Effect of Isolated Proteins from Crotalus Durissus Terrificus Venom on Leishmania (Leishmania) Amazonensis-Infected Macrophages

2020 ◽  
Vol 27 (8) ◽  
pp. 718-724 ◽  
Author(s):  
Simone Katz ◽  
Clara Lúcia Barbiéri ◽  
Fernanda Paula Martins Soler ◽  
Andreimar Martins Soares ◽  
Maria Cristina Chavantes ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Inhibitory Effect ◽  
Leishmania Amazonensis ◽  
Significant Activity ◽  
Crotalus Durissus Terrificus ◽  
Mucocutaneous Leishmaniasis ◽  
Potential Alternative ◽  
Etiological Agents ◽  
Crotalus Durissus

Background: Cutaneous and mucocutaneous leishmaniasis are parasitic diseases characterized by skin manifestations. In Brazil, Leishmania (Leishmania) amazonensis is one of the etiological agents of cutaneous leishmaniasis. The therapeutic arsenal routinely employed to treat infected patients is unsatisfactory, especially for pentavalent antimonials, as they are often highly toxic, poorly tolerated and of variable effectiveness. This study aimed to evaluate in vitro the leishmanicidal activity of toxins isolated from Crotalus durissus terrificus venom as a new approach for the treatment of leishmaniasis. Methods: The comparative effects of crotamine, crotoxin, gyrotoxin, convulxin and PLA2 on bone marrow-derived macrophages infected with L. (L.) amazonensis as well as the release of TGF-β from the treated macrophages were studied. Results and Discussion: Crotamine had the strongest inhibitory effect on parasite growth rate (IC50: 25.65±0.52 μg/mL), while convulxin showed the weakest inhibitory effect (IC50: 52.7±2.21 μg/mL). In addition, TGF-β was significantly reduced after the treatment with all toxins evaluated. Conclusion: The Crotalus durissus terrificus toxins used in this study displayed significant activity against L. (L.) amazonensis, indicating that all of them could be a potential alternative for the treatment of cutaneous leishmaniasis.

scholarly journals Selective Effect of 2′,6′-Dihydroxy-4′-Methoxychalcone Isolated from Piper aduncum on Leishmania amazonensis

1999 ◽  
Vol 43 (5) ◽  
pp. 1234-1241 ◽  
Author(s):  
Eduardo Caio Torres-Santos ◽  
Davyson Lima Moreira ◽  
Maria Auxiliadora C. Kaplan ◽  
Maria Nazareth Meirelles ◽  
Bartira Rossi-Bergmann
Keyword(s):  
Simple Structure ◽  
Fluorescein Isothiocyanate ◽  
Inhibitory Effect ◽  
Leishmania Amazonensis ◽  
Significant Activity ◽  
Ultrastructural Studies ◽  
Intracellular Amastigotes ◽  
Effective Doses ◽  
Piper Aduncum

ABSTRACT 2′,6′-Dihydroxy-4′-methoxychalcone (DMC) was purified from the dichloromethane extract of Piper aduncum inflorescences. DMC showed significant activity in vitro against promastigotes and intracellular amastigotes of Leishmania amazonensis, with 50% effective doses of 0.5 and 24 μg/ml, respectively. Its inhibitory effect on amastigotes is apparently a direct effect on the parasites and is not due to activation of the nitrogen oxidative metabolism of macrophages, since the production of nitric oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rather than increased with DMC. The phagocytic activity of macrophages was functioning normally even with DMC concentrations as high as 80 μg/ml, as seen by electron microscopy and by the uptake of fluorescein isothiocyanate-labeled beads. Ultrastructural studies also showed that in the presence of DMC the mitochondria of promastigotes were enlarged and disorganized. Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 μg of DMC/ml. These observations suggest that DMC is selectively toxic to the parasites. Its simple structure may well enable it to serve as a new lead compound for the synthesis of novel antileishmanial drugs.

Evaluating the Effect of Cinnarizine on Promastigotes and Amastigotes forms of Leishmania major

2020 ◽  
Vol 20 (4) ◽  
pp. 550-555 ◽  
Author(s):  
Lima Asgharpour Sarouey ◽  
Parvaneh Rahimi-Moghaddam ◽  
Fatemeh Tabatabaie ◽  
Khadijeh Khanaliha
Keyword(s):  
Flow Cytometry ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Inhibitory Effect ◽  
Control Group ◽  
Secondary Infections ◽  
Ic50 Values ◽  
J774 Cells ◽  
Mtt Assays

: As an important global disease, cutaneous leishmaniasis is associated with complications such as secondary infections and atrophic scars. The first line treatment with antimonials is expensive and reported to have serious side effects and enhance resistance development. The main objective of this study was to evaluate the effect of Cinnarizine on standard strains of Leishmania major because of paucity of information on this subject. Methods: In this experimental study, four concentrations of the drug (5, 10, 15 and 20 μg/ml) were added to Leishmania major cultures at 24, 48 and 72 hours intervals. MTT assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) was ascertained by counting parasites. The inhibitory effect of the drug was compared with that of Glucantime. Flow-cytometry was performed to investigate apoptosis. Each test was repeated thrice. Results: The IC50 values of Cinnarizine after 72 hours were calculated to be 34.76 μg/ml and 23.73 μg/ml for promastigotes and amastigotes, respectively. The results of MTT assays showed 48 % promastigote viability after 72 hour-exposure to Cinnarizine at 20 μg/ml concentration. Programmed cell death in promastigote- and amastigote-infected macrophages was quantified to be 13.66 % and 98.7 %, respectively. Flow- cytometry analysis indicated that Cinnarizine induced early and late apoptosis in parasites. All treatments produced results which differed significantly from control group (P<0.05). Conclusion: Cinnarizine showed low toxicity with anti-leishmanial and apoptosis effects on both promastigote and intracellular amastigote forms. Therefore, we may suggest further assessment on animal models of this drug as candidates for cutaneous leishmaniasis therapy.

scholarly journals 2,4-EPIBRASSIONOLIDE ACTIVATES PRIMING RESISTANCE AGAINST RHIZOPUS STOLONIFER INFECTION IN PEACH FRUIT

2020 ◽  
Vol 49 (2) ◽  
pp. 135-143
Author(s):  
C.H. Li ◽  
M.Y. Du ◽  
K.T. Wang
Keyword(s):  
Fungal Infection ◽  
Inhibitory Effect ◽  
The Other ◽  
Antifungal Compounds ◽  
Rhizopus Stolonifer ◽  
Peach Fruit ◽  
Direct Inhibitory Effect ◽  
Potential Alternative ◽  
Direct Toxicity

This study was conducted to assess the effects of 2,4-epibrassionolide (EBR) on mold decay caused by Rhizopus stolonifer and its capability to activate biochemical defense reactions in postharvest peaches. The treatment of EBR at 5 μM possessed the optimum effectiveness on inhibiting the Rhizopus rot in peach fruit among all treatments. The EBR treatment significantly up-regulated the expression levels of a set of defense-related enzymes and PR genes that included PpCHI, PpGns1, PpPAL, PpNPR1, PpPR1 and PpPR4 as well as led to an enhancement for biosynthesis of phenolics and lignins in peaches during the incubation at 20 °C. Interestingly, the EBR-treated peaches exhibited more striking expressions of PR genes and accumulation of antifungal compounds upon inoculation with the pathogen, indicating a priming defense could be activated by EBR. On the other hand, 5 μM EBR exhibited direct toxicity on fungal proliferation of R. stolonifer in vitro. Thus, we concluded that 5 μM EBR inhibited the Rhizopus rot in peach fruit probably by a direct inhibitory effect on pathogen growth and an indirect induction of a priming resistance. These findings provided a potential alternative for control of fungal infection in peaches during the postharvest storage.

Lipoxygenase-derived eicosanoids are involved in the inhibitory effect of Crotalus durissus terrificus venom or crotoxin on rat macrophage phagocytosis

Toxicon ◽  
2006 ◽  
Vol 47 (3) ◽  
pp. 313-321 ◽  
Author(s):  
S.C. Sampaio ◽  
T.C. Alba-Loureiro ◽  
P. Brigatte ◽  
R.G. Landgraf ◽  
E.C. dos Santos ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Crotalus Durissus Terrificus ◽  
Macrophage Phagocytosis ◽  
Crotalus Durissus

scholarly journals In vivo and in vitro prospection of the anti-ophidic properties exercised by the extracts of Jacaranda decurrens L.

2021 ◽  
Vol 43 ◽  
pp. e57016
Author(s):  
Marcus Vinícius Cardoso Trento ◽  
Mateus Santos Carapiá ◽  
Pedro Henrique Souza César ◽  
Mariana Aparecida Braga ◽  
Andreimar Martins Soares ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Local Effects ◽  
Crotalus Durissus Terrificus ◽  
Mechanism Of Inhibition ◽  
Local Toxicity ◽  
Sds Page ◽  
Crotalus Durissus ◽  
Venom Proteins

The research and development of alternative treatments for snakebites (e.g., medicinal plants) is necessary due to the high costs of the existing ones. The effects of the aqueous extracts from Jacaranda decurrens leaves, roots, and xylopodium were analyzed upon the venom-induced (Bothrops spp. and Crotalus spp.) systemic and local toxicity. The extracts were able to partially inhibit the phospholipase activity of the venoms from Bothrops jararacussu and Crotalus durissus terrificus. The myotoxic, edema-inducing, coagulant, and hemorrhagic activities were also inhibited. The SDS-PAGE showed that the venom proteins were intact after their incubation with the extracts. This suggests that the possible mechanism of inhibition is not related to the degradation of the protein but rather to their binding to specific sites of the enzymes. The extracts significantly prolonged the survival time of animals in the lethality assay performed with Crotalus durissus terrificus venom and its toxin (crotoxin). The anti-ophidic activity of medicinal plants may aid in the management of snakebites in distant locations by reducing the victim’s local effects and time to heal.

scholarly journals Isolation Purification and Partial Characterization of Antisnake Venom Plant Peptide (BRS-P19) from Bauhinia rufescens (LAM FAM) Seed as Potential Alternative to Serum-Based Antivenin

2020 ◽  
pp. 18-26
Author(s):  
I. Sani ◽  
A.A. Umar ◽  
S.A. Jiga ◽  
F. Bello ◽  
A. Abdulhamid ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Research Work ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Untreated Group ◽  
Control Group ◽  
In Vivo Experiments ◽  
Potential Alternative

Several studies have been reported on active peptides isolated from some medicinal plants, which were effective inhibitors against snake venom induced toxicities. Hence, the aim of this research work was to isolate, purify and characterize an antisnake venom plant peptide from Bauhinia rufescens seed that can serve as potential alternative to serum-based antivenins. B. rufescens seed was collected, duly identified, authenticated and processed. The peptide was isolated from the seed and purified using gel filtration chromatography and SDS-PAGE and then named as BRS-P19. Venom Phospholipase A2 (VPLA2) was used for the study and was isolated from Naja nigricollis venom. Albino mice of both sexes were used for in vivo experiments. They were divided into seven (7) groups of three (3) mice each. Group 1 served as normal control, group 2 were injected with VPLA2 only, group 3 and 4 were injected with VPLA2 then treated with BRS-P19 at doses of 0.2 and 0.4 mg/kg b.w. respectively, while mice in group 5 were injected with VPLA2 then treated with standard antivenin, group 6 and 7 were injected with VPLA2 followed by administration of ascorbic acid and α-tocopherol respectively. In all the groups, hepatic and renal levels of reactive oxygen species (ROS), lipid peroxidation (MDA) and activities of antioxidant enzymes were determined. The results showed that, the BRS-P19 has molecular weight of ~19kD. Its percentage in vitro inhibitory effect against VPLA2 was 91.85 ± 0.32%. For the in vivo study, the animals treated with 0.4 mg/kg b.w. of the BRS-P19 showed a significant (P<0.05) decrease in the hepatic and renal ROS and MDA levels when compared with the VPLA2 untreated group. But, the activities of the antioxidant enzymes in all the treated groups were significantly (P<0.05) increased by the BRS-P19 at 0.4 mg/kg b.w. when compared to the VPLA2 untreated group. Based on these findings, it has been established that, BRS-P19 has antisnake venom effect through inhibition of VPLA2 and antioxidant activity as the possible mechanisms of action.

scholarly journals Inhibition of proteases and phospholipases A2 from Bothrops atrox and Crotalus durissus terrificus snake venoms by ascorbic acid, vitamin E, and B-complex vitamins

2016 ◽  
Vol 88 (3 suppl) ◽  
pp. 2005-2016 ◽  
Author(s):  
CARLOS H.M. OLIVEIRA ◽  
ANDERSON A. SIMÃO ◽  
MARCUS V.C. TRENTO ◽  
PEDRO H.S. CÉSAR ◽  
SILVANA MARCUSSI
Keyword(s):  
Vitamin E ◽  
Low Cost ◽  
Crotalus Durissus Terrificus ◽  
Phospholipases A2 ◽  
Antioxidant Mechanism ◽  
Valuable Adjunct ◽  
B Complex Vitamins ◽  
Crotalus Durissus ◽  
Bothrops Atrox

ABSTRACT The enzyme inhibition by natural and/ or low-cost compounds may represent a valuable adjunct to traditional serotherapy performed in cases of snakebite, mainly with a view to mitigate the local effects of envenoming. The objective of this study was to evaluate possible interactions between vitamins and enzymes that comprise Bothrops atrox and Crotalus durissus terrificus venoms, in vitro. Proteolysis inhibition assays (substrates: azocasein, collagen, gelatin and fibrinogen), hemolysis, coagulation, hemagglutination were carried out using different proportions of vitamins in face of to inhibit minimum effective dose of each venom. The vitamins were responsible for reducing 100% of breaking azocasein by C.d.t. venom, thrombolysis induced by B. atrox and fibrinogenolysis induced by both venoms. It is suggested the presence of interactions between vitamin and the active site of enzymes, for example the interactions between hydrophobic regions present in the enzymes and vitamin E, as well as the inhibitions exercised by antioxidant mechanism.

Contribution of crotoxin for the inhibitory effect of Crotalus durissus terrificus snake venom on macrophage function

Toxicon ◽  
2003 ◽  
Vol 41 (7) ◽  
pp. 899-907 ◽  
Author(s):  
S.C Sampaio ◽  
P Brigatte ◽  
M.C.C Sousa-e-Silva ◽  
E.C dos-Santos ◽  
A.C Rangel-Santos ◽  
...  
Keyword(s):  
Snake Venom ◽  
Inhibitory Effect ◽  
Crotalus Durissus Terrificus ◽  
Macrophage Function ◽  
Crotalus Durissus

scholarly journals Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Angela Maria Arenas Velásquez ◽  
Willian Campos Ribeiro ◽  
Vutey Venn ◽  
Silvia Castelli ◽  
Mariana Santoro de Camargo ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Parasite Load ◽  
Inhibitory Effect ◽  
Peritoneal Macrophages ◽  
Leishmania Amazonensis ◽  
Content Type ◽  
Intracellular Amastigotes ◽  
Therapeutic Alternatives

ABSTRACT Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. We report here the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N′-dimethylbenzylamine (Hdmba) against Leishmania amazonensis. The compound [Pd(dmba)(μ-N3)]2 (CP2) inhibits promastigote growth (50% inhibitory concentration [IC50] = 13.2 ± 0.7 μM) and decreases the proliferation of intracellular amastigotes in in vitro incubated macrophages (IC50 = 10.2 ± 2.2 μM) without a cytotoxic effect when tested against peritoneal macrophages (50% cytotoxic concentration = 506.0 ± 10.7 μM). In addition, CP2 was also active against T. cruzi intracellular amastigotes (IC50 = 2.3 ± 0.5 μM, selective index = 225), an indication of its potential for use in Chagas disease therapy. In vivo assays using L. amazonensis-infected BALB/c showed an 80% reduction in parasite load compared to infected and nontreated animals. Also, compared to amphotericin B treatment, CP2 did not show any side effects, which was corroborated by the analysis of plasma levels of different hepatic and renal biomarkers. Furthermore, CP2 was able to inhibit Leishmania donovani topoisomerase 1B (Ldtopo1B), a potentially important target in this parasite. (This study has been registered at ClinicalTrials.gov under identifier NCT02169141.)

American Leishmania spp: Formycin B treatment of cutaneous leishmaniasis in mice

Parasitology ◽  
1987 ◽  
Vol 94 (3) ◽  
pp. 467-474 ◽  
Author(s):  
Tamara Rojas ◽  
J. L. Avila
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Optimal Dose ◽  
Dose Schedule ◽  
Inhibitory Effect ◽  
American Cutaneous Leishmaniasis ◽  
Leishmania Spp ◽  
Low Toxicity ◽  
Foot Pad

Using foot-pad infection of female C57BL/6, DBA/2J and NMRI-IVIC mice as an animal model for American cutaneous leishmaniasis (ACL), we evaluated the inhibitory effect of Formycin B (FoB) on the infection produced by 7 different Leishmania isolates. When treatment was initiated some days, or even some weeks, after infection a significant leishmanistatic effect was detected on mice infected with all Leishmania isolates, which reached 30–55 weeks for some isolates. The optimal dose schedule was 1·25 mg/kg body weight/day, injected intraperitoneally for 20 consecutive days. Significant differences in the sensitivity of various Leishmania spp. to FoB were found, either in vivo, or in vitro where a high [3H]FoB incorporation rate was found only for certain Leishmania isolates. The low toxicity of this drug and the sensitivity of the 7 Leishmania isolates tested suggest that FoB could be useful in the treatment of ACL.

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