Oxidative stress plays major role in mediating apoptosis in filarial nematode Setaria cervi in the presence of trans-stilbene derivatives.
Identifieur interne : 000D19 ( Main/Exploration ); précédent : 000D18; suivant : 000D20Oxidative stress plays major role in mediating apoptosis in filarial nematode Setaria cervi in the presence of trans-stilbene derivatives.
Auteurs : Niladri Mukherjee [Inde] ; Pravat Kumar Parida [Inde] ; Abhishek Santra [Inde] ; Tamashree Ghosh [Inde] ; Ananya Dutta [Inde] ; Kuladip Jana [Inde] ; Anup Kumar Misra [Inde] ; Santi P. Sinha Babu [Inde]Source :
- Free radical biology & medicine [ 1873-4596 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Apoptose (), Caspases (biosynthèse), Caspases (métabolisme), Espèces réactives de l'oxygène (métabolisme), Filariose lymphatique (métabolisme), Filariose lymphatique (parasitologie), Filariose lymphatique (traitement médicamenteux), Fragmentation de l'ADN (), Humains, Peroxyde d'hydrogène (métabolisme), Régulation de l'expression des gènes (), Setaria (nématode) (), Setaria (nématode) (pathogénicité), Stilbènes (), Stilbènes (pharmacologie), Stilbènes (synthèse chimique), Stress oxydatif ().
- MESH :
- biosynthèse : Caspases.
- métabolisme : Caspases, Espèces réactives de l'oxygène, Filariose lymphatique, Peroxyde d'hydrogène.
- parasitologie : Filariose lymphatique.
- pathogénicité : Setaria (nématode).
- pharmacologie : Stilbènes.
- synthèse chimique : Stilbènes.
- traitement médicamenteux : Filariose lymphatique.
- Animaux, Apoptose, Fragmentation de l'ADN, Humains, Régulation de l'expression des gènes, Setaria (nématode), Stilbènes, Stress oxydatif.
English descriptors
- KwdEn :
- Animals, Apoptosis (drug effects), Caspases (biosynthesis), Caspases (metabolism), DNA Fragmentation (drug effects), Elephantiasis, Filarial (drug therapy), Elephantiasis, Filarial (metabolism), Elephantiasis, Filarial (parasitology), Gene Expression Regulation (drug effects), Humans, Hydrogen Peroxide (metabolism), Oxidative Stress (drug effects), Reactive Oxygen Species (metabolism), Setaria Nematode (drug effects), Setaria Nematode (pathogenicity), Stilbenes (chemical synthesis), Stilbenes (chemistry), Stilbenes (pharmacology).
- MESH :
- chemical , biosynthesis : Caspases.
- chemical , chemical synthesis : Stilbenes.
- chemical , chemistry : Stilbenes.
- drug effects : Apoptosis, DNA Fragmentation, Gene Expression Regulation, Oxidative Stress, Setaria Nematode.
- drug therapy : Elephantiasis, Filarial.
- chemical , metabolism : Caspases, Elephantiasis, Filarial, Hydrogen Peroxide, Reactive Oxygen Species.
- parasitology : Elephantiasis, Filarial.
- pathogenicity : Setaria Nematode.
- chemical , pharmacology : Stilbenes.
- Animals, Humans.
Abstract
Lymphatic filariasis, affecting around 120 million people in 80 countries worldwide, is an extremely painful disease and caused permanent and long term disability. Owing to its alarming prevalence there is immediate need for development of new therapeutics. A series of trans-stilbene derivatives were synthesized using aqueous reaction condition showing potential as antifilarial agents demonstrated in vitro. MTT reduction assay and dye exclusion test were performed to evaluate the micro and macrofilaricidal potential of these compounds. Amid 20 trans-stilbene derivatives together with Resveratrol (RSV), a multifunctional natural product was screened; nine compounds (28, 29, 33, 35, 36, 38, 39, 41 and 42) have showed promising micro and macrofilaricidal activities and four of them (28, 39, 41 and 42) showed better effectiveness than RSV. In the treated parasites apoptosis was established by DNA laddering, in situ DNA fragmentation and FACS analysis. The generation of ROS in the treated parasites was indicated by the depletion in the level of GSH, GR and GST activity and elevation of SOD, catalase, GPx activity and superoxide anion and H2O2 level. Along with the ROS generation and oxidative stress, the decreased expression of anti-apoptotic ced-9 gene and increased expression of nematode specific pro-apoptotic genes, egl-1, ced-4 and ced-3 at the level of transcription and translation level; the up-regulation of caspase-3 activity and involvement of caspase-8,9,3, cytochrome-c and PARP were also observed and which denotes the probable existence of both extrinsic and intrinsic pathways apoptosis in parasitic nematodes. This observation is reported first time and thus it confirmed the mode of action and effectiveness of the compounds. Further, the comparative bioavailability-pharmacokinetics studies showed that compound 28 possesses comparable properties with Ivermectin. This study will certainly intensify our understanding of the pharmacological importance of trans-stilbenes as an anti-filarial agent.
DOI: 10.1016/j.freeradbiomed.2016.01.027
PubMed: 26849945
Affiliations:
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Scheme VII M, Kolkata 700054, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054</wicri:regionArea><wicri:noRegion>Kolkata 700054</wicri:noRegion></affiliation></author><author><name sortKey="Santra, Abhishek" sort="Santra, Abhishek" uniqKey="Santra A" first="Abhishek" last="Santra">Abhishek Santra</name><affiliation wicri:level="1"><nlm:affiliation>Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. 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Scheme VII M, Kolkata 700054, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054</wicri:regionArea><wicri:noRegion>Kolkata 700054</wicri:noRegion></affiliation></author><author><name sortKey="Jana, Kuladip" sort="Jana, Kuladip" uniqKey="Jana K" first="Kuladip" last="Jana">Kuladip Jana</name><affiliation wicri:level="1"><nlm:affiliation>Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India. Electronic address: kuladip.jana@gmail.com.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054</wicri:regionArea><wicri:noRegion>Kolkata 700054</wicri:noRegion></affiliation></author><author><name sortKey="Misra, Anup Kumar" sort="Misra, Anup Kumar" uniqKey="Misra A" first="Anup Kumar" last="Misra">Anup Kumar Misra</name><affiliation wicri:level="1"><nlm:affiliation>Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India. Electronic address: akmisra69@gmail.com.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054</wicri:regionArea><wicri:noRegion>Kolkata 700054</wicri:noRegion></affiliation></author><author><name sortKey="Sinha Babu, Santi P" sort="Sinha Babu, Santi P" uniqKey="Sinha Babu S" first="Santi P" last="Sinha Babu">Santi P. Sinha Babu</name><affiliation wicri:level="1"><nlm:affiliation>Parasitology Laboratory, Department of Zoology (Centre for Advanced Studies), Visva-Bharati University, Santiniketan 731 235, West Bengal, India. Electronic address: spsinhababu@gmail.com.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Parasitology Laboratory, Department of Zoology (Centre for Advanced Studies), Visva-Bharati University, Santiniketan 731 235, West Bengal</wicri:regionArea><wicri:noRegion>West Bengal</wicri:noRegion></affiliation></author></analytic><series><title level="j">Free radical biology & medicine</title><idno type="eISSN">1873-4596</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Apoptosis (drug effects)</term><term>Caspases (biosynthesis)</term><term>Caspases (metabolism)</term><term>DNA Fragmentation (drug effects)</term><term>Elephantiasis, Filarial (drug therapy)</term><term>Elephantiasis, Filarial (metabolism)</term><term>Elephantiasis, Filarial (parasitology)</term><term>Gene Expression Regulation (drug effects)</term><term>Humans</term><term>Hydrogen Peroxide (metabolism)</term><term>Oxidative Stress (drug effects)</term><term>Reactive Oxygen Species (metabolism)</term><term>Setaria Nematode (drug effects)</term><term>Setaria Nematode (pathogenicity)</term><term>Stilbenes (chemical synthesis)</term><term>Stilbenes (chemistry)</term><term>Stilbenes (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Apoptose ()</term><term>Caspases (biosynthèse)</term><term>Caspases (métabolisme)</term><term>Espèces réactives de l'oxygène (métabolisme)</term><term>Filariose lymphatique (métabolisme)</term><term>Filariose lymphatique (parasitologie)</term><term>Filariose lymphatique (traitement médicamenteux)</term><term>Fragmentation de l'ADN ()</term><term>Humains</term><term>Peroxyde d'hydrogène (métabolisme)</term><term>Régulation de l'expression des gènes ()</term><term>Setaria (nématode) ()</term><term>Setaria (nématode) (pathogénicité)</term><term>Stilbènes ()</term><term>Stilbènes (pharmacologie)</term><term>Stilbènes (synthèse chimique)</term><term>Stress oxydatif ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Caspases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Stilbenes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Stilbenes</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Caspases</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>DNA Fragmentation</term><term>Gene Expression Regulation</term><term>Oxidative Stress</term><term>Setaria Nematode</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Caspases</term><term>Elephantiasis, Filarial</term><term>Hydrogen Peroxide</term><term>Reactive Oxygen Species</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Caspases</term><term>Espèces réactives de l'oxygène</term><term>Filariose lymphatique</term><term>Peroxyde d'hydrogène</term></keywords><keywords scheme="MESH" qualifier="parasitologie" xml:lang="fr"><term>Filariose lymphatique</term></keywords><keywords scheme="MESH" qualifier="parasitology" xml:lang="en"><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Setaria Nematode</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Setaria (nématode)</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Stilbènes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Stilbenes</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Stilbènes</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Filariose lymphatique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Apoptose</term><term>Fragmentation de l'ADN</term><term>Humains</term><term>Régulation de l'expression des gènes</term><term>Setaria (nématode)</term><term>Stilbènes</term><term>Stress oxydatif</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lymphatic filariasis, affecting around 120 million people in 80 countries worldwide, is an extremely painful disease and caused permanent and long term disability. Owing to its alarming prevalence there is immediate need for development of new therapeutics. A series of trans-stilbene derivatives were synthesized using aqueous reaction condition showing potential as antifilarial agents demonstrated in vitro. MTT reduction assay and dye exclusion test were performed to evaluate the micro and macrofilaricidal potential of these compounds. Amid 20 trans-stilbene derivatives together with Resveratrol (RSV), a multifunctional natural product was screened; nine compounds (28, 29, 33, 35, 36, 38, 39, 41 and 42) have showed promising micro and macrofilaricidal activities and four of them (28, 39, 41 and 42) showed better effectiveness than RSV. In the treated parasites apoptosis was established by DNA laddering, in situ DNA fragmentation and FACS analysis. The generation of ROS in the treated parasites was indicated by the depletion in the level of GSH, GR and GST activity and elevation of SOD, catalase, GPx activity and superoxide anion and H2O2 level. Along with the ROS generation and oxidative stress, the decreased expression of anti-apoptotic ced-9 gene and increased expression of nematode specific pro-apoptotic genes, egl-1, ced-4 and ced-3 at the level of transcription and translation level; the up-regulation of caspase-3 activity and involvement of caspase-8,9,3, cytochrome-c and PARP were also observed and which denotes the probable existence of both extrinsic and intrinsic pathways apoptosis in parasitic nematodes. This observation is reported first time and thus it confirmed the mode of action and effectiveness of the compounds. Further, the comparative bioavailability-pharmacokinetics studies showed that compound 28 possesses comparable properties with Ivermectin. This study will certainly intensify our understanding of the pharmacological importance of trans-stilbenes as an anti-filarial agent.</div></front></TEI><affiliations><list><country><li>Inde</li></country></list><tree><country name="Inde"><noRegion><name sortKey="Mukherjee, Niladri" sort="Mukherjee, Niladri" uniqKey="Mukherjee N" first="Niladri" last="Mukherjee">Niladri Mukherjee</name></noRegion><name sortKey="Dutta, Ananya" sort="Dutta, Ananya" uniqKey="Dutta A" first="Ananya" last="Dutta">Ananya Dutta</name><name sortKey="Ghosh, Tamashree" sort="Ghosh, Tamashree" uniqKey="Ghosh T" first="Tamashree" last="Ghosh">Tamashree Ghosh</name><name sortKey="Jana, Kuladip" sort="Jana, Kuladip" uniqKey="Jana K" first="Kuladip" last="Jana">Kuladip Jana</name><name sortKey="Misra, Anup Kumar" sort="Misra, Anup Kumar" uniqKey="Misra A" first="Anup Kumar" last="Misra">Anup Kumar Misra</name><name sortKey="Parida, Pravat Kumar" sort="Parida, Pravat Kumar" uniqKey="Parida P" first="Pravat Kumar" last="Parida">Pravat Kumar Parida</name><name sortKey="Santra, Abhishek" sort="Santra, Abhishek" uniqKey="Santra A" first="Abhishek" last="Santra">Abhishek Santra</name><name sortKey="Sinha Babu, Santi P" sort="Sinha Babu, Santi P" uniqKey="Sinha Babu S" first="Santi P" last="Sinha Babu">Santi P. 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