Ultrastructural and morphological changes in Leishmania (Viannia) braziliensis treated with synthetic chalcones
Cutaneous leishmaniasis has an estimated incidence of 1.5 million new cases per year and the treatment options available are old, expensive, toxic, and difficult to administer. Chalcones have shown good activity against several species of Leishmania. However few studies have discussed the mechanisms...
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Veröffentlicht in: | Experimental parasitology 2016-01, Vol.160, p.23-30 |
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creator | de Mello, Tatiane F.P. Cardoso, Bruna M. Bitencourt, Heriberto R. Donatti, Lucélia Aristides, Sandra M.A. Lonardoni, Maria V.C. Silveira, Thais G.V. |
description | Cutaneous leishmaniasis has an estimated incidence of 1.5 million new cases per year and the treatment options available are old, expensive, toxic, and difficult to administer. Chalcones have shown good activity against several species of Leishmania. However few studies have discussed the mechanisms of action and drug target of this group of compounds in Leishmania. The synthetic chalcones that were evaluated in the present study were previously shown to exhibit activity against Leishmania (Viannia) braziliensis. The objective of the present study was to identify ultrastructural and morphological changes in L. (V.) braziliensis after treatment with three synthetic chalcones (1–3). Promastigotes were treated with chalcones 1–3 and evaluated by transmission and scanning electron microscopy. Cellular and nuclear morphology of the parasites, changes in membrane permeability, and DNA fragmentation in agarose electrophoresis gel were also investigated after exposure to synthetic chalcones. All three synthetic chalcones (1–3) induced ultrastructural alterations in mitochondria, intense vacuolization, two nuclei with rounding of parasites, and cellular and nuclear shrinkage. Chalcones 1–3 also induced no changes in membrane permeability, and presence of nucleosome-sized DNA fragments. Synthetic chalcones 1–3 induced ultrastructural and morphological changes, suggesting that chalcones 1–3 induce apoptosis-like cell death. Further studies should be conducted to elucidate other aspects of the action of these chalcones against Leishmania spp. and their use for the treatment of cutaneous leishmaniasis.
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•Chalcones 1–3 induced mitochondrial changes in promastigotes of L. (V.) braziliensis.•Synthetic chalcones 1–3 induced rounded shape in L. (V.) braziliensis.•Chalcones 1–3 showed cytoplasmic and nuclear shrinkage in L. (V.) braziliensis.•Chalcones 1–3 exhibited nucleosome-sized DNA fragments in L. (V.) braziliensis.•Chalcones induced changes in promastigotes suggesting apoptosis-like cell death. |
doi_str_mv | 10.1016/j.exppara.2015.11.005 |
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[Display omitted]
•Chalcones 1–3 induced mitochondrial changes in promastigotes of L. (V.) braziliensis.•Synthetic chalcones 1–3 induced rounded shape in L. (V.) braziliensis.•Chalcones 1–3 showed cytoplasmic and nuclear shrinkage in L. (V.) braziliensis.•Chalcones 1–3 exhibited nucleosome-sized DNA fragments in L. (V.) braziliensis.•Chalcones induced changes in promastigotes suggesting apoptosis-like cell death.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1016/j.exppara.2015.11.005</identifier><identifier>PMID: 26632504</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Apoptosis ; Cell death ; Cell Membrane Permeability - drug effects ; Cell Nucleus - drug effects ; Chalcones ; Chalcones - chemical synthesis ; Chalcones - pharmacology ; Cricetinae ; DNA Fragmentation - drug effects ; In Situ Nick-End Labeling ; Leishmania ; Leishmania braziliensis ; Leishmania braziliensis - drug effects ; Leishmania braziliensis - ultrastructure ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mitochondria - drug effects ; Promastigotes ; Ultrastructure ; Vacuoles - drug effects ; Viannia braziliensis</subject><ispartof>Experimental parasitology, 2016-01, Vol.160, p.23-30</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-b8d7bf53e222820052bf08238ba8883f6f5f32a63909b237f9553d71dc44a5f03</citedby><cites>FETCH-LOGICAL-c398t-b8d7bf53e222820052bf08238ba8883f6f5f32a63909b237f9553d71dc44a5f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014489415300631$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26632504$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Mello, Tatiane F.P.</creatorcontrib><creatorcontrib>Cardoso, Bruna M.</creatorcontrib><creatorcontrib>Bitencourt, Heriberto R.</creatorcontrib><creatorcontrib>Donatti, Lucélia</creatorcontrib><creatorcontrib>Aristides, Sandra M.A.</creatorcontrib><creatorcontrib>Lonardoni, Maria V.C.</creatorcontrib><creatorcontrib>Silveira, Thais G.V.</creatorcontrib><title>Ultrastructural and morphological changes in Leishmania (Viannia) braziliensis treated with synthetic chalcones</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>Cutaneous leishmaniasis has an estimated incidence of 1.5 million new cases per year and the treatment options available are old, expensive, toxic, and difficult to administer. Chalcones have shown good activity against several species of Leishmania. However few studies have discussed the mechanisms of action and drug target of this group of compounds in Leishmania. The synthetic chalcones that were evaluated in the present study were previously shown to exhibit activity against Leishmania (Viannia) braziliensis. The objective of the present study was to identify ultrastructural and morphological changes in L. (V.) braziliensis after treatment with three synthetic chalcones (1–3). Promastigotes were treated with chalcones 1–3 and evaluated by transmission and scanning electron microscopy. Cellular and nuclear morphology of the parasites, changes in membrane permeability, and DNA fragmentation in agarose electrophoresis gel were also investigated after exposure to synthetic chalcones. All three synthetic chalcones (1–3) induced ultrastructural alterations in mitochondria, intense vacuolization, two nuclei with rounding of parasites, and cellular and nuclear shrinkage. Chalcones 1–3 also induced no changes in membrane permeability, and presence of nucleosome-sized DNA fragments. Synthetic chalcones 1–3 induced ultrastructural and morphological changes, suggesting that chalcones 1–3 induce apoptosis-like cell death. Further studies should be conducted to elucidate other aspects of the action of these chalcones against Leishmania spp. and their use for the treatment of cutaneous leishmaniasis.
[Display omitted]
•Chalcones 1–3 induced mitochondrial changes in promastigotes of L. (V.) braziliensis.•Synthetic chalcones 1–3 induced rounded shape in L. (V.) braziliensis.•Chalcones 1–3 showed cytoplasmic and nuclear shrinkage in L. (V.) braziliensis.•Chalcones 1–3 exhibited nucleosome-sized DNA fragments in L. (V.) braziliensis.•Chalcones induced changes in promastigotes suggesting apoptosis-like cell death.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Cell death</subject><subject>Cell Membrane Permeability - drug effects</subject><subject>Cell Nucleus - drug effects</subject><subject>Chalcones</subject><subject>Chalcones - chemical synthesis</subject><subject>Chalcones - pharmacology</subject><subject>Cricetinae</subject><subject>DNA Fragmentation - drug effects</subject><subject>In Situ Nick-End Labeling</subject><subject>Leishmania</subject><subject>Leishmania braziliensis</subject><subject>Leishmania braziliensis - drug effects</subject><subject>Leishmania braziliensis - ultrastructure</subject><subject>Microscopy, Electron, Scanning</subject><subject>Microscopy, Electron, Transmission</subject><subject>Mitochondria - drug effects</subject><subject>Promastigotes</subject><subject>Ultrastructure</subject><subject>Vacuoles - drug effects</subject><subject>Viannia braziliensis</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EotvCTwDlWA4J46_EOSFUQUFaiQvlajnOuPEqiYPtFMqvJ6tduMJpRqNnvt6XkFcUKgq0fnuo8OeymGgqBlRWlFYA8gnZUWihZEK0T8kOgIpSqFZckMuUDgCgKBPPyQWra84kiB0Jd2OOJuW42rxGMxZm7ospxGUIY7j3dqvYwcz3mAo_F3v0aZjM7E1x_c2beUveFF00v_zocU4-FTmiydgXP3weivQ45wGzt8cZow0zphfkmTNjwpfneEXuPn74evOp3H-5_Xzzfl9a3qpcdqpvOic5MsYU2z5jnQPFuOqMUoq72knHmal5C23HeONaKXnf0N4KYaQDfkWuT3OXGL6vmLKefLI4jmbGsCZNm5px2Yqm-R8UVC1bKTZUnlAbQ0oRnV6in0x81BT00RZ90Gdb9NEWTanejt_6Xp9XrN2E_d-uPz5swLsTgJsmDx6jTnZT1GLvI9qs--D_seI3-nCiEA</recordid><startdate>201601</startdate><enddate>201601</enddate><creator>de Mello, Tatiane F.P.</creator><creator>Cardoso, Bruna M.</creator><creator>Bitencourt, Heriberto R.</creator><creator>Donatti, Lucélia</creator><creator>Aristides, Sandra M.A.</creator><creator>Lonardoni, Maria V.C.</creator><creator>Silveira, Thais G.V.</creator><general>Elsevier Inc</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><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>M7N</scope></search><sort><creationdate>201601</creationdate><title>Ultrastructural and morphological changes in Leishmania (Viannia) braziliensis treated with synthetic chalcones</title><author>de Mello, Tatiane F.P. ; 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Chalcones have shown good activity against several species of Leishmania. However few studies have discussed the mechanisms of action and drug target of this group of compounds in Leishmania. The synthetic chalcones that were evaluated in the present study were previously shown to exhibit activity against Leishmania (Viannia) braziliensis. The objective of the present study was to identify ultrastructural and morphological changes in L. (V.) braziliensis after treatment with three synthetic chalcones (1–3). Promastigotes were treated with chalcones 1–3 and evaluated by transmission and scanning electron microscopy. Cellular and nuclear morphology of the parasites, changes in membrane permeability, and DNA fragmentation in agarose electrophoresis gel were also investigated after exposure to synthetic chalcones. All three synthetic chalcones (1–3) induced ultrastructural alterations in mitochondria, intense vacuolization, two nuclei with rounding of parasites, and cellular and nuclear shrinkage. Chalcones 1–3 also induced no changes in membrane permeability, and presence of nucleosome-sized DNA fragments. Synthetic chalcones 1–3 induced ultrastructural and morphological changes, suggesting that chalcones 1–3 induce apoptosis-like cell death. Further studies should be conducted to elucidate other aspects of the action of these chalcones against Leishmania spp. and their use for the treatment of cutaneous leishmaniasis.
[Display omitted]
•Chalcones 1–3 induced mitochondrial changes in promastigotes of L. (V.) braziliensis.•Synthetic chalcones 1–3 induced rounded shape in L. (V.) braziliensis.•Chalcones 1–3 showed cytoplasmic and nuclear shrinkage in L. (V.) braziliensis.•Chalcones 1–3 exhibited nucleosome-sized DNA fragments in L. (V.) braziliensis.•Chalcones induced changes in promastigotes suggesting apoptosis-like cell death.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26632504</pmid><doi>10.1016/j.exppara.2015.11.005</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Apoptosis Cell death Cell Membrane Permeability - drug effects Cell Nucleus - drug effects Chalcones Chalcones - chemical synthesis Chalcones - pharmacology Cricetinae DNA Fragmentation - drug effects In Situ Nick-End Labeling Leishmania Leishmania braziliensis Leishmania braziliensis - drug effects Leishmania braziliensis - ultrastructure Microscopy, Electron, Scanning Microscopy, Electron, Transmission Mitochondria - drug effects Promastigotes Ultrastructure Vacuoles - drug effects Viannia braziliensis |
title | Ultrastructural and morphological changes in Leishmania (Viannia) braziliensis treated with synthetic chalcones |
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