A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Garcia, Juliana; Costa, Vera Marisa; Carvalho, Alexandra; Silvestre, Ricardo; Duarte, José Alberto; Dourado, Daniel F. A. R.; Arbo, Marcelo Dutra; Baltazar, Teresa; Dinis-Oliveira, Ricardo Jorge; Baptista, Paula; Bastos, Maria de Lourdes; Carvalho, Félix

doi:10.1007/s00204-015-1582-x

Cited by 50 publications

(39 citation statements)

References 48 publications

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“…A recent publication has shown that polymyxin B has partially prevented the amanitin-induced toxicity when a lethal dose of αamanitin was used in CD-1 mice. As polymyxin B showed in silico and in vivo to avoid RNA polymerase II inactivation (Garcia et al, 2015d), this recent finding further support the new paradigm of antidotal route for Amanita phalloides poisoning focusing on RNA polymerase II.…”

Section: Treatment and Management Of Intoxications By Amatoxinssupporting

confidence: 57%

Amanita phalloides poisoning: Mechanisms of toxicity and treatment

Garcia

Costa

Carvalho

et al. 2015

Food and Chemical Toxicology

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171

121

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Amanita phalloides, also known as 'death cap', is one of the most poisonous mushrooms, being involved in the majority of human fatal cases of mushroom poisoning worldwide. This species contains three main groups of toxins: amatoxins, phallotoxins, and virotoxins. From these, amatoxins, especially α-amanitin, are the main responsible for the toxic effects in humans. It is recognized that α-amanitin inhibits RNA polymerase II, causing protein deficit and ultimately cell death, although other mechanisms are thought to be involved. The liver is the main target organ of toxicity, but other organs are also affected, especially the kidneys. Intoxication symptoms usually appear after a latent period and may include gastrointestinal disorders followed by jaundice, seizures, and coma, culminating in death. Therapy consists in supportive measures, gastric decontamination, drug therapy and, ultimately, liver transplantation if clinical condition worsens. The discovery of an effective antidote is still a major unsolved issue. The present paper examines the clinical toxicology of A. phalloides, providing the currently available information on the mechanisms of toxicityinvolved and on the current knowledge on the treatment prescribed against this type of mushrooms. Antidotal perspectives will be raised as to set the pace to new and improved therapy against these mushrooms.

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Section: Treatment and Management Of Intoxications By Amatoxinssupporting

confidence: 57%

Amanita phalloides poisoning: Mechanisms of toxicity and treatment

Garcia

Costa

Carvalho

et al. 2015

Food and Chemical Toxicology

Self Cite

171

121

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“…One study performed with the aim of developing an antidotal treatment against α‐AMA in recent years is Garcia et al . experimental research into the use of polymyxin B for therapeutic purposes . That study involved both in silico and in vivo protocols and concluded that polymyxin B prevented α‐AMA‐related organ failure in mice and increased survival rates.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of the Effectiveness of Silibinin and Resveratrol in Preventing Alpha‐Amanitin‐Induced Hepatotoxicity

Şahin

Arıcı

Yılmaz

et al. 2018

Basic Clin Pharma Tox

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Amanita phalloides species mushrooms containing alpha-amanitin (α-AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α-AMA-induced hepatotoxicity. We investigated the effects of resveratrol on α-AMA-induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models. In the in vivo protocol, resveratrol (30 mg/kg) was given simultaneously with α-AMA (α-AMA + SR) or 12 (α-AMA + 12R) or 24 (α-AMA + 24R) hr after α-AMA administration. Silibinin (5 mg/kg) (α-AMA + Sil) and normal saline (α-AMA + NS) were given simultaneously with α-AMA. We found that liver transaminase levels in α-AMA + SR and α-AMA + 12R groups and histomorphologic injury score in the α-AMA + SR, α-AMA + 12R, α-AMA + 24R and α-AMA + Sil groups were significantly lower than that of the α-AMA + NS group. Resveratrol decreased mononuclear cell infiltration, necrosis and active caspase-3 immunopositivity in the liver. In the in vitro protocol, the effects of resveratrol and silibinin were evaluated in a reduction in cell viability induced by α-AMA in THLE-2 and THLE-3 hepatocytes. Neither resveratrol nor silibinin was found to be effective in increasing cell viability decreased by α-AMA + NS. As a conclusion, resveratrol was found to be effective in α-AMA-induced hepatotoxicity with its anti-inflammatory properties in in vivo conditions. It is a promising compound with the potential for use in the treatment of hepatotoxicity associated with Amanita phalloides type mushroom poisonings.

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“…No specific life-saving approach exists. Various pharmacotherapies have been tested including intravenous penicillin G, thioctic acid, N-acetylcysteine, cimetidine, steroids, polymixin B, vitamin C, silymarin, and silibinin (Table 2) [32,34,36,84,[97], [98], [99], [100]]. Thioctic acid, an antioxidant used in cosmetics and anti-aging products due to its ability to scavenge free-radicals, was successfully used to treat amanitin poisoning cases [36], but has been abandoned, being considered inefficient.…”

Section: Toxic Features and Managementmentioning

confidence: 99%