Selenium-Derivative Compounds: A Review of New Perspectives in the Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most prevalent types of dementia, affecting millions of older people worldwide. AD is stimulating efforts to develop novel molecules targeting its main features associated with a decrease in acetylcholine levels, an increase in oxidative stress and depositions of amyloid-ß (Aß) and tau protein. In this regard, selenium-containing compounds have been demonstrated as potential multi-targeted compounds in the treatment of AD. These compounds are known for their antioxidant and anticholinesterase properties, causing a decrease in Aß aggregation. OBJECTIVE: In this review, we approach structure-activity relationships of each compound, associating the decrease of ROS activity, an increase of tau-like activity and inhibition of AChE with a decrease in the self-aggregation of Aß. METHODS: We also verify that the molecular descriptors apol, nHBAcc and MlogP may be related to optimized pharmacokinetic properties for anti-AD drugs. RESULTS: In our analysis, few selenium-derived compounds presented similar molecular features to FDA-approved drugs. CONCLUSION: We suggest that unknown selenium-derived molecules with apol, nHBAcc and MlogP like FDA-approved drugs may be better successes with optimized pharmacokinetic properties in future studies in AD.

Combination of selol nanocapsules and magnetic hyperthermia hinders breast tumor growth in aged mice after a short-time treatment.

Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.

Drugs for preventing lung cancer in healthy people.

BACKGROUND: This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer. OBJECTIVES: To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer. DATA COLLECTION AND ANALYSIS: Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach. MAIN RESULTS: In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little to no difference in lung cancer incidence (RR 1.11, 95% CI 0.80 to 1.54; 1 RCT, 17448 participants; high-certainty evidence) and lung cancer mortality (RR 1.09, 95% CI 0.72 to 1.66; 1 RCT, 17448 participants; high-certainty evidence) and increases the risk for grade 1 to 2 dermatitis (RR 1.16, 95% CI 1.04 to 1.31; 1 RCT, 17448 participants; high-certainty evidence) and for alopecia (RR 1.28, 95% CI 1.07 to 1.53; 1 RCT, 17448 participants; high-certainty evidence). The combination of vitamins A, C, E + selenium + zinc results in little to no difference in lung cancer incidence (RR 0.64, 95% CI 0.28 to 1.48; 1 RCT, 12741 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes.

3-(4-Chlorophenylselanyl)-1-methyl-1H-indole promotes recovery of neuropathic pain and depressive-like behavior induced by partial constriction of the sciatic nerve in mice.

3-(4-Chlorophenylselanyl)-1-methyl-1H-indole (CMI) is an organoselenium compound that presents antioxidant activity, antinociceptive, anti-inflammatory and antidepressive-like effect in mice in previous studies conducted by our research group. In this study, we evaluate the anti-allodynic, anti-hyperalgesic and antidepressant-like effects of CMI on partial sciatic nerve ligation (PSNL) in male adult Swiss mice (25-35 g) as well as the involvement of oxidative stress in these effects. Mice underwent PSNL surgery and after 4 weeks they were treated with CMI (10 mg/kg, intragastric route [i.g.]) or vehicle. The treatment with CMI (10 mg/kg, i.g.) reversed the increased the percentage of response to Von-Frey Hair (VFH) stimulation, decreased the latency time to nociceptive response in the hot-plate test, increased immobility time in the forced swimming test (FST) and decreased groomings activity in the splash test, all induced by PSNL. Additionally, CMI also reversed increased the levels of reactive oxygen species (ROS) and lipid peroxidation in cortex and hippocampus and plasmatic levels of corticosterone in mice, induced by PSNL. Results demonstrate that CMI reversed behavioral and biochemical alterations in the dyad pain-depression induced by PSNL and possibly modulation of oxidative system.

The selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole reverses depressive-like behavior induced by acute restraint stress in mice: modulation of oxido-nitrosative stress and inflammatory pathway.

RATIONALE AND OBJECTIVES: Stress-induced alterations in oxidative and inflammatory parameters have been implicated in the pathophysiology of mood disorders. Based on the antioxidant and anti-inflammatory properties of the selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole (CMI), we assessed its ability to reverse depression-like behavioral alterations, neuroinflammation, and oxidative imbalance induced by acute restraint stress. METHODS: Mice submitted to restraint for 240 min received CMI (1 or 10 mg/kg, orally) 10 min after the end of the stress induction. Behavioral and biochemical tests were carried out after further 30 min. RESULTS: Restraint-induced depression-like behavior in the tail suspension test (TST), splash test, and new object exploration test was reversed by CMI. None of the treatments evoked locomotor alteration. In addition, CMI abrogated restraint-induced increases in plasma levels of corticosterone and in markers of oxidative stress and impaired superoxide dismutase and catalase activity in the prefrontal cortex (PFC) and hippocampus (HC). CMI also blocked stress-induced downregulation of mRNA levels of glucocorticoid receptor and brain-derived neurotrophic factor and upregulation of nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis alpha, indoelamine-2,3-dioxygenase, and glycogen synthase kinase 3 beta in PFC and HC. CONCLUSIONS: These preclinical results indicate that administration of selenium-containing compounds might help to treat depression associated with inflammation and oxidative stress. Graphical abstract ᅟ.

3-(4-Chlorophenylselanyl)-1-methyl-1H-indole, a new selenium compound elicits an antinociceptive and anti-inflammatory effect in mice.

Several pathologies, such as pain and inflammation, are modulated by different pathways, making it necessary to develop drugs capable of modulating different pathways. Based on that, we investigated the antinociceptive and anti-inflammatory effect of 3-(4-chlorophenylselanyl)-1-methyl-1H-indole (CMI), as well as the systems involved in these actions. This study evaluated the antinociceptive and anti-inflammatory effects of CMI [0.0001-10 mg/kg administered intragastrically (i.g.)] in the formalin, glutamate, hot plate, ear edema induced by croton oil and paw edema induced by formalin tests. In addition, to investigate the mechanism of action, mice were pre-treated with antagonists of adenosinergic, monoaminergic and opioid systems before administration of CMI. The selenium-containing compound decreased the paw licking and biting time in the formalin and glutamate tests, increased the response latency in hot plate test, without ambulatory changes, evaluated in the open field test. CMI was able to reduce both paw and ear edema induced by formalin and croton oil, respectively. Additionally the antinociceptive effect of CMI (0.01 mg/kg) was blocked when mice were pretreated with the antagonists: SCH23390 [D1-receptor antagonist, 0.05 mg/kg, intraperitoneally (i.p.)], WAY100635 (5-HT1A-receptor antagonist, 0.7 mg/kg, i.p.), ondansetron (5-HT3-receptor antagonist, 0.5 mg/kg, i.p.), ketanserin (5-HT2A/2C-receptor antagonist, 0.3 mg/kg, i.p.), naloxone (non-selective antagonist 1 mg/kg, i.p.), caffeine (non-selective antagonist, 3 mg/kg, i.p.) and prazosin (α1-receptor antagonist, 0.15 mg/kg, i.p). These results demonstrate that the antinociceptive effect of CMI is mediated by monaminergic, opioidergic and adenosinergic modulations and can be a promising molecule capable of modulating different pathways for the treatment of pain and inflammation.

Drugs for preventing lung cancer in healthy people.

BACKGROUND: This is an updated version of the original review published in Issue 2, 2003. Some studies have suggested a protective effect of antioxidant nutrients on lung cancer. Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta-carotene and a lower risk of lung cancer. OBJECTIVES: To determine whether vitamins, minerals and other potential agents, alone or in combination, reduce incidence and mortality from lung cancer in healthy people. SEARCH METHODS: For this update we have used a search strategy adapted from the design in the original review. The following electronic databases have been searched up to December 2011: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). References included in published studies and reviews were also screened. SELECTION CRITERIA: Included studies were randomised controlled clinical trials comparing different vitamins, mineral supplements or supplements with placebo, administered to healthy people with the aim of preventing lung cancer. DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials to be included in the review, assessed the methodological quality of each trial and extracted data using a standardised form. For each study, relative risk and 95% confidence limits were calculated for dichotomous outcomes and pooled results were calculated using the random-effect model. MAIN RESULTS: In the first version of this review four studies were included; in this review update, an additional five studies have been included. Four studies included only males and two only females; two studies included only participants considered at high risk, namely smokers or exposed to asbestos, and one study included people deficient in many micronutrients. Six studies analysed vitamin A, three vitamin C, four vitamin E, one selenium supplements, and six studied combinations of two or more products. All the RCTs included in this review were classified as being of low risk of bias.For people not at high risk of lung cancer and compared to placebo, none of the supplements of vitamins or minerals or their combinations resulted in a statistically significant difference in lung cancer incidence or mortality, except for a single study that included 7627 women and found a higher risk of lung cancer incidence for those taking vitamin C but not for total cancer incidence, but that effect was not seen in males or when the results for males and females were pooled.For people at high risk of lung cancer, such as smokers and those exposed to asbestos and compared to placebo, beta-carotene intake showed a small but statistically significant higher risk of lung cancer incidence, lung cancer mortality and for all-causes mortality. AUTHORS' CONCLUSIONS: There is no evidence for recommending supplements of vitamins A, C, E, selenium, either alone or in different combinations, for the prevention of lung cancer and lung cancer mortality in healthy people. There is some evidence that the use of beta-carotene supplements could be associated with a small increase in lung cancer incidence and mortality in smokers or persons exposed to asbestos.

Barium selenate supplementation and its effect on intramammary infection in pasture-based dairy cows.

A significant proportion of cattle receive inadequate dietary Se because of its low content in soils and pastures of various regions of the world. Several economically important diseases in dairy cows, such as mastitis, have been associated with Se deficiency. The objective of this study was to evaluate the effect of a single injection of a long-acting form of Se at drying off on the risk and incidence rate of new intramammary infections and on milk somatic cell count in the subsequent lactation in pasture-based dairy cows. Forty-nine Chilean Holstein-Friesian cows were fed a diet containing <0.05 mg of Se/kg of ration dry matter. During the dry period, cows were allocated to 1 of 2 groups, a supplemented (n=24) group treated with a single subcutaneous injection of barium selenate 2 mo before calving and a control group (n=25) that remained unsupplemented. Duplicate foremilk samples were aseptically collected within 6 d after calving and every 2 wk until drying-off for bacteriological culture. Milk samples were also collected monthly for somatic cell count evaluation. Blood samples were collected before treatment and at 30, 90, 180, and 270 d after treatment for analysis of blood glutathione peroxidase (GPx) activity. The activity of glutathione peroxidase was higher in supplemented cows 30 d after the injection until the end of the study. The risk and incidence rate of new intramammary infections was not affected by supplementation. A progressive increase in somatic cell count was observed throughout lactation, but there was no effect of supplementation. In conclusion, a one-time injection of barium selenate 2 mo before calving in these pasture-based dairy cows did not affect udder health in the subsequent lactation, indicating that Se basal intake was adequate for preventing subclinical mastitis in pasture-based cows in southern Chile.

Papilomatosis reticulada y confluente familiar / Reticulated and confluent familiar papillomatosis

La papilomatosis reticulada y confluente (Gougerot-Carteaud) es una entidad infrecuente caracterizada por la presencia de pápulas pardas queratósicas que coalescen formando placas de aspecto reticulado en la periferia. La afectación familiar es extremadamente rara. Se presenta un caso de PRC en 2 hermanos (AU)

Papilomatosis reticulada y confluente familiar / Reticulated and confluent familiar papillomatosis

La papilomatosis reticulada y confluente (Gougerot-Carteaud) es una entidad infrecuente caracterizada por la presencia de pápulas pardas queratósicas que coalescen formando placas de aspecto reticulado en la periferia. La afectación familiar es extremadamente rara. Se presenta un caso de PRC en 2 hermanos (AU)

Papilomatosis reticulada y confluente (Gougerot-Carteaud): respuesta terapéutica a sulfuro de selenio y revisión / Reticulated and confluent papillomatosis (Gougerot-Carteaud): response to selenium sulfide

La papilomatosis reticulada y confluente (Gougerot-Carteaud) es una entidad poco frecuente que se carateriza por la presencia de papulas pardas queratósicas que coalescen formando placas de aspecto reticulado en la periferia, cuyas localizaciones mas frecuentes son nuca, axilas, tronco anterior y zona intermamaria. Presentamos un caso que respondió favorablemente al tratamiento con sulfuro de selenio. Se realiza una revisión del tema (AU)