Planta Med 2009; 75 - PD16
DOI: 10.1055/s-0029-1234495

Identification of the mechanism of action of eupomatenoid-5 isolated from Piper regnellii var. pallescens on Trypanosoma cruzi

KJP Rocha 1, P Veiga-Santos 2, SO Silva 3, T Ueda-Nakamura 2, 3, BP Dias Filho 1, 2, 3, VF Ximenes 4, CV Nakamura 1, 2, 3
  • 1Pós Graduação em Microbiologia, Universidade Estadual de Londrina, 86055–990, Londrina – PR, Brasil
  • 2Pós Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, 87020–900, Maringá – PR, Brasil
  • 3Departamento de Analises Clinicas, Universidade Estadual de Maringá, 87020–900, Maringá – PR, Brasil
  • 4Departamento de Química, Faculdade de Ciências, UNESP, 17033–360, Bauru – SP, Brasil

Parasitic protozoa cause several diseases, affecting hundreds of millions, particularly in underdeveloped countries [1]. Chagas disease is one of these clinical conditions triggered by infection with the protozoan Trypanosoma cruzi. The currently drugs available for treatment of this infection are unsatisfactory due to limited efficacy and toxic side effects, making the search for more specific pharmacological agents a priority [2]. In previous work, eupomatenoid-5 isolated from Piper regnellii var. pallescens showed activity against the proliferative stages of T. cruzi [3]. Here, we decided to investigate the mechanism of action of the eupomatenoid-5 on T. cruzi. The components of the trypanothione-dependent antioxidant system from T. cruzi have been pointed out as potential chemotherapeutic targets [2] by presenting differences with mammalian host. Thus, epimastigotes were pre-treated with eupomatenoid-5 and challenged with doses of H2O2 in IB medium. Then, the cells were resuspended in LIT medium and the growth index (GI) determined after 5 days. Control of the eupomatenoid-5 and H2O2 were also performed. For lipoperoxidation assay, the same treatment was performed and determined as the amount of thiobarbituric acid-reactive substances in terms of malondialdehyde [4]. The results showed a decrease of GI after pre-treatment and challenged with non-toxic dose (20mM) (35.4%) and sub-lethal dose of H2O2 (100mM) (17.9%), while the control eupomatenoid-5 GI was 61.5%. Additionally, the same treatment increased lipoperoxidation compared with the controls H2O2 and eupomatenoid-5. These results have indicated that eupomatenoid-5 can act in the detoxification system of T. cruzi making these cells more susceptive to H2O2. Studies in trypomastigote and amastigote intracellular forms are being performed.

Acknowledgements: This study was supported through grants from DECIT/SCTIE/MS and MCT by CNPq, FINEP, PRONEX/Fund. Araucária.

References: [1] Turrens, J.F. (2004) Mol. Aspects Med. 25:211–220.

[2] Mielniczki-Pereira, A.A. et al. (2007) Acta Trop. 101:54–60.

[3] Luize, P.S. et al. (2006) Biol. Pharm. Bull. 29:2126–2130.

[4] Hernández, S.M. et al. (2006) Acta Trop. 98:94–102