Synthetic single and double aza-scorpiand macrocycles acting as inhibitors of the antioxidant enzymes iron superoxide dismutase and trypanothione reductase in Trypanosoma cruzi with promising results in a murine model

RSC Advances ◽  
2014 ◽  
Vol 4 (110) ◽  
pp. 65108-65120 ◽  
Author(s):  
F. Olmo ◽  
M. P. Clares ◽  
C. Marín ◽  
J. González ◽  
M. Inclán ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Survival Rate ◽  
Trypanosoma Cruzi ◽  
Murine Model ◽  
Trypanothione Reductase ◽  
Iron Superoxide Dismutase

Synthetic scorpiand-like azamacrocycles selectively inhibit SOD and TR enzymes of Trypanosoma cruzi in mice causing death of the parasites and increasing the mouse survival rate after infection and treatment.

Efficient Inhibition of Iron Superoxide Dismutase and of Trypanosoma cruzi Growth by Benzo[g]phthalazine Derivatives Functionalized with One or Two Imidazole Rings

2008 ◽  
Vol 51 (6) ◽  
pp. 1962-1966 ◽  
Author(s):  
Ana M. Sanz ◽  
Fernando Gómez-Contreras ◽  
Pilar Navarro ◽  
Manuel Sánchez-Moreno ◽  
Samira Boutaleb-Charki ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Trypanosoma Cruzi ◽  
Iron Superoxide Dismutase

scholarly journals An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase

2015 ◽  
Vol 5 (3) ◽  
pp. 110-116 ◽  
Author(s):  
Francisco Olmo ◽  
Kristína Urbanová ◽  
Maria Jose Rosales ◽  
Ruben Martín-Escolano ◽  
Manuel Sánchez-Moreno ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Mouse Model ◽  
Trypanosoma Cruzi ◽  
Acute Phase ◽  
Iron Superoxide Dismutase

scholarly journals Mitochondrial superoxide radicals mediate programmed cell death in Trypanosoma cruzi: cytoprotective action of mitochondrial iron superoxide dismutase overexpression

2007 ◽  
Vol 403 (2) ◽  
pp. 323-334 ◽  
Author(s):  
Lucía Piacenza ◽  
Florencia Irigoín ◽  
María Noel Alvarez ◽  
Gonzalo Peluffo ◽  
Martin C. Taylor ◽  
...  
Keyword(s):  
Cell Death ◽  
Superoxide Dismutase ◽  
Programmed Cell Death ◽  
Trypanosoma Cruzi ◽  
Early Period ◽  
Pentose Phosphate ◽  
Iron Superoxide Dismutase ◽  
Mitochondrial Superoxide ◽  
Glucose Flux ◽  
Mitochondrial Aconitase

Trypanosoma cruzi undergo PCD (programmed cell death) under appropriate stimuli, the mechanisms of which remain to be established. In the present study, we show that stimulation of PCD in T. cruzi epimastigotes by FHS (fresh human serum) results in rapid (<1 h) externalization of phosphatidylserine and depletion of the low molecular mass thiols dihydrotrypanothione and glutathione. Concomitantly, enhanced generation of oxidants was established by EPR and immuno-spin trapping of radicals using DMPO (5,5-dimethylpyrroline-N-oxide) and augmentation of the glucose flux through the pentose phosphate pathway. In the early period (<20 min), changes in mitochondrial membrane potential and inhibition of respiration, probably due to the impairment of ADP/ATP exchange with the cytosol, were observed, conditions that favour the generation of O2•−. Accelerated rates of mitochondrial O2•− production were detected by the inactivation of the redox-sensitive mitochondrial aconitase and by oxidation of a mitochondrial-targeted probe (MitoSOX). Importantly, parasites overexpressing mitochondrial FeSOD (iron superoxide dismutase) were more resistant to the PCD stimulus, unambiguously indicating the participation of mitochondrial O2•− in the signalling process. In summary, FHS-induced PCD in T. cruzi involves mitochondrial dysfunction that causes enhanced O2•− formation, which leads to cellular oxidative stress conditions that trigger the initiation of PCD cascades; moreover, overexpression of mitochondrial FeSOD, which is also observed during metacyclogenesis, resulted in cytoprotective effects.

scholarly journals Buthionine Sulfoximine Has Anti-Trypanosoma cruzi Activity in a Murine Model of Acute Chagas' Disease and Enhances the Efficacy of Nifurtimox

2008 ◽  
Vol 52 (5) ◽  
pp. 1837-1839 ◽  
Author(s):  
Mario Faúndez ◽  
Rodrigo López-Muñoz ◽  
Gloria Torres ◽  
Antonio Morello ◽  
Jorge Ferreira ◽  
...  
Keyword(s):  
Body Weight ◽  
Survival Rate ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Murine Model ◽  
Parasite Burden ◽  
Buthionine Sulfoximine ◽  
Acute Chagas Disease

ABSTRACT l-Buthionine (S,R)-sulfoximine (BSO) at a dose of 220 mg/kg of body weight/day showed an anti-Trypanosoma cruzi effect in infected mice, increasing their survival rate and decreasing the parasitemias and parasite burden in the hearts. Treatment with BSO plus nifurtimox caused an increase in the survival rate in comparison to the rates with treatment with each drug alone.

Cereals frost resistance correlates with an integral indicators of content of low-molecular-weight protective compounds and activity of antioxidant enzymes

2020 ◽  
Vol 2020 (3) ◽  
pp. 71-86
Author(s):  
O. I. Horielova ◽  
◽  
N. I. Ryabchun ◽  
M. A. Shkliarevskyi ◽  
A. M. Reznik ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Antioxidant System ◽  
Frost Resistance ◽  
Low Molecular Weight ◽  
Guaiacol Peroxidase ◽  
Wheat Seedlings ◽  
Enzymatic Antioxidant ◽  
Adult Plants

Along with specific adaptive reactions, universal defense reactions, in particular activation of antioxidant system, are of great importance for plant survival under cold conditions. We have studied a relationship among the content of low-molecular-weight protective compounds with antioxidant properties (proline, soluble carbohydrates, flavonoids), the activity of antioxidant enzymes (superoxide dismutase, catalase, and guaiacol peroxidase) in seedlings of winter wheat, rye and triticale, and frost resistance of etiolated seedlings and adult plants at tillering stage. It was found that there was a fairly close correlation between the frost resistance of seedlings and adult cereal plants (r = 0,78). It was shown that a pronounced relationship between individual indicators of antioxidant system functioning in unhardened seedlings and their frost resistance was not found. After 6-day hardening of seedlings at 2-4°C, there was a high correlation between the total indicator of the enzymatic antioxidant system (the sum of normalized indicators of superoxide dismutase, peroxidase, and catalase activity) and their frost resistance (r = 0,86), but the correlation coefficient of this index with frost resistance of plants in tillering phase was significantly lower (r = 0,47). At the same time, a high correlation was found between the content of low-molecular-weight protectors in hardened seedlings and frost resistance of tillering adult plants (r = 0.89). The closest correlation was observed between the integral normalized indicator, comprising the sum of normalized values of antioxidant enzymes activity and the content of low-molecular-weight protectors in hardened seedlings, and frost resistance of seedlings (r = 0,94) and plants in tillering phase (r = 0,89). A presence of specific features in the functioning of antioxidant system during cold adaptation of cereal seedlings was established. Rye is characterized by a high content of low-molecular-weight protective compounds; at the same time, increased activity of antioxidant enzymes - superoxide dismutase and catalase - was noted in wheat seedlings. In triticale, depending on the genotype, the values of both enzymatic antioxidant activity and the content of low-molecular-weight protectors varied.

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