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Skibniewska EM, Skibniewski M. Selenium Content in the Gonads of Healthy Cats ( Felis catus) and Cats with Impaired Homeostasis from the Warsaw Area (Poland). Animals (Basel) 2024; 14:440. [PMID: 38338083 PMCID: PMC10854887 DOI: 10.3390/ani14030440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 01/17/2024] [Accepted: 01/27/2024] [Indexed: 02/12/2024] Open
Abstract
The aim of the present study was to evaluate selenium content in the gonads of healthy cats and those with impaired homeostasis with the use of fluorescence spectroscopy. Higher concentrations of selenium were found in the gonads of the male domestic cats studied. The average content of this element in the testes of healthy males was: 0.59 mg·kg-1 while 0.47 mg·kg-1 wet weight was recorded in the ovaries of females. In the case of individuals with impaired homeostasis, higher values of selenium were found in the ovaries of obese females (0.40 mg·kg-1), while in the case of females with diagnosed malignancy of the mammary gland, the average values were lower and amounted to 0.31 mg·kg-1 wet weight of tissue. On the basis of statistical analysis, significant differences were found according to sex, age, and disturbed homeostasis of the individuals studied. An association was found between low Se in the gonads and obesity, as well as the presence of mammary gland neoplastic lesions. In addition, Se content was found to decrease with age in females, which can reduce resistance to oxidative stress.
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Affiliation(s)
- Ewa M. Skibniewska
- Department of Biology of Animal Environment, Institute of Animal Science, Warsaw University of Life Sciences, Ciszewskiego Street 8, 02-786 Warsaw, Poland
| | - Michał Skibniewski
- Department of Morphological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska Street 159, 02-776 Warsaw, Poland;
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Zhou C, Xiao R, Li M, Wang Q, Cong W, Zhang F. Highland barley grain and soil surveys reveal the widespread deficiency of dietary selenium intake of Tibetan adults living along Yalung Zangpo River. FRONTIERS IN SUSTAINABLE FOOD SYSTEMS 2022. [DOI: 10.3389/fsufs.2022.1007876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
ObjectiveIn order to assess selenium (Se) flux through the soil-plant-human chain in Tibet plateau and explore the reason why local Tibetan adult residents from large scale agricultural production areas in Tibet lacked daily Se intake.MethodsA total of 210 intact highland barley plants and their corresponding cultivated topsoil samples were collected in fields of 14 agricultural counties along Yalung Zangpo River and quantitative dietary data were collected from a cross-sectional survey using a cultural-specific food frequency questionnaire that contained all local Tibetan foods in 2020.ResultsThe mean value of The estimated daily Se dietary intake by each participant was 17.1 ± 1.9 μg/day/adult, the Se concentration in topsoil and highland barley grain were 0.128 ± 0.015 mg/kg and 0.017 ± 0.003 mg/kg, respectively. Although highland barley was the first contributor of dietary Se in local adult residents (34.2%), the dietary Se intake provided by highland barley only about 10% of the EAR value (50 μg/day/adult) currently. A significantly positive relationship was determined between soil total Se content (STSe), available Se content (SASe) and highland barley grain Se content (GSe). The amount of Se in food system depends on a number of soil properties (TOC, pH, clay content, Fe/Mn/Al oxides), climate variables (MAP, MAT) and terrain factor (altitude).ConclusionTo sum up, it can be inferred that the insufficient dietary Se intake of Tibetan adult population living along Yalung Zangbo River is mainly caused by the low Se content in highland barley grain, which was result from the low Se content in cultivated soil. In order to enable adult participants in the present study to achieve recommended dietary Se-intake levels, agronomic fortification with selenised fertilizers applied to highland barley could be a great solution. It is necessary to combine the influencing factors, and comprehensively consider the spatial variation of local soil properties, climatic and topographic conditions, and planting systems.
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Piazza M, Di Cicco M, Pecoraro L, Ghezzi M, Peroni D, Comberiati P. Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome. Biomolecules 2022; 12:556. [PMID: 35454144 PMCID: PMC9024951 DOI: 10.3390/biom12040556] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 03/29/2022] [Accepted: 03/31/2022] [Indexed: 02/04/2023] Open
Abstract
Long Coronavirus disease-19 (COVID-19) refers to the persistence of symptoms related to the infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This condition is described as persistent and can manifest in various combinations of signs and symptoms, such as fatigue, headache, dyspnea, depression, cognitive impairment, and altered perception of smells and tastes. Long COVID-19 may be due to long-term damage to different organs-such as lung, brain, kidney, and heart-caused by persisting viral-induced inflammation, immune dysregulation, autoimmunity, diffuse endothelial damage, and micro thrombosis. In this review, we discuss the potential and biologically plausible role of some vitamins, essential elements, and functional foods based on the hypothesis that an individual's dietary status may play an important adjunctive role in protective immunity against COVID-19 and possibly against its long-term consequences.
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Affiliation(s)
- Michele Piazza
- Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, 37126 Verona, Italy; (M.P.); (L.P.)
| | - Maria Di Cicco
- Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, 56126 Pisa, Italy; (M.D.C.); (P.C.)
| | - Luca Pecoraro
- Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, 37126 Verona, Italy; (M.P.); (L.P.)
| | - Michele Ghezzi
- Allergology and Pneumology Unit, V. Buzzi Children’s Hospital, 20154 Milan, Italy;
| | - Diego Peroni
- Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, 56126 Pisa, Italy; (M.D.C.); (P.C.)
| | - Pasquale Comberiati
- Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, 56126 Pisa, Italy; (M.D.C.); (P.C.)
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Comparison of Serum and Dietary Selenium Levels in Participants with a Positive History of Recurrent Herpes Lesions and Healthy Individuals. BIOMED RESEARCH INTERNATIONAL 2022; 2021:6083716. [PMID: 35005019 PMCID: PMC8741354 DOI: 10.1155/2021/6083716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 11/06/2021] [Accepted: 12/10/2021] [Indexed: 11/25/2022]
Abstract
Aim In this study, we aimed to compare the level of serum and dietary selenium in participants with a positive history of recurrent herpes labial lesions and healthy controls. Materials and Methods This cross-sectional study, conducted during 2020-2021, evaluated the selenium serum level of 40 participants with a positive history of recurrent herpes labial lesions who had referred to Motahhari Laboratory in Shiraz, compared with 38 healthy controls. The selenium level of the serum was assessed by an absorption device, Atomic Graphite Furnace Model FS-240-AAS, made by a US Company. Independent T-test was used to compare the selenium level of males and females. In order to assess the mean age value and gender distribution between the two evaluated groups, the independent T-test and chi-square test were used, respectively. The serum selenium level was compered between both control and test groups. Results The level of serum selenium was not statistically correlated with its dietary level in group 1 (participants with recurrent herpes labialis, P value = 0.18) and group 2 (healthy controls, P value = 0.6). The serum selenium level was compared between groups 1 and 2, which was significantly higher in healthy controls (P value < 0.0001). In contrast, dietary selenium level was not significantly different between patients with a history of herpes labialis and healthy controls (P value = 0.48). The level of serum selenium was not statistically correlated with its dietary level in group 1 (P value = 0.18) and group 2 (P value = 0.6). Conclusion Patients with recurrent herpes labialis had lower serum selenium level as compared to the healthy controls.
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Ermakov VV, Jovanović LN. Biological Role of Trace Elements and Viral Pathologies. GEOCHEMISTRY INTERNATIONAL 2022; 60. [PMCID: PMC8853261 DOI: 10.1134/s0016702922020045] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
The review presents summarized information on a new research avenue in biogeochemistry and geochemical ecology: relationships between the microcosm (viruses) and manifestations of animal and human pathologies. Some aspects of the biological action of selenium, zinc, copper and iodine, their influence on the manifestation and course of viral infections are considered. Attention is focused on the antioxidant, membrane-protective, boosting immunity, hormonal functions of trace elements, and on the antibacterial and antiviral properties of metallic copper and its compounds. The criteria currently applied in assessing the Se status of territories are compared with the incidence of COVID-19 and HIV in the population of the Russian Federation. In some cases, selenium deficiency in the environment is shown to be associated with a higher susceptibility to RNA viral infections. Emphasis is put on the necessity of improving the criteria for assessing the trace element status of territories and further studies in the geochemical ecology of viruses and their role in the biosphere.
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Affiliation(s)
- V. V. Ermakov
- Vernadsky Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia
| | - L. N. Jovanović
- ALFA BK University, Palmira Toljatija, 3, 11070 Belgrade, Serbia
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In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study. Biomolecules 2021; 11:biom11121858. [PMID: 34944502 PMCID: PMC8699537 DOI: 10.3390/biom11121858] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/07/2021] [Accepted: 12/08/2021] [Indexed: 12/24/2022] Open
Abstract
Metal-based drugs represent a rich source of chemical substances of potential interest for the treatment of COVID-19. To this end, we have developed a small but representative panel of nine metal compounds, including both synthesized and commercially available complexes, suitable for medical application and tested them in vitro against the SARS-CoV-2 virus. The screening revealed that three compounds from the panel, i.e., the organogold(III) compound Aubipyc, the ruthenium(III) complex KP1019, and antimony trichloride (SbCl3), are endowed with notable antiviral properties and an acceptable cytotoxicity profile. These initial findings prompted us to perform a computational study to unveil the likely molecular basis of their antiviral actions. Calculations evidenced that the metalation of nucleophile sites in SARS-CoV-2 proteins or nucleobase strands, induced by Aubipyc, SbCl3, and KP1019, is likely to occur. Remarkably, we found that only the deprotonated forms of Cys and Sec residues can react favorably with these metallodrugs. The mechanistic implications of these findings are discussed.
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Tomo S, Saikiran G, Banerjee M, Paul S. Selenium to selenoproteins - role in COVID-19. EXCLI JOURNAL 2021; 20:781-791. [PMID: 34040501 PMCID: PMC8144537 DOI: 10.17179/excli2021-3530] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 04/07/2021] [Indexed: 12/14/2022]
Abstract
The disruption of antioxidant defense has been demonstrated in severe acute respiratory syndrome due to SARS-CoV infection. Selenium plays a major role in decreasing the ROS produced in response to various viral infections. Selenoprotein enzymes are essential in combating oxidative stress caused due to excessive generation of ROS. Selenium also has a role in inhibiting the activation of NF-κB, thus alleviating inflammation. In viral infections, selenoproteins have also been found to inhibit type I interferon responses, modulate T cell proliferation and oxidative burst in macrophages, and inhibit viral transcriptional activators. Potential virally encoded selenoproteins have been identified by computational analysis in different viral genomes like HIV-1, Japanese encephalitis virus (JEV), and hepatitis C virus. This review discusses the role and the possible mechanisms of selenium, selenoproteins, and virally encoded selenoproteins in the pathogenicity of viral infections. Identification of potential selenoproteins in the COVID 19 genome by computational tools will give insights further into their role in the pathogenesis of viral infections.
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Affiliation(s)
- Sojit Tomo
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Gangam Saikiran
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Mithu Banerjee
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
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Guillin OM, Vindry C, Ohlmann T, Chavatte L. Selenium, Selenoproteins and Viral Infection. Nutrients 2019; 11:nu11092101. [PMID: 31487871 PMCID: PMC6769590 DOI: 10.3390/nu11092101] [Citation(s) in RCA: 275] [Impact Index Per Article: 45.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 08/23/2019] [Accepted: 08/27/2019] [Indexed: 02/07/2023] Open
Abstract
Reactive oxygen species (ROS) are frequently produced during viral infections. Generation of these ROS can be both beneficial and detrimental for many cellular functions. When overwhelming the antioxidant defense system, the excess of ROS induces oxidative stress. Viral infections lead to diseases characterized by a broad spectrum of clinical symptoms, with oxidative stress being one of their hallmarks. In many cases, ROS can, in turn, enhance viral replication leading to an amplification loop. Another important parameter for viral replication and pathogenicity is the nutritional status of the host. Viral infection simultaneously increases the demand for micronutrients and causes their loss, which leads to a deficiency that can be compensated by micronutrient supplementation. Among the nutrients implicated in viral infection, selenium (Se) has an important role in antioxidant defense, redox signaling and redox homeostasis. Most of biological activities of selenium is performed through its incorporation as a rare amino acid selenocysteine in the essential family of selenoproteins. Selenium deficiency, which is the main regulator of selenoprotein expression, has been associated with the pathogenicity of several viruses. In addition, several selenoprotein members, including glutathione peroxidases (GPX), thioredoxin reductases (TXNRD) seemed important in different models of viral replication. Finally, the formal identification of viral selenoproteins in the genome of molluscum contagiosum and fowlpox viruses demonstrated the importance of selenoproteins in viral cycle.
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Affiliation(s)
- Olivia M Guillin
- CIRI, Centre International de Recherche en Infectiologie, CIRI, 69007 Lyon, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unité U1111, 69007 Lyon, France
- Ecole Normale Supérieure de Lyon, 69007 Lyon, France
- Université Claude Bernard Lyon 1 (UCBL1), 69622 Lyon, France
- Unité Mixte de Recherche 5308 (UMR5308), Centre national de la recherche scientifique (CNRS), 69007 Lyon, France
| | - Caroline Vindry
- CIRI, Centre International de Recherche en Infectiologie, CIRI, 69007 Lyon, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unité U1111, 69007 Lyon, France
- Ecole Normale Supérieure de Lyon, 69007 Lyon, France
- Université Claude Bernard Lyon 1 (UCBL1), 69622 Lyon, France
- Unité Mixte de Recherche 5308 (UMR5308), Centre national de la recherche scientifique (CNRS), 69007 Lyon, France
| | - Théophile Ohlmann
- CIRI, Centre International de Recherche en Infectiologie, CIRI, 69007 Lyon, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unité U1111, 69007 Lyon, France
- Ecole Normale Supérieure de Lyon, 69007 Lyon, France
- Université Claude Bernard Lyon 1 (UCBL1), 69622 Lyon, France
- Unité Mixte de Recherche 5308 (UMR5308), Centre national de la recherche scientifique (CNRS), 69007 Lyon, France
| | - Laurent Chavatte
- CIRI, Centre International de Recherche en Infectiologie, CIRI, 69007 Lyon, France.
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unité U1111, 69007 Lyon, France.
- Ecole Normale Supérieure de Lyon, 69007 Lyon, France.
- Université Claude Bernard Lyon 1 (UCBL1), 69622 Lyon, France.
- Unité Mixte de Recherche 5308 (UMR5308), Centre national de la recherche scientifique (CNRS), 69007 Lyon, France.
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Moniruzzaman M, Gann ER, Wilhelm SW. Infection by a Giant Virus (AaV) Induces Widespread Physiological Reprogramming in Aureococcus anophagefferens CCMP1984 - A Harmful Bloom Algae. Front Microbiol 2018; 9:752. [PMID: 29725322 PMCID: PMC5917014 DOI: 10.3389/fmicb.2018.00752] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 04/03/2018] [Indexed: 01/05/2023] Open
Abstract
While viruses with distinct phylogenetic origins and different nucleic acid types can infect and lyse eukaryotic phytoplankton, “giant” dsDNA viruses have been found to be associated with important ecological processes, including the collapse of algal blooms. However, the molecular aspects of giant virus–host interactions remain largely unknown. Aureococcus anophagefferens virus (AaV), a giant virus in the Mimiviridae clade, is known to play a critical role in regulating the fate of brown tide blooms caused by the pelagophyte Aureococcus anophagefferens. To understand the physiological response of A. anophagefferens CCMP1984 upon AaV infection, we studied the transcriptomic landscape of this host–virus pair over an entire infection cycle using a RNA-sequencing approach. A massive transcriptional response of the host was evident as early as 5 min post-infection, with modulation of specific processes likely related to both host defense mechanism(s) and viral takeover of the cell. Infected Aureococcus showed a relative suppression of host-cell transcripts associated with photosynthesis, cytoskeleton formation, fatty acid, and carbohydrate biosynthesis. In contrast, host cell processes related to protein synthesis, polyamine biosynthesis, cellular respiration, transcription, and RNA processing were overrepresented compared to the healthy cultures at different stages of the infection cycle. A large number of redox active host-selenoproteins were overexpressed, which suggested that viral replication and assembly progresses in a highly oxidative environment. The majority (99.2%) of annotated AaV genes were expressed at some point during the infection cycle and demonstrated a clear temporal–expression pattern and an increasing relative expression for the majority of the genes through the time course. We detected a putative early promoter motif for AaV, which was highly similar to the early promoter elements of two other Mimiviridae members, indicating some degree of evolutionary conservation of gene regulation within this clade. This large-scale transcriptome study provides insights into the Aureococcus cells infected by a giant virus and establishes a foundation to test hypotheses regarding metabolic and regulatory processes critical for AaV and other Mimiviridae members.
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Affiliation(s)
- Mohammad Moniruzzaman
- Department of Microbiology, The University of Tennessee, Knoxville, Knoxville, TN, United States.,Monterey Bay Aquarium Research Institute (MBARI), Moss Landing, CA, United States
| | - Eric R Gann
- Department of Microbiology, The University of Tennessee, Knoxville, Knoxville, TN, United States
| | - Steven W Wilhelm
- Department of Microbiology, The University of Tennessee, Knoxville, Knoxville, TN, United States
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Casas E, Cai G, Kuehn LA, Register KB, McDaneld TG, Neill JD. Association of Circulating Transfer RNA fragments with antibody response to Mycoplasma bovis in beef cattle. BMC Vet Res 2018. [PMID: 29534724 PMCID: PMC5851088 DOI: 10.1186/s12917-018-1418-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Background High throughput sequencing allows identification of small non-coding RNAs. Transfer RNA Fragments are a class of small non-coding RNAs, and have been identified as being involved in inhibition of gene expression. Given their role, it is possible they may be involved in mediating the infection-induced defense response in the host. Therefore, the objective of this study was to identify 5′ transfer RNA fragments (tRF5s) associated with a serum antibody response to M. bovis in beef cattle. Results The tRF5s encoding alanine, glutamic acid, glycine, lysine, proline, selenocysteine, threonine, and valine were associated (P < 0.05) with antibody response against M. bovis. tRF5s encoding alanine, glutamine, glutamic acid, glycine, histidine, lysine, proline, selenocysteine, threonine, and valine were associated (P < 0.05) with season, which could be attributed to calf growth. There were interactions (P < 0.05) between antibody response to M. bovis and season for tRF5 encoding selenocysteine (anticodon UGA), proline (anticodon CGG), and glutamine (anticodon TTG). Selenocysteine is a rarely used amino acid that is incorporated into proteins by the opal stop codon (UGA), and its function is not well understood. Conclusions Differential expression of tRF5s was identified between ELISA-positive and negative animals. Production of tRF5s may be associated with a host defense mechanism triggered by bacterial infection, or it may provide some advantage to a pathogen during infection of a host. Further studies are needed to establish if tRF5s could be used as a diagnostic marker of chronic exposure.
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Affiliation(s)
- Eduardo Casas
- USDA, ARS, National Animal Disease Center, Ames, IA, 50010, USA.
| | - Guohong Cai
- USDA, ARS, National Animal Disease Center, Ames, IA, 50010, USA
| | - Larry A Kuehn
- USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE, 68933, USA
| | | | - Tara G McDaneld
- USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE, 68933, USA
| | - John D Neill
- USDA, ARS, National Animal Disease Center, Ames, IA, 50010, USA
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Awodele O, Popoola T, Rotimi K, Ikumawoyi V, Okunowo W. Antioxidant modulation of nevirapine induced hepatotoxicity in rats. Interdiscip Toxicol 2016; 8:8-14. [PMID: 27486354 PMCID: PMC4961920 DOI: 10.1515/intox-2015-0002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 01/30/2015] [Accepted: 02/22/2015] [Indexed: 11/15/2022] Open
Abstract
HIV/AIDS related mortality has been dramatically reduced by the advent of antiretroviral therapy (ART). However, ART presents with associated adverse effects. One of such adverse effects is hepatotoxicity observed with nevirapine (NVP) containing ART. Since previous studies showed that NVP hepatotoxicity may be due to oxidative stress via generation of oxidative radicals, this study sought to evaluate the protective effects of antioxidants in alleviating NVP induced hepatotoxicity. Rats were divided into 6 groups with 8 animals per group and received doses of the antioxidants jobelyn (10.7 mg/kg/day), vitamin C (8 mg/kg/day), vitamin E (5 mg/kg/day) and/or NVP (6 mg/kg/day) for 60 days. The animals were sacrificed on day 61 by cervical dislocation, blood samples were collected for biochemical and hematological examination. The liver of the sacrificed animals was weighed and subjected to histopathological examination. There was a statistically significant (p<0.05) elevation in MDA level observed in the NVP group as compared with control. The results further showed non-significant decreases in the levels of MDA in the NVP plus antioxidant groups, except vitamin C, when compared with the NVP alone group. Vitamin E and Vitamin E plus C treated groups showed significantly (p<0.05) higher levels of SOD, CAT and GSH. The results also showed statistically significantly (p<0.05) lower levels of ALT and AST in the antioxidant treated groups There was an observed significantly (p<0.05) higher level of TP and urea in the antioxidant treated rats. A significantly (p<0.05) higher white blood cell count was observed in the antioxidant groups. Histopathological assessment of the liver extracted from the rats showed no visible pathology across the groups. Observations from this study suggest a potentially positive modulatory effect of antioxidants and may be indicative for the inclusion of antioxidants in nevirapine containing ART.
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Affiliation(s)
- Olufunsho Awodele
- Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, University of Lagos, PMB 12003, Lagos-Nigeria
| | - Temidayo Popoola
- Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, University of Lagos, PMB 12003, Lagos-Nigeria
| | - Kunle Rotimi
- Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, University of Lagos, PMB 12003, Lagos-Nigeria
| | - Victor Ikumawoyi
- Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, University of Lagos, PMB 12003, Lagos-Nigeria
| | - Wahab Okunowo
- Department of Biochemistry, College of Medicine University of Lagos, PMB 12003, Lagos-Nigeria
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Abd-ElMoemen N, Menshawy A, Negida A, Alaa El-Din M, Kamel A, Farouk AE. Ebola Outbreak in West Africa; Is Selenium Involved? Int J Pept Res Ther 2015. [DOI: 10.1007/s10989-015-9491-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Selenium-Functionalized Molecules (SeFMs) as Potential Drugs and Nutritional Supplements. TOPICS IN MEDICINAL CHEMISTRY 2015. [DOI: 10.1007/7355_2015_87] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
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Pinzone MR, Cacopardo B, Nunnari G. Micronutrients in HIV Infection Without HAART. HEALTH OF HIV INFECTED PEOPLE 2015:271-294. [DOI: 10.1016/b978-0-12-800767-9.00016-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Genome-wide association study of serum selenium concentrations. Nutrients 2013; 5:1706-18. [PMID: 23698163 PMCID: PMC3708345 DOI: 10.3390/nu5051706] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2013] [Revised: 05/02/2013] [Accepted: 05/09/2013] [Indexed: 11/23/2022] Open
Abstract
Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003) in the second stage (WHI). Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11) and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI). Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.
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Kolachi NF, Kazi TG, Afridi HI, Kazi NG, Mughal MA, Khan S. Effects of selenium and zinc status in biological samples of hepatitis C patient after herbal and pharmaceutical supplements. Biol Trace Elem Res 2013; 152:187-94. [PMID: 23412808 DOI: 10.1007/s12011-013-9617-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Accepted: 01/22/2013] [Indexed: 02/05/2023]
Abstract
The use of natural remedies and pharmacological mineral supplements for liver disease treatment has a long history. In present study, the levels of selenium (Se) and zinc (Zn) were determined in biological samples (serum and whole blood) of female hepatitis C patients (n = 132), age ranged 30-45 years, before and after 30 days treatment with herbal/pharmaceutical supplements. For comparative study, 128 age-matched female subjects, residing in the same residential areas and have socioeconomic status, were selected as referents. The Se and Zn in supplements, blood, and sera were determined by atomic absorption spectrometry. It was observed that Zn and Se in blood and serum samples of viral hepatitis C (HCV) patients were reduced in the range of 28.6-39 % and 24-36 %, respectively, as compared to those of referents. After herbal/pharmaceutical supplementations, 20.6-25.0 and 9.15-13.2 % of Zn and 10.6-12.1 and 19.6-21.4 % of Se were enhanced in sera and blood samples of HCV patients, respectively. The resulted data indicated that the levels of Se and Zn in addition to some biochemical parameters were improved in HCV patients after herbal/pharmaceutical supplementation. The effects of both supplements were not significantly different (p > 0.05).
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Affiliation(s)
- Nida F Kolachi
- National Center of Excellence in Analytical Chemistry, University of Sindh, Jamshoro 76080, Pakistan.
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17
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Abstract
Selenium is an essential trace element for humans and other animals that is required in very small amounts for proper growth and functioning. Several selenium compounds have shown promise as cancer chemopreventive and chemotherapeutic agents. However, the negative outcome of the SELECT trial to some extent dampened the enthusiasm of selenium-related drug development. A look at the selenium compounds, their diverse mechanism of action, bioavailability and efficacy based on chemical structure, however, suggests that failure of SELECT that used selenomethionine supplement to prevent prostate cancer was not a failure of selenium compounds as a whole. This is certainly true in regard to therapeutic applications of selenium compounds. This article puts these arguments in perspective, and based on the literature reports, especially several newly developed selenium compounds, emphasizes the importance of selenium in the development of chemopreventive and particularly chemotherapeutic drugs for cancer in near future.
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Flueck WT, Smith-Flueck JM, Mionczynski J, Mincher BJ. The implications of selenium deficiency for wild herbivore conservation: a review. EUR J WILDLIFE RES 2012. [DOI: 10.1007/s10344-012-0645-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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19
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Shen H, Thomas PR, Ensley SM, Kim WI, Loynachan AT, Halbur PG, Opriessnig T. Vitamin E and selenium levels are within normal range in pigs diagnosed with mulberry heart disease and evidence for viral involvement in the syndrome is lacking. Transbound Emerg Dis 2011; 58:483-91. [PMID: 21518323 PMCID: PMC7169668 DOI: 10.1111/j.1865-1682.2011.01224.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Mulberry heart disease (MHD) in pigs is characterized by lesions of acute haemorrhagic myocarditis and myocardial necrosis. The objectives of this study were to determine the levels of vitamin E and selenium and 13 other trace minerals in heart and liver tissues and to determine the prevalence of certain viral infections in heart tissues from MHD-affected and MHD-unaffected pigs and the vitamin E and selenium concentration in feed samples from selected farms with MHD. Based on the pathological examination, 114 pigs were separated into MHD lesion-negative (L-NEG) (n = 57) and MHD lesion-positive (L-POS) (n = 57) groups. Seventy-three samples (40 L-NEG and 33 L-POS) were subjected to chemical analysis, and 66 (32 L-NEG and 34 L-POS) were subjected to PCR detection for viral pathogens. Lower (P < 0.05) levels of myocardial copper, lower (P < 0.05) levels of hepatic magnesium and higher (P < 0.05) levels of myocardial and hepatic sodium were detected in the L-POS cases. Although lower (P < 0.05) levels of hepatic selenium were detected in L-POS group, all were within the normal range. Analysis of feed samples (n = 22) revealed that selenium levels in all the samples were above the legal limit (0.3 ppm) for pigs. Vitamin E levels in all feed samples were above 20 IU/kg. Among the 66 pigs subjected to PCR detection, there were 19, 4, 13, 8, 2 and 1 animals positive for porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, pan-herpes virus, porcine enterovirus, pan-pestivirus and porcine parvovirus, respectively. Clear evidence of viral association with L-POS was lacking.
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Affiliation(s)
- H Shen
- Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, USA
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20
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Yousefi S, Hadadi A, Ostovar A, Noor BE, Rasoolinejad M, Abdolbaghi MH, Khalili H. Protocol of Determining the Effect of Selenium Supplementation on CD4 + T Lymphocyte Count in HIV/AIDS Patients: A Randomized Double Blind Placebo Controlled Trial. ACTA ACUST UNITED AC 2011. [DOI: 10.4236/aid.2011.12003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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21
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Abstract
HIV infection is a global disease that disproportionately burdens populations with nutritional vulnerabilities. Laboratory experiments have shown that selenium has an inhibitory effect on HIV in vitro through antioxidant effects of glutathione peroxidase and other selenoproteins. Numerous studies have reported low selenium status in HIV-infected individuals, and serum selenium concentration declines with disease progression. Some cohort studies have shown an association between selenium deficiency and progression to AIDS or mortality. In several randomized controlled trials, selenium supplementation has reduced hospitalizations and diarrheal morbidity, and improved CD4(+) cell counts, but the evidence remains mixed. Additional trials are recommended to study the effect of selenium supplementation on opportunistic infections, and other HIV disease-related comorbidities in the context of highly active antiretroviral therapy in both developing and developed countries.
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Affiliation(s)
- Cosby A Stone
- School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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22
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Abstract
The immune system requires several essential micronutrients to maintain an effective immune response. HIV infection destroys the immune system and promotes nutritional deficiencies, which further impair immunity. This article reviews the role of several micronutrients (vitamins A, C, E and D, the B vitamins, and minerals, selenium, iron and zinc) that are relevant for maintaining immune function. In addition, the deficiencies of these micronutrients have been associated with faster progression of HIV-1 disease. This review examines the evidence from observational studies of an association between micronutrient status and HIV disease, as well as the effectiveness of micronutrient supplementation on HIV-disease progression, pregnancy outcomes and nutritional status, among others, utilizing randomized clinical trials. Each micronutrient is introduced with a summary of its functions in human physiology, followed by the presentation of studies conducted in HIV-infected patients in relation to this specific micronutrient. Overall findings and recommendations are then summarized.
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Affiliation(s)
- Adriana Campa
- Florida International University, Stempel College of Public Health & Social Work, University Park, HLS-1–337, Miami, FL 33199, USA
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23
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Schomburg L, Köhrle J. On the importance of selenium and iodine metabolism for thyroid hormone biosynthesis and human health. Mol Nutr Food Res 2009; 52:1235-46. [PMID: 18686295 DOI: 10.1002/mnfr.200700465] [Citation(s) in RCA: 158] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The trace elements iodine and selenium (Se) are essential for thyroid gland functioning and thyroid hormone biosynthesis and metabolism. While iodine is needed as the eponymous constituent of the two major thyroid hormones triiodo-L-thyronine (T3), and tetraiodo-L-thyronine (T4), Se is essential for the biosynthesis and function of a small number of selenocysteine (Sec)-containing selenoproteins implicated in thyroid hormone metabolism and gland function. The Se-dependent iodothyronine deiodinases control thyroid hormone turnover, while both intracellular and secreted Se-dependent glutathione peroxidases are implicated in gland protection. Recently, a number of clinical supplementation trials have indicated positive effects of increasing the Se status of the participants in a variety of pathologies. These findings enforce the notion that many people might profit from improving their Se status, both as a means to reduce the individual health risk as well as to balance a Se deficiency which often develops during the course of illness. Even though the underlying mechanisms are still largely uncharacterised, the effects of Se appear to be exerted via multiple different mechanisms that impact most pronounced on the endocrine and the immune systems.
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Affiliation(s)
- Lutz Schomburg
- Institut für Experimentelle Endokrinologie und Endokrinologisches Forschungs-Centrum der Charité EnForCé, Charité Campus Virchow-Klinikum, Charité Universitätsmedizin, Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
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24
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Iqbal S, Kazi TG, Bhanger MI, Akhtar M, Sarfraz RA. Determination of selenium content in selected Pakistani foods. Int J Food Sci Technol 2008. [DOI: 10.1111/j.1365-2621.2006.01447.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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25
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Cooper LT, Rader V, Ralston NVC. The roles of selenium and mercury in the pathogenesis of viral cardiomyopathy. ACTA ACUST UNITED AC 2007; 13:193-9. [PMID: 17673870 DOI: 10.1111/j.1527-5299.2007.06410.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Research on the pathogenesis of nonischemic dilated cardiomyopathy (DCM) has largely been focused on the role of viral pathogens and altered immunity. Trace elements have only rarely been considered; however, clinical observations that trace elements influence cardiovascular disease have been made in populations with extreme dietary deficiency or occupational exposure. Recently, animal models of DCM have been used to explore interactions among trace elements, viral pathogens, and the immune system. Discovery of interactions of trace elements with causes for DCM has heightened awareness of potential contributions of environmental variables to DCM pathogenesis. This article reviews the present knowledge regarding trace elements, in particular selenium and mercury, in the pathogenesis of viral and immune-mediated DCM. Based on recent studies, the authors propose a novel paradigm for the pathogenesis of viral DCM that incorporates trace element imbalance and its interactions with the cellular physiology of viral-induced cardiomyocyte dysfunction.
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Affiliation(s)
- Leslie T Cooper
- Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
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26
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Franklin MR, Moos PJ, El-Sayed WM, Aboul-Fadl T, Roberts JC. Pre- and post-initiation chemoprevention activity of 2-alkyl/aryl selenazolidine-4(R)-carboxylic acids against tobacco-derived nitrosamine (NNK)-induced lung tumors in the A/J mouse. Chem Biol Interact 2007; 168:211-220. [PMID: 17543294 PMCID: PMC1988784 DOI: 10.1016/j.cbi.2007.04.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2007] [Revised: 04/09/2007] [Accepted: 04/10/2007] [Indexed: 11/16/2022]
Abstract
The efficacy of a series of 2-aryl/alkyl selenazolidine-4(R)-carboxylic acids (SCAs) in reducing NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung adenomas in female A/J mice, a model for tobacco-related lung tumorigenesis, has been investigated. With selenazolidines in the diet for 1 month prior to carcinogen administration and during the subsequent 4 months of tumor development, 2-butylSCA, 2-cyclohexylSCA, 2-phenylSCA and 2-oxoSCA were chemopreventive, significantly reducing mean lung tumor numbers from the 10.9 of unsupplemented controls to 4.7, 5.3, 2.8 and 4.7, respectively. When selenazolidine supplementation began three days after carcinogen administration (i.e., post-initiation), 2-butylSCA, 2-cyclohexylSCA, and 2-oxoSCA were chemopreventive. In both regimens, selenocystine was also chemopreventive. In the post-initiation protocol, but with intervention at a precancerous stage (13 days), whole genome expression analysis of lung RNA identified six gene transcripts that weakly correlated with the efficacy of tumor reduction by the four selenocompounds at 4 months. None of these genes were among those identified to be influenced by chemopreventive selenium compounds in human lung cancer cell lines. When supplementation was for 1 month-prior until 3 days-after carcinogen administration, 2-butylSCA, and 2-phenylSCA were chemopreventive but selenocystine was ineffective. Both 2-butylSCA and 2-phenylSCA retained their chemopreventive activity (44% and 40% tumor number reduction, respectively), when the supplementation was shortened and restricted to a pre-initiation period (days -9 to -2). With supplementation spanning 2 days-prior until 3 days-after NNK, reductions in tumor numbers by 2-phenylSCA (26%) and 2-butylSCA (17%) did not achieve statistical significance. Thus, several 2-aryl/alkyl selenazolidines possess chemopreventive activity against NNK-induced lung tumors, and variously demonstrate pre-initiation and post-initiation efficacy.
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Affiliation(s)
- Michael R Franklin
- University of Utah, Department of Pharmacology and Toxicology, Salt Lake City, UT 84112, USA.
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27
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Drain PK, Kupka R, Mugusi F, Fawzi WW. Micronutrients in HIV-positive persons receiving highly active antiretroviral therapy. Am J Clin Nutr 2007; 85:333-45. [PMID: 17284727 DOI: 10.1093/ajcn/85.2.333] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
In HIV-infected persons, low serum concentrations of vitamins and minerals, termed micronutrients, are associated with an increased risk of HIV disease progression and mortality. Micronutrient supplements can delay HIV disease progression and reduce mortality in HIV-positive persons not receiving highly active antiretroviral therapy (HAART). With the transition to more universal access to HAART, a better understanding of micronutrient deficiencies and the role of micronutrient supplements in HIV-positive persons receiving HAART has become a priority. The provision of simple, inexpensive micronutrient supplements as an adjunct to HAART may have several cellular and clinical benefits, such as a reduction in mitochondrial toxicity and oxidative stress and an improvement in immune reconstitution. We reviewed observational and trial evidence on micronutrients in HIV-positive persons receiving HAART to summarize the current literature and suggest future research priorities. A small number of observational studies have suggested that some, but not all, micronutrients may become replete after HAART initiation, and few intervention studies have found that certain micronutrients may be a beneficial adjunct to HAART. However, most of these studies had some major limitations, including a small sample size, a short duration of follow-up, a lack of adjustment for inflammatory markers, and an inadequate assessment of HIV-related outcomes. Therefore, few data are available to determine whether HAART ameliorates micronutrient deficiencies or to recommend or refute the benefit of providing micronutrient supplements to HIV-positive persons receiving HAART. Because micronutrient supplementation may cause harm, randomized placebo-controlled trials are needed. Future research should determine whether HAART initiation restores micronutrient concentrations, independent of inflammatory markers, and whether micronutrient supplements affect HIV-related outcomes in HIV-positive persons receiving HAART.
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Affiliation(s)
- Paul K Drain
- University of Washington School of Medicine, Seattle, WA 98195, USA.
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28
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Bulska E, Wysocka IA, Wierzbicka MLGH, Proost K, Janssens K, Falkenberg G. In Vivo Investigation of the Distribution and the Local Speciation of Selenium inAlliumcepa L. by Means of Microscopic X-ray Absorption Near-Edge Structure Spectroscopy and Confocal Microscopic X-ray Fluorescence Analysis. Anal Chem 2006; 78:7616-24. [PMID: 17105151 DOI: 10.1021/ac060380s] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In this work, microscopic X-ray absorption near-edge structure spectroscopy (mu-XANES) and confocal microscopic X-ray fluorescence analysis (mu-XRF) were used for the in vivo determination of the distribution of total selenium and for the local speciation of selenium in roots and leaves of onion. Selected Allium cepa L. plants were grown hydroponically in a standard medium containing inorganic selenium compounds (selenite or selenate). The measurements were performed in vivo, that is, on living plants without the need for any form of sampling or sample pretreatment and without the necessity for cutting plant tissues into pieces. Distinct energy differences of the XANES spectra of various selenium reference compounds having different oxidation states allow adjusting the excitation energies used for mu-XRF mapping in such a manner that the distribution of selenium in various oxidation states is obtained with a spatial resolution of a few tens of micrometers within the virtual cross section of the onion tissues. We find that the ratio of inorganic to amino acid selenium compounds differs in various subparts of the plant. Detailed in vivo investigation of the distribution of various selenium species in virtual cross sections of root tips and green leaf shows that the selenium transport takes place via different mechanisms, depending on the nature of the selenium compounds originally taken up.
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Affiliation(s)
- Ewa Bulska
- Faculty of Chemistry, Warsaw University, Warsaw, Poland. ebulska@ chem.uw.edu.pl
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29
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Abstract
In an alternate reading frame overlapping the viral envelope gene, HIV-1 has been shown to encoded a truncated glutathione peroxidase (GPx) module. Essential active site residues of the catalytic core regions of mammalian GPx sequences are conserved in the putative viral GPx (vGPx, encoded by the env-fs gene). Cells transfected with an HIV-1 env-fs construct show up to a 100% increase in GPx enzyme activity, and are protected against the loss of mitochondrial transmembrane potential and subsequent cell death induced by exogenous oxidants or mitochondrial reactive oxygen species. An intact vGPx gene was observed to be more common in HIV-1-infected long-term non-progressors, as compared to HIV-1 isolates from patients developing AIDS. An antioxidant/antiapoptotic protective role of the vGPx is also consistent with the observation that -1 frameshifting induced by the HIV-1 env-fs sequence AAAAAGA (which contains a potential "hungry" arginine codon, AGA) increases during arginine deficiency, which has been associated with increased oxidative stress. Under arginine-limited conditions, nitric oxide synthase generates superoxide, which rapidly combines with NO to form peroxynitrite, which can cause activated T-cells to undergo apoptosis. Thus, biosynthesis of the HIV-1 GPx as an adaptive response to low arginine conditions might delay oxidant-induced apoptotic cell death, providing an enhanced opportunity for viral replication.
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Affiliation(s)
- Lijun Zhao
- Office of Research and Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, PO Box 26170, Greensboro, NC 27402-6170, USA
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30
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Xiao L, Zhao L, Li T, Hartle DK, Aruoma OI, Taylor EW. Activity of the dietary antioxidant ergothioneine in a virus gene-based assay for inhibitors of HIV transcription. Biofactors 2006; 27:157-65. [PMID: 17012772 DOI: 10.1002/biof.5520270114] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The "Long Terminal Repeat" (LTR) of HIV-1 is the target of cellular transcription factors such as NF-kappaB, and serves as the promoter-enhancer for the viral genome when integrated in host DNA. Various LTR-reporter gene constructs have been used for in vitro studies of activators or inhibitors of HIV-1 transcription, e.g., to show that antioxidants such as lipoic acid and selenium inhibit NF-kappaB-dependent HIV-1 LTR activation. One such construct is the pHIVlacZ plasmid, with the HIV-1 LTR driving expression of the lacZ gene (encoding beta-galactosidase, beta-gal). Typically, for inhibitor screening, cells transfected with pHIVlacZ are activated using tumor necrosis factor-alpha (TNF-alpha), and the colorimetric o-nitrophenol assay is used to assess changes in beta-gal activity. A variant of this assay was developed as described here, in which LTR activation was induced by pro-fs, a novel HIV-1 gene product encoded via a -1 frameshift from the protease gene. Cotransfection of cells with pHIVlacZ along with a pro-fs construct produced a significant increase in beta-gal activity over controls. L-ergothioneine dose dependently inhibited both TNF-alpha-mediated and pro-fs-mediated increases in beta-gal activity, with an IC50 of about 6 mM. Thus antioxidant strategy involving ergothioneine derived from food plants might be of benefit in chronic immunodeficiency diseases.
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Affiliation(s)
- Lianchun Xiao
- Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA
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31
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Jackson MJ, Dillon SA, Broome CS, McArdle A, Hart CA, McArdle F. Are there functional consequences of a reduction in selenium intake in UK subjects? Proc Nutr Soc 2005; 63:513-7. [PMID: 15831122 DOI: 10.1079/pns2004382] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Dietary Se levels in the UK have fallen over the last 20 years and recent surveys indicate that average Se intakes are 30-40 microg/d, which is well below the current UK reference nutrient intake for adult men (75 microg/d) or women (60 microg/d). Functional consequences of this decline have not been recognised, although epidemiological data suggest it may contribute to increased risk of infections and incidence of some cancers. Previous data have indicated that biochemical changes in Se-dependent proteins occur in otherwise healthy UK subjects given small Se supplements. The current studies have focused on the effect of small Se supplements on the immune response since there is evidence of specific interactions between Se intake and viral replication, and since the potential anti-cancer effects of Se may be mediated by non-antioxidant effects of Se such as changes in immune function. Data indicate that subjects given small Se supplements (50 or 100 microg Se/d) have changes in the activity of Se-dependent enzymes and evidence of improved immune function and clearance of an administered live attenuated virus in the form of poliovirus vaccine. Responses of individual subjects to Se supplements are variable, and current work is evaluating potential explanations for this variability, including genetic variability and pre-existing Se status.
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Affiliation(s)
- Malcolm J Jackson
- Department of Medicine, University of Liverpool, Liverpool L69 3GA, UK.
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32
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Ko WS, Guo CH, Yeh MS, Lin LY, Hsu GSW, Chen PC, Luo MC, Lin CY. Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C. World J Gastroenterol 2005; 11:4697-702. [PMID: 16094713 PMCID: PMC4615414 DOI: 10.3748/wjg.v11.i30.4697] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the extent of micronutrient and oxidative stress in blood and to examine their linkages with viral loads in chronic hepatitis C patients.
METHODS: Hepatitis C virus (HCV)-RNA levels were quantified in the serum from 37 previously untreated patients with chronic hepatitis C. The plasma and erythrocyte micronutrients (zinc, selenium, copper, and iron) were estimated, and malondialdehyde (MDA) contents were determined as a marker to detect oxidative stress. Antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase (GR) activities in blood were also measured. The control group contained 31 healthy volunteers.
RESULTS: The contents of zinc (Zn), and selenium (Se) in plasma and erythrocytes were significantly lower in hepatitis C patients than in the controls. On the contrary, copper (Cu) levels were significantly higher. Furthermore, plasma and erythrocyte MDA levels, and the SOD and GR activities in erythrocytes significantly increased in hepatitis C patients compared to the controls. However, the plasma GPX activity in patients was markedly lower. Plasma Se (r = -0.730, P < 0.05), Cu (r = 0.635), and GPX (r = -0.675) demonstrated correlations with HCV-RNA loads. Significant correlation coefficients were also observed between HCV-RNA levels and erythrocyte Zn (r = -0.403), Se (r = -0.544), Cu (r = 0.701) and MDA (r = 0.629) and GR (r = 0.441).
CONCLUSION: The levels of Zn, Se, Cu, and oxidative stress (MDA), as well as related anti-oxidative enzymes (GR and GPX) in blood have important impact on the viral factors in chronic hepatitis C. The distribution of these parameters might be significant biomarkers for HCV.
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Affiliation(s)
- Wang-Sheng Ko
- Department of Food and Nutrition, Hung Kuang University, Taichung, Taiwan, China
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33
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Su G, Min W, Taylor EW. An HIV-1 encoded peptide mimics the DNA binding loop of NF-kappaB and binds thioredoxin with high affinity. Mutat Res 2005; 579:133-48. [PMID: 16054658 DOI: 10.1016/j.mrfmmm.2005.02.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2004] [Revised: 02/16/2005] [Accepted: 02/16/2005] [Indexed: 10/25/2022]
Abstract
Pro-fs is a human immunodeficiency virus type 1 (HIV-l)-encoded putative selenoprotein, predicted by a theoretical analysis of the viral genome; it is potentially expressed by a -1 frameshift from the protease coding region. Pro-fs has significant sequence similarity to the DNA binding loop of nuclear factor kappa B (NF-kappaB), which is known to bind thioredoxin (Trx). We hypothesize that the putative HIV-1 pro-fs gene product functions by mimicry of NF-kappaB via binding to Trx. The hypothesis was tested in vitro by co-immunoprecipitation and GST-pull down assays, using a purified mutant pro-fs protein, in which the two potential selenocysteine residues were mutated to cysteines, in order to permit expression in bacteria. Both experiments showed that pro-fs binds to human wild type Trx (Trx-wt) with high affinity. Mutation of the two conserved cysteine residues in the Trx active site redox center to serine (Ser) (Trx-CS) weakened but failed to abolish the interaction. In pro-fs-transfected 293T cells, using confocal microscopy and fluorescence resonance energy transfer (FRET), we have observed that pro-fs localizes in cell nuclei and forms oligomers. Upon stimulation by phorbol 12-myristate 13-acetate (PMA), Trx translocates into cell nuclei. Significant FRET efficiency was detected in the nuclei of PMA-stimulated 293T cells co-expressing fluorescence-tagged pro-fs and Trx-wt or Trx-CS. These results indicate that in living cells the double cysteine mutant of pro-fs binds to both Trx and Trx-CS with high affinity, suggesting that Trx-pro-fs binding is a structurally-specific interaction, involving more of the Trx molecule than just its active site cysteine residues. These results establish the capacity for functional mimicry of the Trx binding ability of the NF-kappaB/Rel family of transcription factors by the putative HIV-1 pro-fs protein.
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Affiliation(s)
- Guoping Su
- Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2352, USA.
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34
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Sirichakwal PP, Puwastien P, Polngam J, Kongkachuichai R. Selenium content of Thai foods. J Food Compost Anal 2005. [DOI: 10.1016/j.jfca.2003.10.010] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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35
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Broome CS, McArdle F, Kyle JAM, Andrews F, Lowe NM, Hart CA, Arthur JR, Jackson MJ. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr 2004; 80:154-62. [PMID: 15213043 DOI: 10.1093/ajcn/80.1.154] [Citation(s) in RCA: 233] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Dietary selenium intakes in many countries, including the United Kingdom, are lower than international recommendations. No functional consequences of these lower intakes have been recognized, although experimental studies suggest that they might contribute to reduced immune function, increased cancer incidence, and increased susceptibility to viral disease. OBJECTIVE The objective was to assess whether administration of small selenium supplements to otherwise healthy UK subjects leads to functional changes in immune status and the rates of clearance and mutation of a picornavirus: live attenuated polio vaccine. DESIGN Twenty-two adult UK subjects with relatively low plasma selenium concentrations (<1.2 micromol/L, approximately 60% of those screened) received 50 or 100 microg Se (as sodium selenite) or placebo daily for 15 wk in a double-blind study. All subjects received an oral live attenuated poliomyelitis vaccine after 6 wk and enriched stable (74)Se intravenously 3 wk later. RESULTS Selenium supplementation increased plasma selenium concentrations, the body exchangeable selenium pool (measured by using (74)Se), and lymphocyte phospholipid and cytosolic glutathione peroxidase activities. Selenium supplements augmented the cellular immune response through an increased production of interferon gamma and other cytokines, an earlier peak T cell proliferation, and an increase in T helper cells. Humoral immune responses were unaffected. Selenium-supplemented subjects also showed more rapid clearance of the poliovirus, and the poliovirus reverse transcriptase-polymerase chain reaction products recovered from the feces of the supplemented subjects contained a lower number of mutations. CONCLUSIONS The data indicate that these subjects had a functional selenium deficit with suboptimal immune status and a deficit in viral handling. They also suggest that the additional 100 microg Se/d may be insufficient to support optimal function.
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Klapec T, Mandić M, Grgić J, Primorac L, Perl A, Krstanović V. Selenium in selected foods grown or purchased in eastern Croatia. Food Chem 2004. [DOI: 10.1016/j.foodchem.2003.07.031] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Kytö V, Lapatto R, Lakkisto P, Saraste A, Voipio-Pulkki LM, Vuorinen T, Pulkki K. Glutathione depletion and cardiomyocyte apoptosis in viral myocarditis. Eur J Clin Invest 2004; 34:167-75. [PMID: 15025674 DOI: 10.1111/j.1365-2362.2004.01313.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND The course of viral myocarditis is highly variable. Oxidative stress and Bcl-2 family genes may play a role in its pathogenesis by regulating the amount of cardiomyocyte apoptosis. Apoptosis is difficult to detect and quantify in vivo. Therefore, we set to look for indicators of this potentially preventable form of cell death during various phases of experimental murine coxsackievirus B3 myocarditis. METHODS BALB/c mice were infected with the cardiotropic coxsackievirus B3 variant. Glutathione (HPLC), cardiomyocyte apoptosis (TUNEL and caspase-3 cleavage), Bax and Bcl-X(L) mRNA expression (real time RT-PCR), histopathology and viral replication (plaque assay and real time RT-PCR) were measured from day 3 to day 20 after infection. RESULTS Infection caused severe myocarditis and led to progressive decrease of plasma glutathione levels. Myocardial mRNA levels of pro-apoptotic Bax and antiapoptotic Bcl-X(L) were significantly increased from day 3 onwards. Bax mRNA and ratio of Bax to Bcl-X(L) correlated with cardiomyocyte apoptosis (r = 0.77, P = < 0.001 and r 0.51, P < 0.01, respectively). Cardiomyocyte apoptosis was highest on day 5, coinciding with a rapid decline in plasma glutathione (r = -0.52, P = 0.003). CONCLUSIONS Systemic oxidative stress as indicated by decreased plasma glutathione levels coincides with cardiomyocyte apoptosis in experimental coxsackievirus myocarditis. Decreased plasma glutathione levels and changes in cardiac Bax and Bcl-X(L) mRNA expression identify a phase of myocarditis in which the potentially preventable cardiomyocyte apoptosis is mostly observed.
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Affiliation(s)
- V Kytö
- University of Turku, Turku, Finland.
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Abstract
The biochemistry of selenium-containing natural products, including selenoproteins, is reviewed up to May 2002. Particular emphasis is placed on the assimilation of selenium from inorganic and organic selenium sources for selenoprotein synthesis, the catalytic role of selenium in enzymes, and medical implications of an unbalanced selenium supply. The review contains 393 references on key discoveries and recent progress.
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Affiliation(s)
- Marc Birringer
- Dept. of Vitamins and Atherosclerosis, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, D-14558 Bergholz-Rehbrücke, Germany
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Lukevics E, Arsenyan P, Shestakova I, Domracheva I, Kanepe I, Belyakov S, Popelis J, Pudova O. Synthesis, structure and cytotoxicity of organoammonium selenites. Appl Organomet Chem 2002. [DOI: 10.1002/aoc.276] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Sher L. Role of thyroid hormones in the effects of selenium on mood, behavior, and cognitive function. Med Hypotheses 2001; 57:480-3. [PMID: 11601874 DOI: 10.1054/mehy.2001.1369] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Changes in thyroid function may affect mood, behavior, and cognitive function. Selenium is required for appropriate thyroid hormone synthesis, activation, and metabolism. Selenium status influences thyroid function. Selenium status also affects psychological condition and cognitive function. The author suggests that the effects of selenium status on mood, behavior, and cognition may be partly mediated by changes induced by selenium deficiency or selenium supplementation in thyroid function. Selenium deficiency decreases immunocompetence and promotes viral infections. The author proposes that patients who have a combination of depression, hypothyroidism, and increased susceptibility to viral infections, could reasonably be assessed for selenium deficiency, especially if they live in an area where the soil is low in selenium.
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Richard MJ, Guiraud P, Didier C, Seve M, Flores SC, Favier A. Human Immunodeficiency Virus Type 1 Tat Protein Impairs Selenoglutathione Peroxidase Expression and Activity by a Mechanism Independent of Cellular Selenium Uptake: Consequences on Cellular Resistance to UV-A Radiation. Arch Biochem Biophys 2001; 386:213-20. [PMID: 11368344 DOI: 10.1006/abbi.2000.2197] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The expression of the HIV-1 Tat protein in HeLa cells resulted in a 2.5-fold decrease in the activity of the antioxidant enzyme glutathione peroxidase (GPX). This decrease seemed not to be due to a disturbance in selenium (Se) uptake. Indeed, the intracellular level of Se was similar in parental and tat-transfected cells. A Se enrichment of the medium did not lead to an identical GPX activity in both cell lines, suggesting a disturbance in Se utilization. Total intracellular 75Se selenoproteins were analyzed. Several quantitative differences were observed between parental and tat-transfected cells. Mainly, cytoplasmic glutathione peroxidase and a 15-kDa selenoprotein were decreased in HeLa-tat cells, while phospholipid hydroperoxide glutathione peroxidase and low-molecular-mass selenocompounds were increased. Thioredoxin reductase activity and total levels of 75Se-labeled proteins were not different between the two cell types. The effect of Tat on GPX mRNA levels was also analyzed. Northern blots revealed a threefold decrease in the GPX/glyceraldehyde phosphate dehydrogenase mRNA ratio in HeLa-tat versus wild type cells. By deregulating the intracellular oxidant/antioxidant balance, the Tat protein amplified UV sensitivity. The LD50 for ultraviolet radiation A was 90 J/cm2 for HeLa cells and only 65 J/cm2 for HeLa-tat cells. The oxidative stress occurring in the Tat-expressing cells and demonstrated by the diminished ratio of reduced glutathione/oxidized glutathione was not correlated with the intracellular metal content. Cellular iron and copper levels were significantly decreased in HeLa-tat cells. All these disturbances, as well as the previously described decrease in Mn superoxide dismutase activity, are part of the viral strategy to modify the redox potential of cells and may have important consequences for patients.
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Affiliation(s)
- M J Richard
- LBSO/LCR7 No. 8, Université Joseph Fourier, Grenoble, France.
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Taylor EW, Cox AG, Zhao L, Ruzicka JA, Bhat AA, Zhang W, Nadimpalli RG, Dean RG. Nutrition, HIV, and drug abuse: the molecular basis of a unique role for selenium. J Acquir Immune Defic Syndr 2000; 25 Suppl 1:S53-61. [PMID: 11126428 DOI: 10.1097/00042560-200010001-00009] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
HIV-infected injection drug users (IDUs) often suffer from serious nutritional deficiencies. This is a concern because plasma levels of micronutrients such as vitamin B12, zinc, and selenium have been correlated with mortality risk in HIV-positive populations. Injection drug use also increases lipid peroxidation and other indicators of oxidative stress, which, combined with antioxidant deficiencies, can stimulate HIV-1 replication through activation of NF-kappaB transcription factors, while weakening immune defenses. As detailed herein, these prooxidant stimuli can also increase the pathogenic effects of HIV-1 by another mechanism, involving viral selenoproteins. Overlapping the envelope coding region, HIV-1 encodes a truncated glutathione peroxidase (GPx) gene (see #6 in reference list). Sequence analysis and molecular modeling show that this viral GPx (vGPx) module has highly significant structural similarity to known mammalian GPx, with conservation of the catalytic triad of selenocysteine (Sec), glutamine, and tryptophan. In addition to other functions, HIV-1 vGPx may serve as a negative regulator of proviral transcription, by acting as an NF-kappaB inhibitor (a known property of cellular GPx). Another potential selenoprotein coding function of HIV-1 is associated with the 3' end of the nef gene, which terminates in a conserved UGA (potential Sec) codon in the context of a sequence (Cys-Sec) identical to the C-terminal redox center of thioredoxin reductase, another cellular regulator of NF-kappaB. Thus, in combination with known cellular mechanisms involving Se, viral selenoproteins may represent a unique mechanism by which HIV-1 monitors and exploits an essential micronutrient to optimize its replication relative to the host.
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Affiliation(s)
- E W Taylor
- Department of Pharmaceutical and Biomedical Sciences and Computational Center for Molecular Structure and Design, The University of Georgia, Athens 30602, USA.
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Abstract
Nutritional deficiencies are widespread among HIV-1-seropositive male and female drug abusers (injecting drug users, or IDUs), among men who have sex with men (MSM), and among children, although the prevalence of nutritional alterations varies among the groups. Low levels of vitamin A, vitamin B12, zinc, and selenium are common and have been demonstrated to be associated with disease progression and HIV-1 related mortality, independent of CD4 count <200 cells/mm3 at baseline and CD4 count over time. When all nutrient factors that are associated with survival are considered together, only selenium deficiency is a significant predictor of mortality. The profound effect of selenium on disease progression may reflect selenium's action in antioxidant defense systems, as well as gene regulation.
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Affiliation(s)
- M K Baum
- Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Florida 33136, USA
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Baum MK, Miguez-Burbano MJ, Campa A, Shor-Posner G. Selenium and interleukins in persons infected with human immunodeficiency virus type 1. J Infect Dis 2000; 182 Suppl 1:S69-73. [PMID: 10944486 DOI: 10.1086/315911] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
An important role for selenium in human immunodeficiency virus (HIV) disease has been proposed. Decreased selenium levels, as found in persons with HIV infection or AIDS, are sensitive markers of disease progression. Selenium deficiency, an independent predictor of mortality in both HIV-1-infected adults and children, is an essential micronutrient that is associated with an improvement of T cell function and reduced apoptosis in animal models. In addition, adequate selenium may enhance resistance to infections through modulation of interleukin (IL) production and subsequently the Th1/Th2 response. Selenium supplementation up-regulates IL-2 and increases activation, proliferation, differentiation, and programmed cell death of T helper cells. Moreover, selenium supplementation may down-regulate the abnormally high levels of IL-8 and tumor necrosis factor-alpha observed in HIV disease, which has been associated with neurologic damage, Kaposi's sarcoma, wasting syndrome, and increased viral replication. Together, these findings suggest a new mechanism through which selenium may affect HIV-1 disease progression.
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Affiliation(s)
- M K Baum
- Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami, FL 33136, USA.
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Abstract
The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.
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Affiliation(s)
- M P Rayman
- Centre for Nutrition and Food Safety, School of Biological Sciences, University of Surrey, Guildford, UK
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Zhao L, Cox AG, Ruzicka JA, Bhat AA, Zhang W, Taylor EW. Molecular modeling and in vitro activity of an HIV-1-encoded glutathione peroxidase. Proc Natl Acad Sci U S A 2000; 97:6356-61. [PMID: 10841544 PMCID: PMC18607 DOI: 10.1073/pnas.97.12.6356] [Citation(s) in RCA: 70] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Based on theoretical evidence, it has been proposed that HIV-1 may encode several selenoprotein modules, one of which (overlapping the env gp41-coding region) has highly significant sequence similarity to the mammalian selenoprotein glutathione peroxidase (GPx; EC ). The similarity score of the putative HIV-1 viral GPx homolog relative to an aligned set of known GPx is 6.3 SD higher than expected for random sequences of similar composition. Based on that alignment, a molecular model of the HIV-1 GPx was constructed by homology modeling from the bovine GPx crystal structure. Despite extensive truncation relative to the cellular GPx gene, the structural core and the geometry of the catalytic triad of selenocysteine, glutamine, and tryptophan are well conserved in the viral GPx. All of the insertions and deletions predicted by the alignment proved to be structurally feasible. The model is energetically favorable, with a computed molecular mechanics strain energy close to that of the bovine GPx structure, when normalized on a per-residue basis. However, considering the remote homology, this model is intended only to provide a working hypothesis allowing for a similar active site and structural core. To validate the theoretical predictions, we cloned the hypothetical HIV-1 gene and found it to encode functional GPx activity when expressed as a selenoprotein in mammalian cells. In transfected canine kidney cells, the increase in GPx activity ranged from 21% to 43% relative to controls (average 30%, n = 9, P < 0.0001), whereas, in transfected MCF7 cells, which have low endogenous GPx activity, a near 100% increase was observed (average 99%, n = 3, P < 0.05).
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Affiliation(s)
- L Zhao
- Computational Center for Molecular Structure and Design, and Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA
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Berg M, Chasse G, Deretey E, Füzéry A, Fung B, Fung D, Henry-Riyad H, Lin A, Mak M, Mantas A, Patel M, Repyakh I, Staikova M, Salpietro S, Tang TH, Vank J, Perczel A, Csonka G, Farkas Ö, Torday L, Székely Z, Csizmadia I. Prospects in computational molecular medicine: a millennial mega-project on peptide folding. ACTA ACUST UNITED AC 2000. [DOI: 10.1016/s0166-1280(00)00448-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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