Ultrasmall MnSe Nanoparticles as T1-MRI Contrast Agents for In Vivo Tumor Imaging.

Magnetic resonance imaging (MRI) has excellent potential in the clinical monitoring of tumors because it can provide high-resolution soft tissue imaging. However, commercial contrast agents (CAs) used in MRI still have some problems such as potential toxicity to the human body, low relaxivity, and a short MRI acquisition window. In this study, ultrasmall MnSe nanoparticles are synthesized by living Staphylococcus aureus cells. The as-prepared MnSe nanoparticles are monodispersed with a uniform particle size (3.50 ± 0.52 nm). Due to the ultrasmall particle size and good water solubility, the MnSe nanoparticles exhibit in vitro high longitudinal relaxivity properties (14.12 ± 1.85 mM-1·s-1). The CCK-8 colorimetric assay, histological analysis, and body weight results show that the MnSe nanoparticles do not have appreciable toxicity on cells and organisms. Besides, the MnSe nanoparticles as T1-MRI CAs offer a long MRI acquisition window to tumor imaging (∼7 h). This work provides a promising T1-MRI CA for clinical tumor imaging and a good reference for the application of functional MnSe nanoparticles in the biomedicine field.

Food Sources of Selenium and Its Relationship with Chronic Diseases.

Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials.

Maternal supplementation of organic selenium during gestation improves sows and offspring antioxidant capacity and inflammatory status and promotes embryo survival.

Selenium (Se) is an essential trace element in humans and sows, having a biological function mediated in part by its incorporation into selenoproteins. This study was conducted to investigate the effects of maternal 2-hydroxy-4-methylselenobutanoic acid (HMSeBA), an organic Se source, on reproductive performance, antioxidant capacity and inflammatory status of sows and their offspring. Forty-three Landrace × Yorkshire sows were randomly allocated to receive one of the following three diets during gestation: control diet (control, basal diet, n = 15), sodium selenite (Na2SeO3) supplemented diet (Na2SeO3, basal diet + Na2SeO3 at 0.3 mg Se per kg, n = 13), and HMSeBA supplemented diet (HMSeBA, basal diet + HMSeBA at 0.3 mg Se per kg, n = 15). Blood samples of sows and piglets, placentas and piglet liver samples were analyzed for selenium status, antioxidant capacity and inflammatory cytokines. Results showed that, as compared to the control group, HMSeBA supplementation increased the number of born alive piglets and plasma concentrations of total selenium and selenoprotein P in both sows and piglets. Besides, the activities of antioxidant enzymes in the blood of sows, umbilical cord and piglets, placentas and piglets' liver were increased by dietary HMSeBA supplementation as compared to the control group, while malondialdehyde concentration (p < 0.05) was decreased in the blood of sows, umbilical cord and newborn piglets. In addition, maternal HMSeBA intake during gestation up-regulated antioxidant-related selenoprotein gene expression in the placenta (GPx2, GPx3, p < 0.05) and in the liver of newborn piglets (GPx1, GPx2, GPx3, TXNRD2, p < 0.05). Moreover, as compared to the control group, sows and newborn piglets in the Na2SeO3 and HMSeBA groups had a lower serum interleukin-6 (p < 0.05) concentration, and placentas in the HMSeBA group had lower IL-1ß, IL-6 and IL-8 gene expression (p < 0.05). In conclusion, maternal supplementation of HMSeBA during pregnancy improved antioxidant capacities and reduced the inflammation level in mater, placenta, and fetus. This finding may highlight the important role of selenoproteins (especially GPXs) in preventing negative consequences of over-production of free radicals and inflammatory cytokines during gestation and at births.

Comparison of three oral selenium compounds in cancer patients: Evaluation of differential pharmacodynamic effects in normal and malignant cells.

BACKGROUND: Selenium (Se) compounds have demonstrated therapeutic synergism in combination with anticancer treatments whilst reducing normal tissue toxicities in a range of experimental models. While reduction in some toxicities of chemotherapy and radiation has been confirmed in randomised clinical trials, they have not been powered to evaluate improved anticancer efficacy. A lack of data on the clinical potencies of the main nutritionally-relevant forms of Se and the relationship between their pharmacokinetic (PK) profiles and pharmacodynamic (PD) effects in cancer patients has hampered progress to date. The primary objective of this study was to determine the dose and form of Se that can be most safely and effectively used in clinical trials in combination with anti-cancer therapies. STUDY METHODS: In a phase I randomised double-blinded study, the PD profile of sodium selenite (SS), Se-methylselenocysteine (MSC) and seleno-l-methionine (SLM) were compared in two cohorts of 12 patients, one cohort with chronic lymphocytic leukaemia (CLL) and the other with solid malignancies. All 24 patients were randomised to receive 400 µg of elemental Se as either SS, MSC or SLM, taken orally daily for 8 weeks. PD parameters were assessed before, during and 4 weeks after Se compound exposure in plasma and peripheral blood mononuclear cells (PBMCs). RESULTS: No significant sustained changes were observed in plasma concentrations of vascular endothelial growth factor-α (VEGF-α), expression of proteins associated with endoplasmic reticulum stress (the unfolded protein response) or in intracellular total glutathione in PBMCs, in either disease cohort or when grouped by Se compound. CONCLUSIONS: At the 400 µg dose level no substantial changes in PD parameters were noted. Extrapolating from pre-clinical data, the dose examined in this cohort was too low to achieve the Se plasma concentration (≥ 5 µM) expected to elicit significant PD effects. Recruitment of a subsequent cohort at higher doses to exceed this PK threshold is planned.

Tumor-facing hepatocytes significantly contribute to mild hyperthermia-induced targeting of rat liver metastasis by PLGA-NPs.

The effect of mild hyperthermia (MHT) on nanoparticle (NP) accumulation in rat model liver metastasis and the contribution of neoplastic and non-neoplastic cells were characterized. CdSe/ZnS QD-doped poly(lactic-co-glycolic acid) (PLGA) NPs (155 ±â€¯10 nm) were delivered via the ileocolic vein to metastatic livers 15 min after localized MW irradiation (1 min, 41 °C) or in normothermia (37 °C, NT). Quantitative analysis of tissue sections by confocal fluorescence microscopy 1 h after NP injection showed no NP tumor accumulation in NT. On the contrary, MHT increased NP association with tumor, compared to normal tissue. Counterstaining of specific markers showed that the MHT effect is due to an increased NP endocytosis not only by tumor cells, but also by hepatocytes at the growing tumor edge and, to a minor extent, by tumor-associated macrophages. High-NP capturing hepatocytes, close to the tumor, may be a relevant phenomenon in MHT-induced increased targeting of NPs to liver metastasis, influencing their therapeutic efficacy.

H2Se Induces Reductive Stress in HepG2 Cells and Activates Cell Autophagy by Regulating the Redox of HMGB1 Protein under Hypoxia.

Rationale: Selenium has been shown to have chemotherapeutic effects against cancer. However, the anti-cancer mechanism of selenium is not fully understood, and the role of hydrogen selenide (H2Se), which is a common metabolite of dietary selenium compounds, has not been elucidated due to the lack of detection methods. In this study, we revealed a new anti-cancer mechanism of selenite with the help of a H2Se fluorescent probe. Methods: HepG2 cells were cultured under a simulated tumor hypoxic microenvironment. The H2Se and H2O2 levels were detected by fluorescent probes in living cells and in mice. Autophagic and apoptotic proteins were detected by Western blotting. The redox of HMGB1 protein were analyzed by non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis. Results: After pharmacological doses of Na2SeO3 treatment of HepG2 cells under hypoxic conditions, high levels of H2Se were produced before cell death. The H2Se accumulation resulted in reductive stress instead of oxidative stress, which was induced by Na2SeO3 treatment under normoxic conditions. Furthermore, H2Se targeted the HMGB1 protein and induced cell autophagy. H2Se could interrupt the disulfide bond in HMGB1 and promote its secretion. The reduced HMGB1 outside the cells stimulated cell autophagy by inhibiting the Akt/mTOR axis. Here, autophagy played a dual role, i.e., mild autophagy inhibited apoptosis, while excessive autophagy led to autophagy-associated cell death. Conclusions: These results show that H2Se plays a key role during HepG2 cell death induced by selenite. Our findings reveal a new anti-cancer mechanism of selenite and provide a new research area for selenium studies.

Histological analysis of rat prostate under exogenous testosterone and low dose of oral selenium administration / Histología de la próstata de ratón influenciada por testosterona y la dosis supranutricional de selenio / Histologia da próstata de rato sob influência de testosterona exógena e dose supranutricional de selênio

Objective: to verify selenium effectiveness in maintenance of prostate tissue architecture. Method: experimental study using 20 adult 90-day-old male rats divided into the following groups: TG, 05 animals that received injectable testosterone; TSG, 05 animals that received injectable testosterone and weekly doses of selenium by gavage; CG1, 05 intact animals; CG2, 05 animals that received saline injection and saline by gavage. Results: characteristic architecture was found in tissue samples from animals of CG with cubic/prismatic secretory epithelium surrounded by fibro-muscular stroma. Animals of TG showed an increase in prostatic epithelium height, increase in the number of blood vessels in stroma and presence of proliferative lesions. Proliferative lesions were also found in tissue samples from animals of TSG, besides having improve in epithelial height, as seen in TG. Conclusion: it is concluded that selenium at this concentration has no effectiveness in modulating morphology of prostatic tissue of adult rats.(AU)

Objetivo: verificar la eficacia del selenio en mantener la morfología tisular. Método: estudio experimental, utilizando 20 ratones machos adultos (5 animales/grupo), divididos en: TG, recibieron testosterona inyectable; TSG, recibieron testosterona inyectable y dosis semanales de selenio por gavado; CG1, animales intactos; CG2, recibieron solución salina inyectable y por gavado. Resultados: una arquitectura característica fue encontrada en las muestras tisulares de los animales del CG, con epitelio cúbico/prismático envuelto por estroma fibro-muscular. En los animales del TG la próstata presentó un epitelio con células más altas, un aparente aumento en el número de vasos sanguíneos estromais, además de la presencia de lesiones proliferativas. También se encontraron lesiones proliferativas en las muestras tisulares de los animales del TSG, además de presentar mayor altura del epitelio, como vistas en TG. Conclusión: se concluye así que el Selenio, en esta concentración, parece no ser eficaz en la protección contra las modificaciones promovidas por la administración de T exógena en ratas adultas.(AU)

Objetivo: verificar a eficácia do selênio na manutenção da morfologia tecidual prostática. Métodos: estudo experimental, utilizando 20 ratos machos adultos, divididos em: TG, 05 animais que receberam testosterona injetável; TSG, 05 animais que receberam testosterona injetável e doses semanais de selênio por gavagem; CG1, 05 animais intactos; CG2, com 05 animais que receberam solução salina injetável e por gavagem. Resultados: uma arquitetura característica foi encontrada nas amostras teciduais dos animais do CG, com epitélio cúbico/prismático envolvido por estroma fibro-muscular. Nos animais do TG a próstata apresentou um epitélio com células mais altas, um aparente aumento no número de vasos sanguíneos no estroma, além da presença de lesões proliferativas. Também foram encontradas lesões proliferativas nas amostras teciduais dos animais do TSG, além de apresentarem maior altura do epitélio, como vistas no TG. Conclusão: conclui-se assim, que o Selênio, nesta concentração, parece não ser eficaz na proteção contra as modificações promovidas pela administração de T exógena em ratos adultos.(AU)

Enhanced bioreduction-responsive diselenide-based dimeric prodrug nanoparticles for triple negative breast cancer therapy.

Efficient drug accumulation in tumor is essential for chemotherapy. We developed redox-responsive diselenide-based high-loading prodrug nanoparticles (NPs) for targeted triple negative breast cancer (TNBC) treatment. Method: Redox-responsive diselenide bond (Se-Se) containing dimeric prodrug (PTXD-Se) was synthesized and co-precipitated with TNBC-targeting amphiphilic copolymers to form ultra-stable NPs (uPA-PTXD NPs). The drug loading capacity and redox-responsive drug release behavior were studied. TNBC targeting effect and anti-tumor effect were also evaluated in vitro and in vivo.Results: On-demand designed paclitaxel dimeric prodrug could co-precipitate with amphiphilic copolymers to form ultra-stable uPA-PTXD NPs with high drug loading capacity. Diselenide bond (Se-Se) in uPA-PTXD NPs could be selectively cleaved by abnormally high reduced potential in tumor microenvironment, releasing prototype drug, thus contributing to improved anti-cancer efficacy. Endowed with TNBC-targeting ligand uPA peptide, uPA-PTXD NPs exhibited reduced systemic toxicity and enhanced drug accumulation in TNBC lesions, thus showed significant anti-tumor efficacy both in vitro and in vivo. Conclusion: The comprehensive advantage of high drug loading, redox-controlled drug release and targeted tumor accumulation suggests uPA-PTXD NPs as a highly promising strategy for effective TNBC treatment.

Selenium in Radiation Oncology-15 Years of Experiences in Germany.

Introduction: Se measurement and supplementation in radiation oncology is a controversial issue. The German Working Group Trace Elements and Electrolytes in Oncology (AKTE) has conducted a number of studies on this issue, which are summarized in this review. Strategies have been tested and developed, aiming to stratify the patients with a potential need for supplemental Se and how best to monitor Se supplementation with respect to health effects and risks. Methods: We analyzed blood and tissue Se-levels of different tumor patients (n = 512). Two randomized phase III clinical studies were conducted for testing a potential radioprotective effect of supplemental Se during radiation therapy in patients with uterine cancer (n = 81) and head and neck tumor patients (n = 39). Results: A relative Se deficit in whole blood or serum was detected in the majority of tumor patients (carcinomas of the uterus, head and neck, lung, rectal or prostate cancer). In prostate cancer, tissue Se concentrations were relatively elevated in the carcinoma centre as compared to the surrounding compartment or as compared to tumor samples from patients with benign prostatic hyperplasia. Adjuvant Se supplementation successfully corrected Se-deficiency in the patients analyzed and decreased radiotherapy-induced diarrhea in a randomized study of radiotherapy patients with carcinomas of the uterus. Survival data imply that Se supplementation did not interfere with radiation success. Some positive effects of supplemental Se in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy were noted in a second randomized trial in patients with head and neck cancer. We have not observed any adverse effects of supplemental Se in our studies. Conclusions: Se supplementation yielded promising results concerning radioprotection in tumor patients and should be considered as a promising adjuvant treatment option in subjects with a relative Se deficit.

Hydroxy-selenomethionine: A novel organic selenium source that improves antioxidant status and selenium concentrations in milk and plasma of mid-lactation dairy cows.

This study aimed to evaluate the effect of hydroxy-selenomethionine (HMSeBA), a novel organic selenium (Se) source, on milk performance, antioxidative status, and Se concentrations in the milk and plasma of mid-lactation dairy cows compared with that of sodium selenite (SS). Fifty mid-lactation dairy cows with similar days in milk, milk yield, and parity received the same basal diet containing 0.06 mg of Se/kg of DM. They were assigned to 1 of 5 treatments according to a randomized complete block design: negative control (without Se supplementation), SS supplementation (0.3 mg of Se/kg of DM; SS-0.3) or HMSeBA supplementation (0.1, 0.3, or 0.5 mg of Se/kg of DM: SO-0.1, SO-0.3, and SO-0.5, respectively). The experiment lasted for 10 wk, including a pretrial period of 2 wk. The results indicated that neither Se supplementation nor Se source affected dry matter intake, milk yield, milk composition, or blood biochemical parameters, except for milk fat percentage. Simultaneously, milk fat percentage and milk fat yield increased linearly as the quantity of HMSeBA supplementation was increased. Production of 4% FCM and ECM was elevated linearly as dietary HMSeBA increased. The SO-0.3 group showed higher serum activity of glutathione peroxidase, total antioxidant capacity, and superoxide dismutase than the SS-0.3 group, but malondialdehyde content was not affected by Se source. Furthermore, HMSeBA supplementation linearly increased the activities of serum glutathione peroxidase and superoxide dismutase, but decreased malondialdehyde content. Compared with the SS-0.3 group, the SO-0.3 group showed augmented concentrations of total Se in milk and plasma, and total Se milk-to-plasma concentration ratio. In addition, increasing doses of HMSeBA linearly increased the concentrations of total Se in the milk and plasma. This study demonstrates that HMSeBA improves antioxidant status and increases milk and plasma Se concentrations more effectively than SS, indicating that HMSeBA could replace SS as an effective organic Se source for lactating dairy cows.

Synergistic Effects of SAM and Selenium Compounds on Proliferation, Migration and Adhesion of HeLa Cells.

BACKGROUND/AIM: To determine the antitumor activities and molecular mechanism of selenium compounds in HeLa cells. MATERIALS AND METHODS: Western blotting was used to detect ERK and AKT activation in HeLa cells induced by selenium compounds selenomethionine (SeMet), methylselenocysteine (MeSeCys) and methylseleninic acids (MeSeA). Using MTT, wound-healing and Matrigel adhesion assays, the antitumor effects of SAM and selenium compounds were evaluated in HeLa cells. RESULTS: MeSeA inhibited ERK and AKT signaling pathways and suppressed the proliferation (p<0.05 vs. HeLa control), migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. MeSeCys and SeMet inhibited AKT signaling pathways and the migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. The synergistic action of MeSeA with SAM led to a statistically significant inhibition of proliferation, migration and adhesion of HeLa cells. CONCLUSION: MeSeA, MeSeCys and SeMet exert different antitumor activities by inhibiting ERK and AKT signaling pathways. The combination of MeSeA and SAM exhibited better antitumor effects compared to the other treatments.

Selenium nanoparticles: potential in cancer gene and drug delivery.

In recent decades, colloidal selenium nanoparticles have emerged as exceptional selenium species with reported chemopreventative and therapeutic properties. This has sparked widespread interest in their use as a carrier of therapeutic agents with results displaying synergistic effects of selenium with its therapeutic cargo and improved anticancer activity. Functionalization remains a critical step in selenium nanoparticles' development for application in gene or drug delivery. In this review, we highlight recent developments in the synthesis and functionalization strategies of selenium nanoparticles used in cancer drug and gene delivery systems. We also provide an update of recent preclinical studies utilizing selenium nanoparticles in cancer therapeutics.

Visible light-induced crosslinking and physiological stabilization of diselenide-rich nanoparticles for redox-responsive drug release and combination chemotherapy.

Undesired physiological instability of nanocarriers and premature drug leakage during blood circulation result in compromised therapeutic efficacy and severe side effects, which have significantly impeded the development of nanomedicine. Facile crosslinking of drug-loaded nanocarriers while keeping the potency of site-specific degradation and drug release has emerged as a viable strategy to overcome these drawbacks. Additionally, combination therapy has already shown advantages in inhibiting advanced tumors and life extension than single drug therapy. Herein, three kinds of diselenide-rich polymers were fabricated with distinct hydrophobic side chains. The component effect was interrogated to screen out PEG-b-PBSe diblock copolymer due to its favorable self-assembly controllability and high drug loading of camptothecin (CPT) and doxorubicin (DOX) that had synergistic antitumor property. Facile visible light-induced diselenide metathesis and regeneration was employed to crosslink nanocarriers for the first time. The dual drug-loaded crosslinked micelles (CPT/DOX-CCM) were stable in physiological conditions with minimal drug leakage, possessing extended blood circulation, whereas hand-in-hand dual drug release was significantly accelerated in tumor's redox microenvironments. In vitro cytotoxicity evaluation and in vivo tumor suppression with low dosage drugs further demonstrated the favorable potency of the redox-responsive nanoplatform in tumor combination chemotherapy.

Antimutagenic Effects of Selenium-Enriched Polysaccharides from Pyracantha fortuneana through Suppression of Cytochrome P450 1A Subfamily in the Mouse Liver.

Both selenium (Se) and polysaccharides from Pyracantha fortuneana (Maxim.) Li (PFPs) (P. fortuneana) have been reported to possess antioxidative and immuno-protective activities. Whether or not Se-containing polysaccharides (Se-PFPs) have synergistic effect of Se and polysaccharides on enhancing the antioxidant and immune activities remains to be determined. We previously reported that polysaccharides isolated from Se-enriched P. fortuneana (Se-PFPs) possessed hepatoprotective effects. However, it is not clear whether or not they have anti-mutagenic effects. In the present study, we compared and evaluated anti-mutagenic effects of Se-PFPs at three concentrations (1.35, 2.7 and 5.4 g/kg body weight) with those of PFPs, Se alone or Se + PFPs in mice using micronucleus assay in bone marrow and peripheral blood as well as mitomycin C-induced chromosomal aberrations in mouse testicular cells. We also elucidated the underlying mechanism. Our results demonstrated that Se-PFPs inhibited cyclophosphamide (CP)-induced micronucleus formation in both bone marrow and peripheral blood, enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in mouse liver, and reduced the activity and expression of cytochrome P450 1A (CYP4501A) in mouse liver in a dose-dependent manner. In addition, we found that the anti-mutagenic potential of Se-PFPs was higher than those of PFPs, Se alone or Se + PFPs at the same level. These results suggest that the anti-mutagenic potential of Se-PFPs may be mediated through the inhibition of the activity and expression of CYP4501A. This study indicates that application of Se-PFPs may provide an alternative strategy for cancer therapy by targeting CYP1A family.

Current Knowledge on the Importance of Selenium in Food for Living Organisms: A Review.

Selenium is one of the elements classified within the group of micronutrients which are necessary in trace amounts for the proper functioning of organisms. Selenium participates in the protection of cells against excess H2O2, in heavy metal detoxification, and regulation of the immune and reproductive systems as well. It also ensures the proper functioning of the thyroid gland. Selenium induces the occurrence of the selenoprotein synthesis process involved in the antioxidant defense mechanism of the organism. Recent years have brought much success in the studies on selenium. Anticarcinogenic properties of selenium against some cancers have been reported. Supplementation is increasingly becoming a solution to this problem. A large number of different supplementation methods are promoting studies in this area. Slight differences in the selenium content can result in excess or deficiency, therefore supplementation has to be done carefully and cautiously.

A nanosensor for in vivo selenol imaging based on the formation of Au-Se bonds.

Selenol is a key metabolite of Na2SeO3 and plays an important role in many physiological and pathological processes. The real-time monitoring of selenol is of scientific interest for understanding the anti-cancer mechanism of Na2SeO3. Based on selenol's ability to specifically break AuS bonds and form more stable AuSe bonds on the surfaces of gold nanoparticles (AuNPs), we developed a novel near-infrared fluorescent nanosensor (Cy5.5-peptide-AuNPs) for detecting selenol. The nanosensor exhibited rapid response to selenol with high selectivity and sensitivity, and it was successfully used to image changes in the selenol level in HepG2 cells during Na2SeO3-induced apoptosis. Moreover, in vivo fluorescence imaging of selenol was obtained from H22 tumor-bearing mice injected with both the nanosensor and sodium selenite. The results showed that the tumor cell apoptosis induced by Na2SeO3 is correlated with high-level of selenol under hypoxic conditions. We believe that this nanosensor could serve as a powerful tool for monitoring selenol and exploring the physiological function of selenol in a variety of physiological and pathological contexts and that the probe-designed strategy will provide a new platform for research on relevant selenium chemistry.

Biodistribution and Pharmacokinetic Study of 3,3' Diseleno Dipropionic Acid (DSePA), A Synthetic Radioprotector, in Mice.

BACKGROUND AND OBJECTIVES: 3,3' Diseleno dipropionic acid (DSePA), a synthetic compound has been shown to have radioprotective activity, especially as a lung radioprotector. In this study, the pharmacokinetics and biodistribution of DSePA in MX-1 tumour bearing SCID mice were evaluated. METHODS: Twenty SCID mice were administered DSePA (50 mg/kg bodyweight) by oral gavage following which four animals each were sacrificed at 15, 30 min, 1, 2 and 4 h. Blood and tissue samples were collected for determination of DSePA concentration by graphite furnace atomic absorption spectrometry (GFAAS) method. The control group (n = 4) was administered sterile water and sacrificed at 4 h. RESULTS: Peak plasma concentration (C max) of 2.7 µg/ml was observed at 15 min which returned to near baseline (baseline = 0.6 µg/ml) at 1 h following drug administration. Biphasic pharmacokinetics characterized by rapid distribution phase and a slower elimination phase were observed. Highest maximal concentration (C max) of the drug was observed in lung (19.2 µg/g at 30 min) followed by intestine (14.64 µg/g at 15 min) and kidney (12.96 µg/g at 15 min). There was negligible uptake in tumor tissue and no uptake in brain. CONCLUSIONS: DSePA has a favorable pharmacokinetic profile which makes it a potentially good candidate for further development as a radioprotective agent.

Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice.

Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.

Effects of nanocrystalline PbSe on hematopoietic system and bone marrow micronucleus rate of rats.

OBJECTIVE: To investigate the effect of lead selenide nanocrystals on hematopoietic system and bone marrow micronucleus rate of rats. METHOD: Specific pathogen free SD rats were randomly divided into 4 groups (8 rats in each group), and injected with of 0 (control group), 10 (low dose group), 20 (middle dose group), 30 mg/kg (high dose group) nanocrystalline PbSe, respectively. Seven weeks after injection, the blood was taken from rats for routine index detection; the number of micronucleus cells per 1000 polychromatic erythrocyte from bone marrow was counted. RESULTS: White blood cell (WBC), lymphocyte (LYM) count in low dose group rats, and WBC, LYM, granulocyte (GRN), monocytes (MOD) counts in high dose group significantly increased compared to those of control group. LYM% ratio decreased while GRN% ratio increased along with the increase of exposure dosage. Compared with those of the control group, levels of erythrocyte mean corpuscular volume (MCV) in low dose group, hemoglobin (HGB), red blood cell specific volume (HCT), MCV in middle dose group and red blood cell (RBC), HGB, HCT, MCV in high dose group, were markedly decreased. Red blood cell distribution width (RDW), blood platelet (PLT) levels in three exposure groups of were higher than those in control group. Marrow micronucleus test results showed that, the micronucleus rate rise in mid dose and high dose group compared with the control group, suggesting that nanocrystalline PbSe has genetic toxicity on rats. CONCLUSIONS: Nano PbSe can lead to changes in blood routine index and bone marrow micronucleus rate, and its toxicity was positively related to the dosage.

Characterization of selenium-enriched mycelia of Catathelasma ventricosum and their antihyperglycemic and antioxidant properties.

This is the first report concerning the selenium enrichment of Catathelasma ventricosum mycelia. The selenium-containing proteins present in selenium-enriched mycelia (Se-MC) were identified using size-exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS). The selenium-containing amino acids liberated by hydrolysis of these proteins were identified using anion exchange-ICP-MS. Se-MC was found to contain selenoproteins with molecular weights ranging from 1.7 to 60.5 kDa. The main selenium-containing amino acids within them were selenomethionine and selenocysteine. Furthermore, Se-MC possessed excellent antihyperglycemic and antioxidant properties. Se-MC normalized biochemical parameters like insulin level, blood glucose level, body weight, and antioxidant enzyme activity in streptozocin-induced diabetic mice. It also inhibited the α-amylase and α-glucosidase activities present in in vitro gastric and intestinal models. In conclusion, Se-MC has the potential to serve as a dietary supplement of selenium, an antioxidant, or an ingredient for the formulation of nutraceuticals.