Antioxidant defence mechanisms: From the beginning to the end (of the beginning)

When life first evolved on Earth, there was little oxygen in the atmosphere. Evolution of antioxidant defences must have been closely associated with the evolution of photosynthesis and of O₂-dependent electron transport mechanisms. Studies with mice lacking antioxidant defences confirm the important roles of MnSOD and transferrin in maintaining health, but show that glutathione peroxidase (GPX) and CuZnSOD are not essential for everyday life (at least in mice). Superoxide can be cytotoxic by several mechanisms: one is the formation of hydroxyl radicals. There is good evidence that OH^· formation occurs in vivo. Other important antioxidants may include thioredoxin, and selenoproteins other than GPX. Nitric oxide may be an important antioxidant in the vascular system. Diet-derived antioxidants are important in maintaining human health, but recent studies employing “biomarkers” of oxidative DNA damage are questioning the “antioxidant” roles of β-carotene and ascorbate. An important area of future research will be elucidation of the reasons why levels of steady-state oxidative damage to DNA and lipids vary so much between individuals, and their predictive value for the later development of human disease.     

Design,synthesis, characterization,antibacterial and antifungal activities of a novel class of 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles

Compound 26 is more potent against Escherichia coli. and 24 is more active against Staphylococcus aureus, β-Heamolytic streptococcus, Vibreo cholerae, Salmonella typhii, and Shigella flexneri than the standard drug ciprofloxacin. Moreover, of all the compounds tested, 26 is more effective against Aspergillus flavus and Mucor, than the standard drug fluconazole.     

Ginseng stem‐leaf saponins in combination with selenium enhance immune responses to an attenuated pseudorabies virus vaccine

Pseudorabies, a herpesvirus infection, is mainly controlled by using attenuated live vaccines. In this study, the effect of ginseng stem and leaf saponins (GSLS) in combination with selenium (Se; in the form of sodium selenite) on vaccination against attenuated pseudorabies virus (aPrV) was evaluated. It was found that GSLS and Se have an adjuvant effect and that a combination of GSLS and Se stimulates significantly enhanced immune responses than does GSLS or Se alone. Following oral administration of GSLS, mice immunized with an attenuated PrV vaccine diluted in Se‐containing physiological saline solution (PSS) provoked a significantly stronger gB‐specific serum antibodies response (IgG, IgG1 and IgG2a), enhanced lymphocyte proliferation and cytolytic activity of NK cells, along with higher production of cytokines (IFN‐γ, IL‐12, IL‐5 and IL‐10) by splenocytes. Notably, the combination of GSLS and Se conferred a much higher resistance to fPrV challenge after immunization of the mice with aPrV vaccine. This study offers convincing experimental evidence that an injection of Se with oral GSLS is a promising adjuvant combination that improves the efficacy of vaccination against PrV and deserves further study regarding improvement of responses to other animal vaccines.     

In vitro assessment of the toxicity of metal compounds

A review of in vitro mutagenesis assessment of metal compounds in mammalian and nonmammalian test systems has been compiled. Prokaryotic assays are ineffective or inconsistent in their detection of most metals as mutagens, with the notable exception of hexavalent chromium. Mammalian assay systems appear to be similarly inappropriate for the screening of metal compounds based upon the limited number of studies that have employed those compounds having known carcinogenic activity. Although of limited value as screening tests for the detection of potentially carcinogenic metal compounds, the well-characterized in vitro mutagenesis systems may prove to be of significant value as a means to elucidate mechanisms of metal genotoxicity.     

Identification of hydrogen selenide and other volatile selenols by derivatization with 1-fluoro-2,4-dinitrobenzene

A procedure is described for the trapping and identification of hydrogen selenide and methyl selenol ( CH3SeH ). The volatile selenols were generated by reducing selenious acid or dimethyldiselenide with Zn dust and hydrochloric acid under a stream of nitrogen and passing into a trapping solution composed of 50 mM 1-fluoro-2,4-dinitrobenzene plus 83 mM sodium bicarbonate in 67% dimethylformamide:33% water. The selenols react rapidly to form stable dinitrophenyl (DNP) selenoethers that can be extracted into benzene; these are easily identified by TLC, HPLC, or mass spectrometry. Hydrogen selenide is trapped in 90-99% yield, primarily as the di-DNP- monoselenide with a trace of di-DNP- diselenide .     

Concurrent quantitative HPLC–mass spectrometry profiling of small selenium species in human serum and urine after ingestion of selenium supplements

Selenium metabolic patterns in the human body originating from five distinct selenium dietary sources, selenate, selenite, selenomethionine (SeMet), methylselenocysteine (MeSeCys) and selenized yeast, were investigated by performing concurrent HPLC–mass spectrometric analysis of human serum and urine. Total selenium and selenium species time profiles were generated by sampling and analyzing serum and urine from volunteers treated with selenium supplements, up to 5 and 24 h following ingestion, respectively. We found that an increase in total serum selenium levels, accompanied by elevated selenium urinary excretion, was the common pattern for all treatments, except for that of selenite supplementation. Selenosugar 1 was a universal serum metabolite in all treatments, indicating that ingested selenium is favorably metabolized to the sugar. Except for selenite and selenized yeast ingestion, these patterns were reflected in the urine time series of the different treatments. Selenosugar 1 was the major selenium species present in urine in all treatments except for the selenate treatment, accounting for about 80% of the identified excreted species within 24 h of ingestion. Furthermore, the urinary metabolite trimethylselenonium ion (TMSe) was detected for the first time in human background serum by using HPLC coupled to elemental and molecular mass spectrometry. The concurrent monitoring of non-protein selenium species in both body fluids provides the relation between bioavailability and excretion of the individual ingested species and of their metabolic products, while the combined use of elemental and molecular mass spectrometry enables the accurate quantitation of structurally confirmed species. This successfully applied approach is anticipated to be a useful tool for more extensive future studies into human selenium metabolism.     

秦巴山区野生多鳞白甲鱼的营养成分分析与评价

选取不同体质量的秦巴山区野生多鳞白甲鱼(Onychostoma macrolepis)20尾,对其肌肉中的常规营养成分、氨基酸和脂肪酸以及微量元素硒的含量进行检测和分析,以期对多鳞白甲鱼的营养价值进行评估。研究结果显示:秦巴山区野生多鳞白甲鱼的粗蛋白和粗脂肪含量分别为17. 37%和1. 76%。谷氨酸含量最高,天冬氨酸和赖氨酸次之,蛋氨酸含量最低,鲜味氨基酸和必需氨基酸分别占氨基酸总量的38. 46%和37. 10%,氨基酸评价指数(EAAI)为77. 00%。野生多鳞白甲鱼二十二碳六烯酸(DHA)和二十碳五烯酸(EPA)的总量为6. 32%,饱和脂肪酸(SFA)和不饱和脂肪酸的比值约为1∶1。肌肉中硒的含量为(0. 058±0. 017)mg/kg。研究结果表明,秦巴山区野生多鳞白甲鱼的营养价值较高,硒含量适中,可以在当地进行进一步产业化开发和推广。     

Expression of a Catalytically Inactive Mutant Form of Glutathione Peroxidase 4 (Gpx4) Confers a Dominant-negative Effect in Male Fertility

The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation. Recently, the cytosolic form of Gpx4 was identified as an upstream regulator of a novel form of non-apoptotic cell death, called ferroptosis, whereas the mitochondrial isoform of Gpx4 was previously shown to be crucial for male fertility. Here, we generated and analyzed mice with a targeted mutation of the active site selenocysteine of Gpx4 (Gpx4_U46S). Mice homozygous for Gpx4_U46S died at the same embryonic stage (E7.5) as Gpx4^−/− embryos as expected. Surprisingly, male mice heterozygous for Gpx4_U46S presented subfertility. Subfertility was manifested in a reduced number of litters from heterozygous breeding and an impairment of spermatozoa to fertilize oocytes in vitro. Morphologically, sperm isolated from heterozygous Gpx4_U46S mice revealed many structural abnormalities particularly in the spermatozoa midpiece due to improper oxidation and polymerization of sperm capsular proteins and malformation of the mitochondrial capsule surrounding and stabilizing sperm mitochondria. These findings are reminiscent of sperm isolated from selenium-deprived rodents or from mice specifically lacking mitochondrial Gpx4. Due to a strongly facilitated incorporation of Ser in the polypeptide chain as compared with selenocysteine at the UGA codon, expression of the catalytically inactive Gpx4_U46S was found to be strongly increased. Because the stability of the mitochondrial capsule of mature spermatozoa depends on the moonlighting function of Gpx4 both as an enzyme oxidizing capsular protein thiols and as a structural protein, tightly controlled expression of functional Gpx4 emerges as a key for full male fertility.