Mechanism of Rhinella icterica (Spix, 1824) toad poisoning using in vitro neurobiological preparations

Oliveira, Raquel Soares; Leal, Allan Pinto; Ogata, Bárbara A.B.; Almeida, Carlos Gabriel Moreira de; Santos, Douglas Silva dos; Lorentz, Leandro Homrich; Moreira, Carlos Heitor Cunha; Bordon, Karla de Castro Figueiredo; Arantes, Eliane Candiani; Santos, Tiágo Gomes dos; Belo, Cháriston André Dal; Vinadé, Lúcia

doi:10.1016/j.neuro.2017.11.006

Cited by 6 publications

(8 citation statements)

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“…In previous work, we examined the effects of RIPS in insect neurological and neuromuscular preparations [27,39] and in rat cardiac tissue [39]. As a continuation of these investigations, in this study we investigated the activity of RIPS and some of its chromatographic fractions in avian central and peripheral nervous tissue and undertook chemical screening to identify the main compounds associated with the pharmacological activity of RIPS.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that RIPS can partially prevent excitotoxicity in mouse brain slices [39]. To confirm this anti-neurotoxic potential, chick brain slices were incubated with RIPS (5, 10, 20, and 40 µg/mL) and its four fractions (RI18, RI19, RI23, and RI24; 5 µg/mL each).…”

Section: Cell Viability In the Presence Of Rips And Its Fractionsmentioning

confidence: 96%

“…All chemicals and reagents used were of the highest purity and were obtained from Sigma-Aldrich (St. Louis, MO, USA), Merck (Rio de Janeiro, RJ, Brazil), or BioRad Laboratories (Hercules, CA, USA). The parotoid secretion was collected as previously described [39] using toads captured near the city of Derrubadas, in the southern Brazilian state of Rio Grande do Sul. The toad capture and secretion collection were authorized by the System of Authorization and Information in Biodiversity (SISBIO, permit n o .…”

Section: Reagents and Secretion Collectionmentioning

confidence: 99%

“…Rhinella icterica parotoid secretion (RIPS) has antimicrobial activity against Escherichia coli and Staphylococcus aureus [38]. In a previous report, we showed that RIPS was toxic to the peripheral and central nervous systems of avian, mammalian, and insect species through a digitalis-like action [27,39]. Although preliminary studies of RIPS have identified some chemical components, such as dehydrobufotenine, hellebrigenin, telocinobufagin, marinobufagin, bufotalin, bufalin, and 19-oxo-cinobufagin [13,36,39], no previous study has sought to examine the chemical constitution of this secretion in detail and to assess its specific interaction with the avian nervous system.…”

Section: Introductionmentioning

confidence: 99%

“…In a previous report, we showed that RIPS was toxic to the peripheral and central nervous systems of avian, mammalian, and insect species through a digitalis-like action [ 27 , 39 ]. Although preliminary studies of RIPS have identified some chemical components, such as dehydrobufotenine, hellebrigenin, telocinobufagin, marinobufagin, bufotalin, bufalin, and 19-oxo-cinobufagin [ 13 , 36 , 39 ], no previous study has sought to examine the chemical constitution of this secretion in detail and to assess its specific interaction with the avian nervous system. In this work, we investigated the chemical composition of RIPS to identify the main groups of compounds responsible for the acute neurotoxicity caused by this secretion at avian skeletal neuromuscular junctions.…”

Section: Introductionmentioning

confidence: 99%

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Chemical and Pharmacological Screening of Rhinella icterica (Spix 1824) Toad Parotoid Secretion in Avian Preparations

Oliveira

Borges

Leal

et al. 2020

Toxins

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The biological activity of Rhinella icterica parotoid secretion (RIPS) and some of its chromatographic fractions (RI18, RI19, RI23, and RI24) was evaluated in the current study. Mass spectrometry of these fractions indicated the presence of sarmentogenin, argentinogenin, (5β,12β)-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide, marinobufagin, bufogenin B, 11α,19-dihydroxy-telocinobufagin, bufotalin, monohydroxylbufotalin, 19-oxo-cinobufagin, 3α,12β,25,26-tetrahydroxy-7-oxo-5β-cholestane-26-O-sulfate, and cinobufagin-3-hemisuberate that were identified as alkaloid and steroid compounds, in addition to marinoic acid and N-methyl-5-hydroxy-tryptamine. In chick brain slices, all fractions caused a slight decrease in cell viability, as also seen with the highest concentration of RIPS tested. In chick biventer cervicis neuromuscular preparations, RIPS and all four fractions significantly inhibited junctional acetylcholinesterase (AChE) activity. In this preparation, only fraction RI23 completely mimicked the pharmacological profile of RIPS, which included a transient facilitation in the amplitude of muscle twitches followed by progressive and complete neuromuscular blockade. Mass spectrometric analysis showed that RI23 consisted predominantly of bufogenins, a class of steroidal compounds known for their cardiotonic activity mediated by a digoxin- or ouabain-like action and the blockade of voltage-dependent L-type calcium channels. These findings indicate that the pharmacological activities of RI23 (and RIPS) are probably mediated by: (1) inhibition of AChE activity that increases the junctional content of Ach; (2) inhibition of neuronal Na+/K+-ATPase, leading to facilitation followed by neuromuscular blockade; and (3) blockade of voltage-dependent Ca2+ channels, leading to stabilization of the motor endplate membrane.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Viability In the Presence Of Rips And Its Fractionsmentioning

confidence: 96%

Section: Reagents and Secretion Collectionmentioning

confidence: 99%