Proteins from the Rhinella schneideri parotoid gland secretion exhibit anti-nociceptive effect against nociception induced by inflammation

Freitas, Cléverson D.T.; Sousa-Filho, Luis M.; Lima, Mauro Sérgio Cruz Souza; Pereira, Anna C. T. C.; Ferreira, Gustavo Portela; Lopes, Francisco E.S.; Silva, Renan Oliveira; Barbosa, André Luiz dos Reis; Oliveira, Jefferson Soares de

doi:10.1016/j.biopha.2017.06.104

Cited by 4 publications

(3 citation statements)

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“…Although toads are widely spread in Brazilian and Latin America territory, its cutaneous peptides and proteins have come to the spotlight only recently and the scarce information hinders its assessment [ 11 , 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Rhinella schneideri parotoid gland poison has shown activity against different human cancer cells proliferation [ 13 ], activate human complement system [ 14 ] and inhibit chymotrypsin [ 15 ]. Protein components present anti-inflammatory, anti-nociceptive and toxic activities in mice [ 16 ] Similarly, protein from Bufo bufo parotoid secretions are likely to play a role in cardiotoxic effects [ 17 ] and B. bufo, B. verrucosissimus and Bufotes variabilis both parotoid and skin secretion protein are capable of inhibiting different gram-negative bacteria and cytotoxic effects on different types of cells [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Deep sequencing analysis of toad Rhinella schneideri skin glands and partial biochemical characterization of its cutaneous secretion

Shibao

Cologna

Filho

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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BackgroundAnimal poisons and venoms are sources of biomolecules naturally selected. Rhinella schneideri toads are widespread in the whole Brazilian territory and they have poison glands and mucous gland. Recently, protein from toads’ secretion has gaining attention. Frog skin is widely known to present great number of host defense peptides and we hypothesize toads present them as well. In this study, we used a RNA-seq analysis from R. schneideri skin and biochemical tests with the gland secretion to unravel its protein molecules.MethodsTotal RNA from the toad skin was extracted using TRizol reagent, sequenced in duplicate using Illumina Hiseq2500 in paired end analysis. The raw reads were trimmed and de novo assembled using Trinity. The resulting sequences were submitted to functional annotation against non-redundant NCBI database and Database of Anuran Defense Peptide. Furthermore, we performed caseinolytic activity test to assess the presence of serine and metalloproteases in skin secretion and it was fractionated by fast liquid protein chromatography using a reverse-phase column. The fractions were partially sequenced by Edman’s degradation.ResultsWe were able to identify several classes of antimicrobial peptides, such as buforins, peroniins and brevinins, as well as PLA2, lectins and galectins, combining protein sequencing and RNA-seq analysis for the first time. In addition, we could isolate a PLA2 from the skin secretion and infer the presence of serine proteases in cutaneous secretion.ConclusionsWe identified novel toxins and proteins from R. schneideri mucous glands. Besides, this is a pioneer study that presented the in depth characterization of protein molecules richness from this toad secretion. The results obtained herein showed evidence of novel AMP and enzymes that need to be further explored.Electronic supplementary materialThe online version of this article (10.1186/s40409-018-0173-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deep sequencing analysis of toad Rhinella schneideri skin glands and partial biochemical characterization of its cutaneous secretion

Shibao

Cologna

Filho

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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“…In recent years, several biological properties have been characterized from Rhinella schneideri 'Schneider's toad' poison (Rostelato-Ferreira et al, 2011;Rostelato-Ferreira et al, 2014;Abdelfatah, Lu, Schmeda-Hirschmann, & Efferth, 2019;Leal et al, 2020), a species widely distributed in Brazil (Wake, 2020), including the chemical identification and structural characterization of bufadienolides, e.g., marinobufagenin, bufalin, telocinobufagin, hellebrigenin, 20S21R-epoxymarinobufagin and β-sitosterol, which exhibit cytotoxic activity, modulatory action on the complement cascade, anti-inflammatory activity, inhibitory action of serine protease, presynaptic neuromuscular blocking activity and anticonvulsant action (Cunha-Filho et al, 2010;Anjolette et al, 2015;Sousa-Filho et al, 2016;Shibao, Anjolette, Lopes, & Arantes, 2015;Freitas et al, 2017;Rostelato-Ferreira et al, 2018;Baldo et al, 2019;Zheng et al, 2020).…”

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confidence: 99%

Action of heparin and acetylcholine modulators on the neurotoxicity of the toad Rhinella schneideri (Anura: Bufonidae) in Brazil

et al. 2021

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Introduction: Rhinella schneideri is a toad widely distributed in South America and its poison is characterized by inducing cardiotoxicity and neurotoxicity. Objective: In this work, we investigated pharmacological strategies to attenuate the peripheral neurotoxicity induced by R. schneideri poison in avian neuromuscular preparation. Methods: The experiments were carried out using isolated chick biventer cervicis preparation subjected to field stimulation for muscle twitches recordings or exposed to acetylcholine and potassium chloride for contracture responses. Results: Poison (10 μg/ml) produced complete neuromuscular blockade in chick biventer cervicis preparation within approximately 70 min incubation (times for 50 and 90 % blockade: 15 ± 3 min and 40 ± 2 min, respectively; P < 0.05, N= 5); contracture responses to exogenous acetylcholine and KCl were unaffected by poison indicating no specificity with postsynaptic receptors or myotoxicity, respectively. Poison (10 μg/ml)-induced neuromuscular blockade was not prevented by heparin (5 and 150 IU/ml) under pre- or post-treatment conditions. Incubation at low temperature (23-25 °C) abolished the neuromuscular blockade; after raising the temperature to 37 °C, the complete neuromuscular blockade was slightly slower than that seen in preparations directly incubated at 37 °C (times for 50 and 90 % blockade: 23 ± 2 min and 60 ± 2.5 min, respectively; P < 0.05, N= 4). Neostigmine (3.3 μM) did not reverse the neuromuscular blockade in BC preparation whereas 3,4-diaminopyridine (91.6 μM) produced a partial and sustained reversal of the twitch responses (29 ± 7.8 % of maximal reversal reached in approximately 40 min incubation; P < 0.05, N= 4). Conclusions: R. schneideri poison induces potent peripheral neurotoxicity in vitro which can be partially reversible by 3,4-diaminopyridine.

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Esc‐1GN shows therapeutic potentials for acne vulgaris and inflammatory pain

Xu³

et al. 2020

Journal of Peptide Science

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The inflammatory response plays important roles in acne vulgaris and pain pathogenesis. In previous study, Esc‐1GN with anti‐inflammatory, antimicrobial, and lipopolysacchride (LPS) binding activity was identified from the skin of the frog Hylarana guentheri. Here, we report its therapeutic potentials for acne vulgaris and inflammatory pain. Esc‐1GN destroyed the cell membrane of Propionibacteria acnes in the membrane permeability assays. In addition, bacterial agglutination test suggested that Esc‐1GN triggered the agglutination of P. acnes, which was affected by LPS and Ca2+. Meanwhile, in vivo anti‐P. acnes and anti‐inflammatory effects of Esc‐1GN were confirmed by reducing the counts of P. acnes in mice ear, relieving P. acnes‐induced mice ear swelling, decreasing mRNA expression and the production of pro‐inflammatory cytokines, and attenuating the infiltration of inflammatory cells. Moreover, Esc‐1GN also displayed antinociceptive effect in mice induced by acetic acid and formalin. Therefore, Esc‐1GN is a promising candidate drug for treatment of acne vulgaris and inflammatory pain.

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Proteins from the Rhinella schneideri parotoid gland secretion exhibit anti-nociceptive effect against nociception induced by inflammation

Cited by 4 publications

References 19 publications

Deep sequencing analysis of toad Rhinella schneideri skin glands and partial biochemical characterization of its cutaneous secretion

Deep sequencing analysis of toad Rhinella schneideri skin glands and partial biochemical characterization of its cutaneous secretion

Action of heparin and acetylcholine modulators on the neurotoxicity of the toad Rhinella schneideri (Anura: Bufonidae) in Brazil

Esc‐1GN shows therapeutic potentials for acne vulgaris and inflammatory pain

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