Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole
Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2009-01-01
|
| Series: | Journal of Parasitology Research |
| Online Access: | http://dx.doi.org/10.1155/2009/463575 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832549571674243072 |
|---|---|
| author | Annamaria Buschini Lisa Ferrarini Susanna Franzoni Serena Galati Mirca Lazzaretti Francesca Mussi Cristina Northfleet de Albuquerque Tânia Maria Araújo Domingues Zucchi Paola Poli |
| author_facet | Annamaria Buschini Lisa Ferrarini Susanna Franzoni Serena Galati Mirca Lazzaretti Francesca Mussi Cristina Northfleet de Albuquerque Tânia Maria Araújo Domingues Zucchi Paola Poli |
| author_sort | Annamaria Buschini |
| collection | DOAJ |
| description | Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells. |
| format | Article |
| id | doaj-art-402fb07236374fe98421e96be2cc5d9e |
| institution | Kabale University |
| issn | 2090-0023 2090-0031 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Parasitology Research |
| spelling | doaj-art-402fb07236374fe98421e96be2cc5d9e2025-02-03T06:10:52ZengWileyJournal of Parasitology Research2090-00232090-00312009-01-01200910.1155/2009/463575463575Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and MetronidazoleAnnamaria Buschini0Lisa Ferrarini1Susanna Franzoni2Serena Galati3Mirca Lazzaretti4Francesca Mussi5Cristina Northfleet de Albuquerque6Tânia Maria Araújo Domingues Zucchi7Paola Poli8Dipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, Università di Parma, Parco Area delle Scienze, 11/a, 43100 Parma, ItalyDipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, Università di Parma, Parco Area delle Scienze, 11/a, 43100 Parma, ItalyDipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, Università di Parma, Parco Area delle Scienze, 11/a, 43100 Parma, ItalyDipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, Università di Parma, Parco Area delle Scienze, 11/a, 43100 Parma, ItalyDipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, Università di Parma, Parco Area delle Scienze, 11/a, 43100 Parma, ItalyDipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, Università di Parma, Parco Area delle Scienze, 11/a, 43100 Parma, ItalyDepartamento de Tecnologia Bioquímico Farmacêutica, Faculdade de Ciências Farmacêuticas, USP, Avenida Prof. Lineu Prestes, 580, Cidade Universitária, 05508-900 São Paulo, BrazilDepartamento de Parasitologia, Instituto de Ciências Biomédicas, USP, Avenida Prof. Lineu Prestes, 1374, Cidade Universitária, 05508-900 São Paulo, BrazilDipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, Università di Parma, Parco Area delle Scienze, 11/a, 43100 Parma, ItalyNitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells.http://dx.doi.org/10.1155/2009/463575 |
| spellingShingle | Annamaria Buschini Lisa Ferrarini Susanna Franzoni Serena Galati Mirca Lazzaretti Francesca Mussi Cristina Northfleet de Albuquerque Tânia Maria Araújo Domingues Zucchi Paola Poli Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole Journal of Parasitology Research |
| title | Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole |
| title_full | Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole |
| title_fullStr | Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole |
| title_full_unstemmed | Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole |
| title_short | Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole |
| title_sort | genotoxicity revaluation of three commercial nitroheterocyclic drugs nifurtimox benznidazole and metronidazole |
| url | http://dx.doi.org/10.1155/2009/463575 |
| work_keys_str_mv | AT annamariabuschini genotoxicityrevaluationofthreecommercialnitroheterocyclicdrugsnifurtimoxbenznidazoleandmetronidazole AT lisaferrarini genotoxicityrevaluationofthreecommercialnitroheterocyclicdrugsnifurtimoxbenznidazoleandmetronidazole AT susannafranzoni genotoxicityrevaluationofthreecommercialnitroheterocyclicdrugsnifurtimoxbenznidazoleandmetronidazole AT serenagalati genotoxicityrevaluationofthreecommercialnitroheterocyclicdrugsnifurtimoxbenznidazoleandmetronidazole AT mircalazzaretti genotoxicityrevaluationofthreecommercialnitroheterocyclicdrugsnifurtimoxbenznidazoleandmetronidazole AT francescamussi genotoxicityrevaluationofthreecommercialnitroheterocyclicdrugsnifurtimoxbenznidazoleandmetronidazole AT cristinanorthfleetdealbuquerque genotoxicityrevaluationofthreecommercialnitroheterocyclicdrugsnifurtimoxbenznidazoleandmetronidazole AT taniamariaaraujodomingueszucchi genotoxicityrevaluationofthreecommercialnitroheterocyclicdrugsnifurtimoxbenznidazoleandmetronidazole AT paolapoli genotoxicityrevaluationofthreecommercialnitroheterocyclicdrugsnifurtimoxbenznidazoleandmetronidazole |