in the literature. Here, the scientific productivity of 323 investigators receiving PQ 1 fellowships (A to D levels) in these sub-fields of BS was investigated. The Scopus database was used to compile the total number of articles, citations, h-index values and authorship positions (first-, co- or last-listed author) in the most cited papers by researchers granted CNPq fellowships. We found that researchers from Pharmacology had the best performance for all of the parameters analysed, followed by those in Biochemistry. There was great variability in scientific productivity within the PQ 1A level in all of the sub-fields of BS, but not within the other levels (1B, 1C and 1D). Analysis of the most cited papers of PQ 1(A-D) researchers in Pharmacology revealed that the citations of researchers in the 1C and 1D levels were associated with publications with their senior supervisors, whereas those in the 1B level were less connected with their supervisors in comparison to those in 1A. Taken together, these findings suggest that the scientific performance of PQ 1A researchers in BS is not homogenous. In our opinion, parameters such as the most cited papers without the involvement of Ph.D. and/or post-doctoral supervisors should be used to make decisions regarding any given researcher's fellowship award level.

Copper attenuates early and late biochemical alterations induced by inorganic mercury in young rats.

Mercury (Hg), a divalent metal, produces adverse effects predominantly in the renal and central nervous systems. The aim of this study was to determine the effectiveness of copper (Cu) in prevention of mercuric mercury (Hg2+)-mediated toxic effects as well as the role metallothioneins (MT) play in this protective mechanism in young rats. Wistar rats were treated subcutaneously with saline (Sal) or CuCl2.2H2O (Cu 2.6 mg/kg/day) from 3 to 7 days old and with saline or HgCl2 (Hg 3.7 mg/kg/day) from 8 to 12 days old. The experimental groups were (1) Sal-Sal, (2) Cu-Sal, (3) Sal-Hg, and (4) Cu-Hg. MTs and metal contents were determined at 13 and 33 days of age. Porphobilinogen synthase (PBG-synthase) activity as well as renal and hepatic parameters were measured at 33 days. At 13 day, Hg2+ exposure increased hepatic MT, Hg, zinc (Zn) and iron (Fe) levels, in kidney elevated Cu and Hg and decreased renal Fe concentrations, accompanied by elevated blood Hg levels. At 33 days, Hg2+ exposure inhibited renal PBG-synthase activity, increased serum urea levels and lowered Fe and Mg levels. Copper partially prevented the rise in blood Hg and liver Fe noted at 13 days; and completely blocked urea rise and diminished renal PBG-synthase activity inhibition at 33 days. In 13-day-old rats, Cu exposure redistributed the Hg in the body, decreasing hepatic and blood levels while increasing renal levels, accompanied by elevated renal and hepatic MT levels in Hg2+-exposed animals. These results suggest that hepatic MT might bind to hepatic and blood Hg for transport to the kidney in order to be excreted. ABBREVIATIONS: MT: metallothioneins; PBG-synthase: porphobilinogen synthase.

Antioxidant and mercury chelating activity of Psidium guajava var. pomifera L. leaves hydroalcoholic extract.

Mercury (Hg) is widely distributed in the environment and is known to produce several adverse effects in organisms. The aim of the present study was to examine the in vitro antioxidant activity and Hg chelating ability of the hydroalcoholic extract of Psidium guajava leaves (HEPG). In addition, the potential protective effects of HEPG against Hg(II) were evaluated using a yeast model (Saccharomyces cerevisiae). HEPG was found to exert significant antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenger and inhibition of lipid peroxidation induced by Fe(II) assays in a concentration-dependent manner. The extract also exhibited significant Hg(II) chelating activity. In yeast, Hg(II) induced a significant decrease in cell viability. In contrast, HEPG partially prevented the fall in cell viability induced by Hg(II). In conclusion, HEPG exhibited protective effects against Hg(II)-mediated toxicity, which may be related to both antioxidant and Hg(II)-chelating activities.

Acute mercury exposition of virgin, pregnant, and lactating rats: Histopathological kidney and liver evaluations.

This work investigated the effects of mercury chloride (HgCl2 ) acute exposure on virgin, pregnant and lactating rats by determination of renal and hepatic morphological and ultrastructural parameters and the expression of oxidative stress and stress tolerance markers, due to kidney and liver are the organs that more accumulate inorganic mercury. Adult Wistar rats virgin (90 days old), pregnant (18th gestation day) and lactating (7th lactation day) were injected once with HgCl2 (5 mg/kg) or saline (controls). We observed that HgCl2 exposure of virgin rats caused significant inflammatory infiltration and severe morphological variations, like glomeruli atrophy, dilatation of Bowman's capsule, tubular degeneration and hepatocytes alteration. Moreover, virgin rats presented mitochondrial modification, important oxidative stress and increase in stress tolerance proteins at both kidney and liver level, compared with virgin controls. In detail, virgin rats exposed to HgCl2 presented significantly elevated level of inducible nitric oxide synthase, heat shock protein 27 and glucose regulated proteins 75 expressions at both renal tubular and hepatocytes level, respect untreated virgin rats. Interestingly, pregnant and lactating rats exposed to HgCl2 presented weak renal and liver morphological alterations, showing weak inflammatory infiltration and no significant difference in structural mitochondrial transmembrane protein, oxidative stress markers and stress tolerance proteins expressions respect controls (virgin, pregnant and lactating rats). Although, both control and HgCl2 -exposed pregnant and lactating rats showed renal glomeruli greater in diameter respect virgin rats. In conclusion, we believe that virgin rats are more sensitive to HgCl2 toxicity respect pregnant and lactating rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1500-1512, 2017.

Free radical scavenging in vitro and biological activity of diphenyl diselenide-loaded nanocapsules: DPDS-NCS antioxidant and toxicological effects.

Selenium compounds, such as diphenyl diselenide (DPDS), have been shown to exhibit biological activity, including antioxidant effects. However, the use of DPDS in pharmacology is limited due to in vivo pro-oxidative effects. In addition, studies have shown that DPDS-loaded nanocapsules (DPDS-NCS) have greater bioavailability than free DPDS in mice. Accordingly, the aim of this study was to investigate the antioxidant properties of DPDS-NCS in vitro and biological activity in mice. Our in vitro results suggested that DPDS-NCS significantly reduced the production of reactive oxygen species and Fe(II)-induced lipid peroxidation (LPO) in brain. The administration of DPDS-NCS did not result in death or change the levels of endogenous reduced or oxidized glutathione after 72 hours of exposure. Moreover, ex vivo assays demonstrated that DPDS-NCS significantly decreased the LPO and reactive oxygen species levels in the brain. In addition, the highest dose of DPDS-NCS significantly reduced Fe(II)- and sodium nitroprusside-induced LPO in the brain and Fe(II)-induced LPO in the liver. Also, δ-aminolevulinate acid dehydratase within the brain was inhibited only in the highest dose of DPDS-NCS. In conclusion, our data demonstrated that DPDS-NCS exhibited low toxicity in mice and have significant antioxidant characteristics, indicating that nanoencapsulation is a safer method of DPDS administration.

Zinc and N-acetylcysteine modify mercury distribution and promote increase in hepatic metallothionein levels.

This study investigated the ability of zinc (Zn) and N-acetylcysteine (NAC) in preventing the biochemical alterations caused by mercury (Hg) and the retention of this metal in different organs. Adult female rats received ZnCl2 (27mg/kg) and/or NAC (5mg/kg) or saline (0.9%) subcutaneously and after 24h they received HgCl2 (5mg/kg) or saline (0.9%). Twenty-four hours after, they were sacrificed and analyses were performed. Hg inhibited hepatic, renal, and blood δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, decreased renal total thiol levels, as well as increased serum creatinine and urea levels and aspartate aminotransferase activity. HgCl2-exposed groups presented an important retention of Hg in all the tissues analyzed. All pre-treatments demonstrated tendency in preventing hepatic δ-ALA-D inhibition, whereas only ZnCl2 showed this effect on blood enzyme. Moreover, the combination of these compounds completely prevented liver and blood Hg retention. The exposure to Zn and Hg increased hepatic metallothionein levels. These results show that Zn and NAC presented promising effects against the toxicity caused by HgCl2.

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 (5.0mg/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 (5.0mg/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.