On the chemical radioprotection by organic selenium compounds in vivo.
Explore the source record for details and available documents.
SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
2-month-old male rats kept on a standard laboratory diet containing 0.06 microgram Se/g dry weight were found to be more sensitive to the toxic action of selenite than female rats of corresponding age. This sex-dependent difference was not found in 20-day-old animals. Previous s.c. administration of 1 mumol of selenium in the form of sodium selenite lowered the sensitivity of male rats to the toxic effects of selenite. The protective effect of this dose persisted for 18 days. A similar protective action against the lethal effects of selenite in adult male rats was exhibited by sodium selenate, selenomethionine, and dimethylselenide, all in an amount equal to 1 mumol of selenium; pretreatment with trimethylselenonium iodide showed only an insignificant mortality decrease. Three days intake of deionized water with an addition of 0.1 or 1.0 microgram selenium/ml also protected male rats against lethal doses of selenite. Peroral pretreatment of adult females did not decrease their sensitivity to the lethal effects of selenite.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The influence of sodium selenite, selenomethionine and sodium selenite with tocopherols in combination on the survival of cryopreserved erythrocytes was investigated. Percent hemolysis is marked decreased after a three-hour incubation of the whole blood with addition of selenomethionine as well as sodium selenite with tocopherole in combination before cryopreservation. The protective effect is attributed to the antioxydative and membrane stabilizing effectiveness of selenium and tocopherol.
The mutagenicities of selenate (SeO2/4-) and selenite (SeO2/3-) were determined by two bacterial assay systems: Kada's rec-assay and Ames's Salmonella test. In both assays, these compounds were found to be weak mutagens. In the Salmonella test, selenate (0.05 revertants/nmole) and selenite (0.2 revertants/nmole) gave rise to base-pair substitution.
Following administration by gavage [75Se]selenate and [75Se]selenite were absorbed from the gastrointestinal tract of fathead minnows (Pimephales promelas) at 94 and 80% efficiency, respectively. Approximately 12% of the [75Se]selenate administered by i.p. injection was eliminated via the urine, and across the gill within 2 hr. The urine was the primary route of elimination followed by the gill. The bile contained significantly lower amounts of 75Se than that eliminated either across the gill or in the urine. The mucus is capable of binding significant amounts of 75Se. Dietary pretreatment with selenite reduced the retention of a subsequent [75Se]selenite dose administered by gavage.
The main binding protein for 109Cd was metallothionein after in vitro incubation of various tissue cytosol preparations obtained from rats supplemented with zinc. The exception was heart cytosol where the label was associated with higher molecular weight proteins. The metallothionein-bound 109Cd was sensitive to trithiomolybdate and moved too higher molecular weight proteins, presumably because of the creation of new stronger ligands by the association of thiomolybdate with these proteins. The 109Cd binding was affected by selenate, selenite, and selenide while molybdate, sulphate, and thiosulphate were ineffective. It is proposed that thiomolybdates should be investigated for use in the therapy of in vivo cadmium toxicity because they can remove the accumulated metal from metallothionein.
Eight commercially available selenides, a selenol, and selenourea were examined for substrate activity with purified pig liver flavin-containing monooxygenase (FMO). While none of the aromatic heterocyclic selenides tested showed detectable activity, all dialkyl- and alkylaryl-selenides free from ionic groups stimulated NADPH- and FMO-dependent oxygen uptake. With limiting substrate the molar ratio of oxygen reduced to selenide added was 1:1. Analysis of products from N-[2-(methylseleno)ethyl]benzamide demonstrated that the selenide was quantitatively oxidized to selenoxide. Further oxidation of either the FMO-generated or synthetic selenoxides was not detected. The dialkyl- and alkylaryl-selenoxides are potent thiol oxidants and reaction rates for the oxidation of thiols by methylphenylselenoxide and N-[2-(methylseleninyl)ethyl]benzamide followed second order kinetics with rate constants from 3-4 x 10(3) M-1 s-1 at pH 7.4, 37 degrees C. The rapid oxidation of thiols by these selenoxides demonstrates that the oxidation of selenides to selenoxides catalyzed by crude tissue preparations can be measured by following selenide-dependent oxidation of thiocholine by the procedure described earlier for the oxidation of thiourea (WXA Guo and D. M. Ziegler, 1991, Anal. Biochem. 198, 143-148). Activity measurements by this procedure indicated that the oxidation of dialkyl selenides by rat, guinea pig, or pig liver microsomes was catalyzed primarily by a monooxygenase with the properties of FMO. However, from 20 to 40% of the microsome-catalyzed oxidation of selenides bearing aryl substituents was sensitive to N-benzylimidazole, suggesting that P450-dependent monooxygenases also contribute, at least in part, to the oxidation of these xenobiotics.
Using steady state/time resolved spectroscopic and electrochemical techniques the spectroscopic and photophysical studies were made on a novel synthesized selenophene compound SeP in nonpolar methylcyclohexane (MCH), polar aprotic acetonitrile (ACN) and polar protic ethanol (EtOH) solvents at the ambient temperature as well as at 77 K. Both from the studies on unimolecular and bimolecular photoprocesses this selenophene compound was found to possess several electronic levels, 1Bb, 1La, 1Lb (all are of pi pi* nature and 1Lb is hidden within 1La band envelop like the characteristics of most of the acenes) and 1(nO pi*) state arising due to carbonyl oxygen atom. In polar ACN environment this nO pi* state disappears because it moves within the envelop of intense 1La band due to large destabilization. Large overlapping of different band systems within the 1La band of SeP was confirmed from the observed depolarization effect. The lack of phosphorescence of SeP both in MCH and EtOH rigid glassy matrix at 77 K has been inferred due to large vibronic interactions between closely lying triplets of the corresponding 1nO pi* and 1Lb states. From the bimolecular investigations, it reveals that SeP acts as a good electron donor in presence of the well known electron acceptor 9 cyanoanthracene (9CNA). Transient absorption spectra measured by laser flash photolysis technique demonstrate the formation of ion-pair when the acceptor is excited. From the analysis of the fluorescence quenching data it seemingly indicates that the major contribution in the diminution of the fluorescence intensity of the acceptor 9CNA in presence of SeP is not only due to the photoinduced electron transfer (ET) but also originates from static type (instantaneous) quenching processes along with external heavy atom effect. The possibility of occurrence of photoinduced ET reaction in Marcus inverted region is hinted.
Activation of Jun-N-kinases (JNK) is stimulated by diverse agents including UV-irradiation, heat shock, tumor necrosis factor and osmotic shock. In the present study we have elucidated the effect of the organoselenium chemopreventive agent 1,4-phenylenebis(methylene)selenocyanate (p-XSC, on UV-mediated JNK activation. Using mouse fibroblasts as a model cell system we found that low concentrations (1-10 microM range) of p-XSC did not affect JNK activity, yet were capable of potentiating JNK activity when administered prior to UV-irradiation. While higher doses of p-XSC have minimal effect on JNK activation, when combined with UV, there is a dose-dependent decrease in JNK activation. Similar to its effects on JNK, p-XSC is a potent inducer of src-related tyrosine kinases. p-XSC mediated changes in JNK activation correlate with its ability to potentiate the association of JNK with p21ras, in a manner similar to that we have previously observed with GTP or sodium vanadate. That p-XSC can modulate JNK activities points to a possible mechanism by which it contributes to the cell's ability to cope with stress.
In liver homogenate the biosynthesis of N-acetylneuraminic acid using N-acetylglucosamine as precursor can be followed stepwise by applying different chromatographic procedures. In this cell-free system 16 metal ions (Zn2+, Mn2+, La3+, Co2+, Cu2+, Hg2+, VO3-, Pb2+, Ce3+, Cd2+, Fe2+, Fe3+, Al3+, Sn2+, Cs+ and Li+) and the selenium compounds, selenium(IV) oxide and sodium selenite, have been checked with respect to their ability to influence a single or possibly several steps of the biosynthesis of N-acetylneuraminic acid. It could be shown that the following enzymes are sensitive to these metal ions (usually applied at a concentration of 1 mmol l-1): N-acetylglucosamine kinase (inhibited by Zn2+ and vandate), UDP-N-acetylglucosamine-2'-epimerase (inhibited by Zn2+, Co2+, Cu2+, Hg2+, VO3-, Pb2+, Cd2+, Fe3+, Cs+, Li+, selenium(IV) oxide and selenite), and N-acetylmannosamine kinase (inhibited by Zn2+, Cu2+, Cd2+ and Co2+). Dose dependent measurements have shown that Zn2+, Cu2+ and selenite are more efficient inhibitors of UDP-N-acetylglucosamine-2'-epimerase than vanadate. As for the N-acetylmannosamine kinase inhibition, a decreasing inhibitory effect exists in the following order Zn2+, Cd2+, Co2+ and Cu2+. In contrast, La3+, Al3+ and Mn2+ (1 mmol l-1) did not interfere with the biosynthesis of N-acetylneuraminic acid. Thus, the conclusion that the inhibitory effect of the metal ions investigated cannot be regarded as simply unspecific is justified.
The monograph program of the International Agency for Research of on Cancer has evaluated many trace elements for their carcinogenicity to humans. Five groups of compounds were considered human carcinogens: arsenic and arsenic compounds, beryllium and beryllium compounds, cadmium and cadmium compounds, hexavalent chromium compounds, and nickel compounds. Antimony trioxide, cobalt and cobalt compounds, lead and inorganic lead compounds, methylmercury compounds, and metallic nickel were considered possibly carcinogenic to humans. Antimony trisulfide, trivalent chromium compounds, metallic chromium, ferric oxide, organolead compounds, metallic mercury, inorganic mercury compounds, selenium and selenium compounds, and titanium dioxide were not classifiable. Trace elements studied to a limited extent include copper, manganese, tin, vanadium, and zinc. Among the problems are the lack of relevant data, the definition of active species, the extrapolation of the results of experimental studies to humans, the methodological problems of epidemiologic studies, and the possible anticarcinogenic activity of some trace elements.
Antioxidant properties of selenium producing a protective barrier against free radicals play an important role in numerous metabolic and immunologic processes associated with oxidation-reduction reactions which take place during intracellular digestion of phagocyted bacteria. The aim of our study was to examine the properties of an organic compound of selenium, 4-(o-tolilo)-selenosemicarbazide of p-chlorobenzoic acid in terms of its retention in organs, effect on erythropoesis and phagocytic abilities of neutrophiles as well as antioxidant properties in neutrophiles tested with NBT test. This compound as well as inorganic sodium selenate was given to Swiss mice at the dose of 10(-3) g Se/kg for the period of 10 days. The concentrations of selenium in livers of mice treated with sodium selenate and selenosemicarbazide were found to be higher than in controls (18.7 micrograms lg-1 and 23.2 micrograms lg-1 vs. 12 micrograms lg-1, respectively). Analysis of blood cells count has shown a significant decrease in neutrophile levels in both groups treated with selenium. The influence of selenium compounds on phagocytosis and especially NBT test has been determined (3.8% of positive cells in the controls vs. 2.2% and 0.9% in the groups treated with sodium selenate and selenosemicarbazide, respectively). Our preliminary investigations suggest that selenosemicarbazides are biologically active compounds and can modify neutrophile functions.
The effect of different inorganic and organic selenium compounds on the nucleic acid synthesis in culture of human carcinoma ovary cells was studied. The rate of synthesis was determined by the incorporation of 3H-thymidine in the DNA and 3H-uridine in the RNA. Selenium compounds in the concentration to 1 mg/ml inhibited the nucleic acid synthesis in human tumour cells. The level of nucleic acid inhibition depends on the concentration of examined compounds. The tetravalent selenium compounds possessed the most pronounced cytotoxic effect.