HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Concomitant Benznidazole and Suramin Chemotherapy in Mice Infected with a Virulent Strain of Trypanosoma cruzi.

Abstract
Although suramin (Sur) is suggested as a potential drug candidate in the management of Chagas disease, this issue has not been objectively tested. In this study, we examined the applicability of concomitant treatment with benznidazole (Bz) and suramin in mice infected with a virulent strain of Trypanosoma cruzi. Eighty 12-week-old male C57BL/6 mice were equally randomized in eight groups: (i) noninfected mice (negative control) and mice infected with T. cruzi Y strain receiving (ii) no treatment (positive control), (iii) Bz, 100 mg/kg of body weight per day, (iv) Sur, 20 mg/kg/day, and (v to viii) Sur, 20 mg/kg/day, combined with Bz, 100, 50, 25, or 5 mg/kg/day. Bz was administered by gavage, and Sur was administered intraperitoneally. Sur dramatically increased the parasitemia, cardiac content of parasite DNA, inflammation, oxidative tissue damage, and mortality. In response to high parasitic load in cardiac tissue, Sur stimulated the immune system in a manner typical of the acute phase of Chagas disease, increasing tissue levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) and inducing a preferential IgG2a anti-T. cruzi serum pattern. When Sur and Bz were combined, the infection severity was attenuated, showing a dose-dependent Bz response. Sur therapy had a more harmful effect on the host than on the parasite and reduced the efficacy of Bz against T. cruzi infection. Considering that Sur drastically reinforced the infection evolution, potentiating the inflammatory process and the severity of cardiac lesions, the in vivo findings contradicted the in vitro anti-T. cruzi potential described for this drug.
AuthorsEliziária C Santos, Rômulo D Novaes, Marli C Cupertino, Daniel S S Bastos, Raphael C Klein, Eduardo A M Silva, Juliana L R Fietto, André Talvani, Maria T Bahia, Leandro L Oliveira
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 10 Pg. 5999-6006 (Oct 2015) ISSN: 1098-6596 [Electronic] United States
PMID26169419 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Antibodies, Protozoan
  • Immunoglobulin G
  • Nitroimidazoles
  • Trypanocidal Agents
  • Tumor Necrosis Factor-alpha
  • Suramin
  • Interferon-gamma
  • benzonidazole
Topics
  • Administration, Oral
  • Animals
  • Antibodies, Protozoan (biosynthesis)
  • Chagas Disease (drug therapy, immunology, mortality, parasitology)
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Immunoglobulin G (biosynthesis)
  • Injections, Intraperitoneal
  • Interferon-gamma (biosynthesis)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitroimidazoles (antagonists & inhibitors, pharmacology)
  • Parasite Load
  • Suramin (adverse effects)
  • Survival Analysis
  • Trypanocidal Agents (pharmacology)
  • Trypanosoma cruzi (drug effects, growth & development, pathogenicity)
  • Tumor Necrosis Factor-alpha (biosynthesis)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: