Biodegradable Microparticles Containing Crotamine Isolated from &lt;b&gt;&lt;i&gt;Crotalus durissus terrificus&lt;/i&gt;&lt;/b&gt; Display Antileishmanial Activity in vitro

Macedo, Sharon Rose Aragão; Barros, Neuza Biguinati de; Ferreira, Amália S.; Moreira-Dill, Leandro S.; Calderon, Leonardo de Azevedo; Soares, Andreimar M.; Nicolete, Roberto

doi:10.1159/000371391

Cited by 23 publications

(9 citation statements)

References 22 publications

(35 reference statements)

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“…Several studies have demonstrated the antibiotic activity of C. d. terrificus venom against different bacteria (28,29) . Other studies have shown that the venom has antiviral activity against dengue fever, yellow fever (30) , and human immunodeficiency virus (31) , antiprotozoal activity against Leishmania amazonensis (32) and Giardia duodenalis (33) , and antifungal activity against Candida spp., Trichosporon spp., and Cryptococcus neoformans (28) .…”

Section: Resultsmentioning

confidence: 99%

EVALUATION OF THE ANTIBACTERIAL ACTIVITY OF Crotalus durissus terrificus CRUDE VENOM

et al. 2018

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Snake venoms are recognized as a promising source of pharmacologically active substances and are potentially useful for the development of new antimicrobial drugs. This study aimed to investigate the antimicrobial activity of the venom from the rattlesnake Crotalus durissus terrificus against several bacteria. Antibacterial activity was determined by using the plate microdilution method and the activity on the bacterial envelope structure was screened by using the crystal violet assay. The proteins in crude venom were separated by electrophoresis and characterized regarding their proteolytic activity. C. d. terrificus venom exhibited antimicrobial action against gram-positive and gram-negative bacteria. MIC values were defined for Pseudomonas aeruginosa ATCC 27853 (62.5 µg/mL), Staphylococcus aureus ATCC 25923 (125 µg/mL), and Micrococcus luteus ATCC 9341 (≤500 µg/mL). For Salmonella enterica serovar typhimurium ATCC 14028 and Corynebacterium glutamicum ATCC 13032, the decrease in bacterial growth was not detected visually, but was statistically significant. The crystal violet assay demonstrated that the crude venom increased bacterial cell permeability and the secreted protein profile agreed with previous reports. The results suggest that the proteins with lytic activity against bacteria in C. d. terrificus venom deserve further characterization as they may offer reinforcements to the weak therapeutic arsenal used to fight microbial multidrug resistance.

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Section: Resultsmentioning

confidence: 99%

EVALUATION OF THE ANTIBACTERIAL ACTIVITY OF Crotalus durissus terrificus CRUDE VENOM

et al. 2018

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“…The pharmacological properties of crotamine on different biological models include its analgesic potential [16], insulin release potential [11], memory persistence enhancement without psychomotor alterations [44] and antimicrobial and antiparasitic actions in several species [5,12,13,14,15,23]. Moreover, due to its cell-penetrating capacity and site-specific interactions, crotamine has been studied as a drug-mediating peptide and as a model for the discovery of new antitumor molecules [10,17,19,21,22,23].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to its toxic effect, crotamine has been shown to potentiate insulin release [11] and to have a strong antimicrobial activity [9,12,13,14,15]. Other properties, still poorly understood, include analgesic and hemolytic activities, as well as stimulation of the immune system by interfering with the activity of mast cells, macrophages, lymphocytes and monocytes.…”

Section: Introductionmentioning

confidence: 99%

Intradermal Application of Crotamine Induces Inflammatory and Immunological Changes In Vivo

Silvestrini

Macedo

Andrade

et al. 2019

Toxins

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Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty male Wistar rats were intradermically injected with 200, 400 and 800 µg crotamine and analyzed after 1, 3 and 7 days. Local effect of crotamine was assessed by determination of MPO and NAG activities, NO levels and angiogenesis. Systemic inflammatory response was assessed by determination of IL-10, TNF-α, CRP, NO, TBARS and SH groups. Crotamine induced macrophages and neutrophils chemotaxis as evidenced by the upregulation of both NAG (0.5–0.6 OD/mg) and MPO (0.1–0.2 OD/mg) activities, on the first and third day of analysis, respectively. High levels of NO were observed for all concentrations and time-points. Moreover, 800 μg crotamine resulted in serum NO (64.7 μM) and local tissue NO (58.5 μM) levels higher or equivalent to those recorded for their respective histamine controls (55.7 μM and 59.0 μM). Crotamine also induced a significant angiogenic response compared to histamine. Systemically, crotamine induced a progressive increase in serum CRP levels up to the third day of analysis (22.4–45.8 mg/mL), which was significantly greater than control values. Crotamine (400 μg) also caused an increase in serum TNF-α, in the first day of analysis (1095.4 pg/mL), however a significant increase in IL-10 (122.2 pg/mL) was also recorded for the same time-point, suggesting the induction of an anti-inflammatory effect. Finally, crotamine changed the systemic redox state by inducing gradual increase in serum levels of TBARS (1.0–1.8 μM/mL) and decrease in SH levels (124.7–19.5 μM/mL) throughout the experimental period of analysis. In summary, rats intradermally injected with crotamine presented local and systemic acute inflammatory responses similarly to histamine, which limits crotamine therapeutic use on its original form.

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“…Interestingly, Furtado et al (2014) obtained similar results when they treated J774A.1 macrophages with a Bothrops atrox -derived toxin. However, Macedo et al (2015) studied the effect of crotamine, another toxin derived from Cdt venom, and did not observe any antileishmanial activity after treating infected peritoneal macrophages with up to 100 µ g mL −1 of the toxin. Thus, the higher phagocytic capacity induced by CTX in macrophages that were challenged with Leishmania parasites after 24 h appears to induce the destruction of the intracellular amastigotes after 48 h of treatment, and this is directly related to the development of an effective immune response.…”

Section: Discussionmentioning

confidence: 99%

Crotoxin stimulates anM1activation profile in murine macrophages duringLeishmania amazonensisinfection

et al. 2017

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American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.

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Biodegradable Microparticles Containing Crotamine Isolated from <b><i>Crotalus durissus terrificus</i></b> Display Antileishmanial Activity in vitro

Cited by 23 publications

References 22 publications

EVALUATION OF THE ANTIBACTERIAL ACTIVITY OF Crotalus durissus terrificus CRUDE VENOM

EVALUATION OF THE ANTIBACTERIAL ACTIVITY OF Crotalus durissus terrificus CRUDE VENOM

Intradermal Application of Crotamine Induces Inflammatory and Immunological Changes In Vivo

Crotoxin stimulates anM1activation profile in murine macrophages duringLeishmania amazonensisinfection

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