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.

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.

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.

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.

IQ alteration induced by lead in developed and underdeveloped/developing countries: A systematic review and a meta-analysis.

The aim of this study was to evaluate the effects of Pb exposure on full-scale IQ score in pediatric subjects. Following PRISMA guidelines, the data from January 2010 to April 2020 were systematically searched and collected on electronic databases (PubMed, Scopus, and Embase). The eligibility criteria included cross-sectional, cohort, and case-control studies that were published in English, from 2010 to 2020, that analyzed the blood Pb levels of pediatric subjects (0-19 years) and possible changes in the full-scale IQ score. In this study, 2174 scientific papers were collected from three electronic databases. From those, 726 were duplicates and 1421 were excluded because they did not meet the eligibility criteria, resulting in a total of 27 papers, from which, seven were used to perform the meta-analysis. The 27 scientific papers systematically selected for this study were separated by the country where the study was realized in developed and underdeveloped/developing countries. In the underdeveloped/developing countries the blood Pb levels are higher and showed a greater variation (1.30-11.66 µgPb/dL of blood) than in countries with higher development index (0.57-4.80 µgPb/dL of blood). The full-scale IQ score are inversely proportional to the blood Pb values, and it is possible to see that in the underdeveloped/developing countries the full-scale IQ score showed lower values and greater variation (59.2-111) compared to the individuals from developed countries (91.9-114.5). In conclusion, it was observed that blood Pb levels alter the full-scale IQ score. Thus, policies for the prevention of environmental contamination and the reduction of Pb exposure must be taken, mainly, in underdeveloped/developing countries.