Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load
Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increa...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2021-03, Vol.15 (3), p.e0009214-e0009214 |
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| creator | da Silva, Pedro Henrique Lopes de Castro, Katherine Kelda Gomes Mendes, Mayara Abud Calvo, Thyago Leal Leal, Júlia Monteiro Pereira Hacker, Mariana de Andréa Vilas-Boas Nery, José Augusto da Costa Sarno, Euzenir Nunes Lourenço, Roberto Alves Moraes, Milton Ozório Lara, Flávio Alves Esquenazi, Danuza |
| description | Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy.
87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase.
We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease. |
| doi_str_mv | 10.1371/journal.pntd.0009214 |
| format | Article |
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87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase.
We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0009214</identifier><identifier>PMID: 33690671</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accumulation ; Age ; Aged patients ; Ageing ; Aging ; Binding sites ; Biology and Life Sciences ; Biomolecules ; Biopsy ; Carbonyls ; Damage accumulation ; Demographic aspects ; Developing countries ; Development and progression ; Enzymes ; Free radicals ; Gene expression ; Geriatrics ; Health aspects ; Health care ; Immune system ; Infectious diseases ; Laboratories ; LDCs ; Leprosy ; Malondialdehyde ; Medicine and Health Sciences ; Mitochondria ; Molecules ; Older people ; Oxidation ; Oxidative stress ; Physiological aspects ; Population ; Proteins ; Reactive oxygen species ; Target recognition ; Tropical diseases</subject><ispartof>PLoS neglected tropical diseases, 2021-03, Vol.15 (3), p.e0009214-e0009214</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 da Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 da Silva et al 2021 da Silva et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-13abf858ccdd39029eb8ebb36be4f8b4cb00cda49509a40e4bf358e2d29439633</citedby><cites>FETCH-LOGICAL-c624t-13abf858ccdd39029eb8ebb36be4f8b4cb00cda49509a40e4bf358e2d29439633</cites><orcidid>0000-0002-1312-7161 ; 0000-0002-3373-8963 ; 0000-0003-0418-8760 ; 0000-0003-0838-1285</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978340/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978340/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33690671$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>da Silva, Pedro Henrique Lopes</creatorcontrib><creatorcontrib>de Castro, Katherine Kelda Gomes</creatorcontrib><creatorcontrib>Mendes, Mayara Abud</creatorcontrib><creatorcontrib>Calvo, Thyago Leal</creatorcontrib><creatorcontrib>Leal, Júlia Monteiro Pereira</creatorcontrib><creatorcontrib>Hacker, Mariana de Andréa Vilas-Boas</creatorcontrib><creatorcontrib>Nery, José Augusto da Costa</creatorcontrib><creatorcontrib>Sarno, Euzenir Nunes</creatorcontrib><creatorcontrib>Lourenço, Roberto Alves</creatorcontrib><creatorcontrib>Moraes, Milton Ozório</creatorcontrib><creatorcontrib>Lara, Flávio Alves</creatorcontrib><creatorcontrib>Esquenazi, Danuza</creatorcontrib><title>Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy.
87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase.
We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.</description><subject>Accumulation</subject><subject>Age</subject><subject>Aged patients</subject><subject>Ageing</subject><subject>Aging</subject><subject>Binding sites</subject><subject>Biology and Life Sciences</subject><subject>Biomolecules</subject><subject>Biopsy</subject><subject>Carbonyls</subject><subject>Damage accumulation</subject><subject>Demographic aspects</subject><subject>Developing countries</subject><subject>Development and progression</subject><subject>Enzymes</subject><subject>Free radicals</subject><subject>Gene expression</subject><subject>Geriatrics</subject><subject>Health aspects</subject><subject>Health care</subject><subject>Immune system</subject><subject>Infectious diseases</subject><subject>Laboratories</subject><subject>LDCs</subject><subject>Leprosy</subject><subject>Malondialdehyde</subject><subject>Medicine and Health Sciences</subject><subject>Mitochondria</subject><subject>Molecules</subject><subject>Older people</subject><subject>Oxidation</subject><subject>Oxidative stress</subject><subject>Physiological aspects</subject><subject>Population</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Target recognition</subject><subject>Tropical 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oxidative stress in elderly leprosy patients is related to age but not to bacillary load</title><author>da Silva, Pedro Henrique Lopes ; de Castro, Katherine Kelda Gomes ; Mendes, Mayara Abud ; Calvo, Thyago Leal ; Leal, Júlia Monteiro Pereira ; Hacker, Mariana de Andréa Vilas-Boas ; Nery, José Augusto da Costa ; Sarno, Euzenir Nunes ; Lourenço, Roberto Alves ; Moraes, Milton Ozório ; Lara, Flávio Alves ; Esquenazi, Danuza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-13abf858ccdd39029eb8ebb36be4f8b4cb00cda49509a40e4bf358e2d29439633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Accumulation</topic><topic>Age</topic><topic>Aged patients</topic><topic>Ageing</topic><topic>Aging</topic><topic>Binding sites</topic><topic>Biology and Life Sciences</topic><topic>Biomolecules</topic><topic>Biopsy</topic><topic>Carbonyls</topic><topic>Damage 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Danuza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>15</volume><issue>3</issue><spage>e0009214</spage><epage>e0009214</epage><pages>e0009214-e0009214</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy.
87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase.
We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33690671</pmid><doi>10.1371/journal.pntd.0009214</doi><orcidid>https://orcid.org/0000-0002-1312-7161</orcidid><orcidid>https://orcid.org/0000-0002-3373-8963</orcidid><orcidid>https://orcid.org/0000-0003-0418-8760</orcidid><orcidid>https://orcid.org/0000-0003-0838-1285</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2021-03, Vol.15 (3), p.e0009214-e0009214 |
| issn | 1935-2735 1935-2727 1935-2735 |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Accumulation Age Aged patients Ageing Aging Binding sites Biology and Life Sciences Biomolecules Biopsy Carbonyls Damage accumulation Demographic aspects Developing countries Development and progression Enzymes Free radicals Gene expression Geriatrics Health aspects Health care Immune system Infectious diseases Laboratories LDCs Leprosy Malondialdehyde Medicine and Health Sciences Mitochondria Molecules Older people Oxidation Oxidative stress Physiological aspects Population Proteins Reactive oxygen species Target recognition Tropical diseases |
| title | Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T08%3A50%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Increased%20oxidative%20stress%20in%20elderly%20leprosy%20patients%20is%20related%20to%20age%20but%20not%20to%20bacillary%20load&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=da%20Silva,%20Pedro%20Henrique%20Lopes&rft.date=2021-03-01&rft.volume=15&rft.issue=3&rft.spage=e0009214&rft.epage=e0009214&rft.pages=e0009214-e0009214&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0009214&rft_dat=%3Cgale_plos_%3EA658711638%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2513691715&rft_id=info:pmid/33690671&rft_galeid=A658711638&rft_doaj_id=oai_doaj_org_article_a181ef0308d54d73b544ba0751da2c92&rfr_iscdi=true |