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.

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.

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.