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Further evidence of the trypanocidal action of eupomatenoid-5: confirmation of involvement of reactive oxygen species and mitochondria owing to a reduction in trypanothione reductase activity.
Free Radic Biol Med. 2013 Jul; 60:17-28.FR

Abstract

Our group assays natural products that are less toxic and more effective than available nitroheterocycles as promising therapeutic options for patients with Chagas disease. Our previous study reported the trypanocidal activity of eupomatenoid-5, a neolignan isolated from the leaves of Piper regnellii var. pallescens, against the three main parasitic forms of Trypanosoma cruzi. The present study further characterizes the biochemical and morphological alterations induced by this compound to elucidate the mechanisms of action involved in the cell death of T. cruzi. We show that eupomatenoid-5 induced oxidative imbalance in the three parasitic forms, especially trypomastigotes, reflected by a decrease in the activity of trypanothione reductase and increase in the formation of reactive oxygen species (ROS). A reduction of mitochondrial membrane potential was then triggered, further impairing the cell redox system through the production of more ROS and reactive nitrogen species. Altogether, these effects led to oxidative stress, reflected by lipid peroxidation and DNA fragmentation. These alterations are key events in the induction of parasite death through various pathways, including apoptosis, necrosis, and autophagy.

Authors+Show Affiliations

Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, 87020-900 Maringá, PR, Brasil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23376033

Citation

Lazarin-Bidóia, D, et al. "Further Evidence of the Trypanocidal Action of Eupomatenoid-5: Confirmation of Involvement of Reactive Oxygen Species and Mitochondria Owing to a Reduction in Trypanothione Reductase Activity." Free Radical Biology & Medicine, vol. 60, 2013, pp. 17-28.
Lazarin-Bidóia D, Desoti VC, Ueda-Nakamura T, et al. Further evidence of the trypanocidal action of eupomatenoid-5: confirmation of involvement of reactive oxygen species and mitochondria owing to a reduction in trypanothione reductase activity. Free Radic Biol Med. 2013;60:17-28.
Lazarin-Bidóia, D., Desoti, V. C., Ueda-Nakamura, T., Dias Filho, B. P., Nakamura, C. V., & Silva, S. O. (2013). Further evidence of the trypanocidal action of eupomatenoid-5: confirmation of involvement of reactive oxygen species and mitochondria owing to a reduction in trypanothione reductase activity. Free Radical Biology & Medicine, 60, 17-28. https://doi.org/10.1016/j.freeradbiomed.2013.01.008
Lazarin-Bidóia D, et al. Further Evidence of the Trypanocidal Action of Eupomatenoid-5: Confirmation of Involvement of Reactive Oxygen Species and Mitochondria Owing to a Reduction in Trypanothione Reductase Activity. Free Radic Biol Med. 2013;60:17-28. PubMed PMID: 23376033.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Further evidence of the trypanocidal action of eupomatenoid-5: confirmation of involvement of reactive oxygen species and mitochondria owing to a reduction in trypanothione reductase activity. AU - Lazarin-Bidóia,D, AU - Desoti,V C, AU - Ueda-Nakamura,T, AU - Dias Filho,B P, AU - Nakamura,C V, AU - Silva,S O, Y1 - 2013/01/31/ PY - 2012/11/05/received PY - 2013/01/11/accepted PY - 2013/2/5/entrez PY - 2013/2/5/pubmed PY - 2013/11/2/medline SP - 17 EP - 28 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 60 N2 - Our group assays natural products that are less toxic and more effective than available nitroheterocycles as promising therapeutic options for patients with Chagas disease. Our previous study reported the trypanocidal activity of eupomatenoid-5, a neolignan isolated from the leaves of Piper regnellii var. pallescens, against the three main parasitic forms of Trypanosoma cruzi. The present study further characterizes the biochemical and morphological alterations induced by this compound to elucidate the mechanisms of action involved in the cell death of T. cruzi. We show that eupomatenoid-5 induced oxidative imbalance in the three parasitic forms, especially trypomastigotes, reflected by a decrease in the activity of trypanothione reductase and increase in the formation of reactive oxygen species (ROS). A reduction of mitochondrial membrane potential was then triggered, further impairing the cell redox system through the production of more ROS and reactive nitrogen species. Altogether, these effects led to oxidative stress, reflected by lipid peroxidation and DNA fragmentation. These alterations are key events in the induction of parasite death through various pathways, including apoptosis, necrosis, and autophagy. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/23376033/Further_evidence_of_the_trypanocidal_action_of_eupomatenoid_5:_confirmation_of_involvement_of_reactive_oxygen_species_and_mitochondria_owing_to_a_reduction_in_trypanothione_reductase_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(13)00009-9 DB - PRIME DP - Unbound Medicine ER -