VOSalophen: a vanadium complex with a stilbene derivative—induction of apoptosis, autophagy, and efficiency in experimental cutaneous leishmaniasis
In our previous work, we demonstrated the promising in vitro effect of VOSalophen, a vanadium complex with a stilbene derivative, against Leishmania amazonensis . Its antileishmanial activity has been associated with oxidative stress in L. amazonensis promastigotes and L. amazonensis -infected macro...
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Veröffentlicht in: | Journal of biological inorganic chemistry 2017-08, Vol.22 (6), p.929-939 |
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creator | Machado, Patrícia de A. Morais, Jessica O. F. Carvalho, Gustavo S. G. Lima, Wallace P. Macedo, Gilson C. Britta, Elizandra A. Nakamura, Celso V. da Silva, Adilson D. Cuin, Alexandre Coimbra, Elaine S. |
description | In our previous work, we demonstrated the promising in vitro effect of VOSalophen, a vanadium complex with a stilbene derivative, against
Leishmania amazonensis
. Its antileishmanial activity has been associated with oxidative stress in
L. amazonensis
promastigotes and
L. amazonensis
-infected macrophages. In the present study, the mechanism involved in the death of parasites after treatment with VOSalophen, as well as in vivo effect in the murine model cutaneous leishmaniasis, has been investigated. Promastigotes of
L. amazonensis
treated with VOSalophen presented apoptotic cells features, such as cell volume decrease, phosphatidylserine externalization, and DNA fragmentation. An increase in autophagic vacuoles formation in treated promastigotes was also observed, showing that autophagy also may be involved in the death of these parasites. In intracellular amastigotes, DNA fragmentation was observed after treatment with VOSalophen, but this effect was not observed in host cells, highlighting the selective effect of this vanadium complex. In addition, VOSalophen showed activity in the murine model of cutaneous leishmaniasis, without hepatic and renal damages. The outcome described here points out that VOSalophen had promising antileishmanial properties and these data also contribute to the understanding of the mechanisms involved in the death of protozoa induced by metal complexes. |
doi_str_mv | 10.1007/s00775-017-1471-2 |
format | Article |
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Leishmania amazonensis
. Its antileishmanial activity has been associated with oxidative stress in
L. amazonensis
promastigotes and
L. amazonensis
-infected macrophages. In the present study, the mechanism involved in the death of parasites after treatment with VOSalophen, as well as in vivo effect in the murine model cutaneous leishmaniasis, has been investigated. Promastigotes of
L. amazonensis
treated with VOSalophen presented apoptotic cells features, such as cell volume decrease, phosphatidylserine externalization, and DNA fragmentation. An increase in autophagic vacuoles formation in treated promastigotes was also observed, showing that autophagy also may be involved in the death of these parasites. In intracellular amastigotes, DNA fragmentation was observed after treatment with VOSalophen, but this effect was not observed in host cells, highlighting the selective effect of this vanadium complex. In addition, VOSalophen showed activity in the murine model of cutaneous leishmaniasis, without hepatic and renal damages. The outcome described here points out that VOSalophen had promising antileishmanial properties and these data also contribute to the understanding of the mechanisms involved in the death of protozoa induced by metal complexes.</description><identifier>ISSN: 0949-8257</identifier><identifier>EISSN: 1432-1327</identifier><identifier>DOI: 10.1007/s00775-017-1471-2</identifier><identifier>PMID: 28597089</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Amastigotes ; Animal models ; Animals ; Apoptosis ; Apoptosis - drug effects ; Autophagy ; Autophagy - drug effects ; Biochemistry ; Biomedical and Life Sciences ; Cell size ; Cutaneous leishmaniasis ; Death ; Disease Models, Animal ; DNA fragmentation ; DNA Fragmentation - drug effects ; Female ; Inorganic chemistry ; Kidneys ; Leishmaniasis, Cutaneous - drug therapy ; Leishmaniasis, Cutaneous - genetics ; Leishmaniasis, Cutaneous - pathology ; Life Sciences ; Macrophages ; Mice ; Mice, Inbred BALB C ; Microbiology ; Organometallic Compounds - chemistry ; Organometallic Compounds - pharmacology ; Organometallic Compounds - therapeutic use ; Original Paper ; Oxidative stress ; Parasites ; Parasitic diseases ; Phagocytosis ; Phosphatidylserine ; Promastigotes ; Protozoa ; Stilbenes - chemistry ; Vacuoles ; Vanadium ; Vanadium - chemistry</subject><ispartof>Journal of biological inorganic chemistry, 2017-08, Vol.22 (6), p.929-939</ispartof><rights>SBIC 2017</rights><rights>Copyright Springer Science & Business Media 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-8cc5f25f1346a742882e3c2d4ec0c167552a01955b366c508e14c7c94e5729573</citedby><cites>FETCH-LOGICAL-c372t-8cc5f25f1346a742882e3c2d4ec0c167552a01955b366c508e14c7c94e5729573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00775-017-1471-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00775-017-1471-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28597089$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Machado, Patrícia de A.</creatorcontrib><creatorcontrib>Morais, Jessica O. F.</creatorcontrib><creatorcontrib>Carvalho, Gustavo S. G.</creatorcontrib><creatorcontrib>Lima, Wallace P.</creatorcontrib><creatorcontrib>Macedo, Gilson C.</creatorcontrib><creatorcontrib>Britta, Elizandra A.</creatorcontrib><creatorcontrib>Nakamura, Celso V.</creatorcontrib><creatorcontrib>da Silva, Adilson D.</creatorcontrib><creatorcontrib>Cuin, Alexandre</creatorcontrib><creatorcontrib>Coimbra, Elaine S.</creatorcontrib><title>VOSalophen: a vanadium complex with a stilbene derivative—induction of apoptosis, autophagy, and efficiency in experimental cutaneous leishmaniasis</title><title>Journal of biological inorganic chemistry</title><addtitle>J Biol Inorg Chem</addtitle><addtitle>J Biol Inorg Chem</addtitle><description>In our previous work, we demonstrated the promising in vitro effect of VOSalophen, a vanadium complex with a stilbene derivative, against
Leishmania amazonensis
. Its antileishmanial activity has been associated with oxidative stress in
L. amazonensis
promastigotes and
L. amazonensis
-infected macrophages. In the present study, the mechanism involved in the death of parasites after treatment with VOSalophen, as well as in vivo effect in the murine model cutaneous leishmaniasis, has been investigated. Promastigotes of
L. amazonensis
treated with VOSalophen presented apoptotic cells features, such as cell volume decrease, phosphatidylserine externalization, and DNA fragmentation. An increase in autophagic vacuoles formation in treated promastigotes was also observed, showing that autophagy also may be involved in the death of these parasites. In intracellular amastigotes, DNA fragmentation was observed after treatment with VOSalophen, but this effect was not observed in host cells, highlighting the selective effect of this vanadium complex. In addition, VOSalophen showed activity in the murine model of cutaneous leishmaniasis, without hepatic and renal damages. The outcome described here points out that VOSalophen had promising antileishmanial properties and these data also contribute to the understanding of the mechanisms involved in the death of protozoa induced by metal complexes.</description><subject>Amastigotes</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cell size</subject><subject>Cutaneous leishmaniasis</subject><subject>Death</subject><subject>Disease Models, Animal</subject><subject>DNA fragmentation</subject><subject>DNA Fragmentation - drug effects</subject><subject>Female</subject><subject>Inorganic chemistry</subject><subject>Kidneys</subject><subject>Leishmaniasis, Cutaneous - drug therapy</subject><subject>Leishmaniasis, Cutaneous - genetics</subject><subject>Leishmaniasis, Cutaneous - pathology</subject><subject>Life Sciences</subject><subject>Macrophages</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbiology</subject><subject>Organometallic Compounds - chemistry</subject><subject>Organometallic Compounds - pharmacology</subject><subject>Organometallic Compounds - therapeutic use</subject><subject>Original Paper</subject><subject>Oxidative stress</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Phagocytosis</subject><subject>Phosphatidylserine</subject><subject>Promastigotes</subject><subject>Protozoa</subject><subject>Stilbenes - chemistry</subject><subject>Vacuoles</subject><subject>Vanadium</subject><subject>Vanadium - chemistry</subject><issn>0949-8257</issn><issn>1432-1327</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctu1DAUhi1ERYfCA7BBltiwIMXXsc2uqrhJlbrgsrU8zknHVWKH2Bk6Ox4CXrBPgkcpqEJi42P5fP58rB-hZ5ScUkLU61wXJRtCVUOFog17gFZUcNZQztRDtCJGmEYzqY7R45yvCSFcUvkIHTMtjSLarNCvr5efXJ_GLcQ32OGdi64N84B9GsYebvD3ULb1PJfQbyACbmEKO1fCDm5__AyxnX0JKeLUYTemsaQc8ivs5lKN7mpft7HF0HXBB4h-j0PEcDNWxwCxuB77ubgIac64h5C3g4vBVcUTdNS5PsPTu3qCvrx7-_n8Q3Nx-f7j-dlF47lipdHey47JjnKxdkowrRlwz1oBnni6VlIyR6iRcsPXay-JBiq88kaAVMxIxU_Qy8U7TunbDLnYIWQPfb8MZakhWnCpBavoi3_Q6zRPsU5XKUa4EVrSStGF8lPKeYLOjvWvbtpbSuwhM7tkZmtm9pCZPZif35nnzQDt3xt_QqoAW4BcW_EKpntP_9f6G4LApF8</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Machado, Patrícia de A.</creator><creator>Morais, Jessica O. F.</creator><creator>Carvalho, Gustavo S. G.</creator><creator>Lima, Wallace P.</creator><creator>Macedo, Gilson C.</creator><creator>Britta, Elizandra A.</creator><creator>Nakamura, Celso V.</creator><creator>da Silva, Adilson D.</creator><creator>Cuin, Alexandre</creator><creator>Coimbra, Elaine S.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20170801</creationdate><title>VOSalophen: a vanadium complex with a stilbene derivative—induction of apoptosis, autophagy, and efficiency in experimental cutaneous leishmaniasis</title><author>Machado, Patrícia de A. ; Morais, Jessica O. F. ; Carvalho, Gustavo S. G. ; Lima, Wallace P. ; Macedo, Gilson C. ; Britta, Elizandra A. ; Nakamura, Celso V. ; da Silva, Adilson D. ; Cuin, Alexandre ; Coimbra, Elaine S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-8cc5f25f1346a742882e3c2d4ec0c167552a01955b366c508e14c7c94e5729573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amastigotes</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Autophagy</topic><topic>Autophagy - drug effects</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cell size</topic><topic>Cutaneous leishmaniasis</topic><topic>Death</topic><topic>Disease Models, Animal</topic><topic>DNA fragmentation</topic><topic>DNA Fragmentation - drug effects</topic><topic>Female</topic><topic>Inorganic chemistry</topic><topic>Kidneys</topic><topic>Leishmaniasis, Cutaneous - drug therapy</topic><topic>Leishmaniasis, Cutaneous - genetics</topic><topic>Leishmaniasis, Cutaneous - pathology</topic><topic>Life Sciences</topic><topic>Macrophages</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbiology</topic><topic>Organometallic Compounds - chemistry</topic><topic>Organometallic Compounds - pharmacology</topic><topic>Organometallic Compounds - therapeutic use</topic><topic>Original Paper</topic><topic>Oxidative stress</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Phagocytosis</topic><topic>Phosphatidylserine</topic><topic>Promastigotes</topic><topic>Protozoa</topic><topic>Stilbenes - chemistry</topic><topic>Vacuoles</topic><topic>Vanadium</topic><topic>Vanadium - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Machado, Patrícia de A.</creatorcontrib><creatorcontrib>Morais, Jessica O. F.</creatorcontrib><creatorcontrib>Carvalho, Gustavo S. G.</creatorcontrib><creatorcontrib>Lima, Wallace P.</creatorcontrib><creatorcontrib>Macedo, Gilson C.</creatorcontrib><creatorcontrib>Britta, Elizandra A.</creatorcontrib><creatorcontrib>Nakamura, Celso V.</creatorcontrib><creatorcontrib>da Silva, Adilson D.</creatorcontrib><creatorcontrib>Cuin, Alexandre</creatorcontrib><creatorcontrib>Coimbra, Elaine S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biological inorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Machado, Patrícia de A.</au><au>Morais, Jessica O. F.</au><au>Carvalho, Gustavo S. G.</au><au>Lima, Wallace P.</au><au>Macedo, Gilson C.</au><au>Britta, Elizandra A.</au><au>Nakamura, Celso V.</au><au>da Silva, Adilson D.</au><au>Cuin, Alexandre</au><au>Coimbra, Elaine S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>VOSalophen: a vanadium complex with a stilbene derivative—induction of apoptosis, autophagy, and efficiency in experimental cutaneous leishmaniasis</atitle><jtitle>Journal of biological inorganic chemistry</jtitle><stitle>J Biol Inorg Chem</stitle><addtitle>J Biol Inorg Chem</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>22</volume><issue>6</issue><spage>929</spage><epage>939</epage><pages>929-939</pages><issn>0949-8257</issn><eissn>1432-1327</eissn><abstract>In our previous work, we demonstrated the promising in vitro effect of VOSalophen, a vanadium complex with a stilbene derivative, against
Leishmania amazonensis
. Its antileishmanial activity has been associated with oxidative stress in
L. amazonensis
promastigotes and
L. amazonensis
-infected macrophages. In the present study, the mechanism involved in the death of parasites after treatment with VOSalophen, as well as in vivo effect in the murine model cutaneous leishmaniasis, has been investigated. Promastigotes of
L. amazonensis
treated with VOSalophen presented apoptotic cells features, such as cell volume decrease, phosphatidylserine externalization, and DNA fragmentation. An increase in autophagic vacuoles formation in treated promastigotes was also observed, showing that autophagy also may be involved in the death of these parasites. In intracellular amastigotes, DNA fragmentation was observed after treatment with VOSalophen, but this effect was not observed in host cells, highlighting the selective effect of this vanadium complex. In addition, VOSalophen showed activity in the murine model of cutaneous leishmaniasis, without hepatic and renal damages. The outcome described here points out that VOSalophen had promising antileishmanial properties and these data also contribute to the understanding of the mechanisms involved in the death of protozoa induced by metal complexes.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>28597089</pmid><doi>10.1007/s00775-017-1471-2</doi><tpages>11</tpages></addata></record> |
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subjects | Amastigotes Animal models Animals Apoptosis Apoptosis - drug effects Autophagy Autophagy - drug effects Biochemistry Biomedical and Life Sciences Cell size Cutaneous leishmaniasis Death Disease Models, Animal DNA fragmentation DNA Fragmentation - drug effects Female Inorganic chemistry Kidneys Leishmaniasis, Cutaneous - drug therapy Leishmaniasis, Cutaneous - genetics Leishmaniasis, Cutaneous - pathology Life Sciences Macrophages Mice Mice, Inbred BALB C Microbiology Organometallic Compounds - chemistry Organometallic Compounds - pharmacology Organometallic Compounds - therapeutic use Original Paper Oxidative stress Parasites Parasitic diseases Phagocytosis Phosphatidylserine Promastigotes Protozoa Stilbenes - chemistry Vacuoles Vanadium Vanadium - chemistry |
title | VOSalophen: a vanadium complex with a stilbene derivative—induction of apoptosis, autophagy, and efficiency in experimental cutaneous leishmaniasis |
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