Acute liver failure after amanitin poisoning: a porcine model to detect prognostic markers for liver regeneration

Thiel, Karolin; Schenk, Martin; Sipos, Bence; Sperveslage, Jan; Peter, Andreas; Morgalla, Matthias; Grasshoff, Christian; Königsrainer, Alfred; Thiel, Christian

doi:10.1007/s12072-013-9491-7

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…Apoptosis has been shown to play an important role in α-amanitin-induced liver injury in dog primary hepatocytes and human primary hepatocytes [ 13 , 25 ]. Necrosis was also established in dog hepatocytes and in vivo in the liver of pigs [ 26 , 27 ]. Furthermore, increased cleaved caspase-3 and a concentration-dependent and time-dependent effect were demonstrated in mouse liver Hepa1-6 cells [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…This caused permeabilization of the mitochondrial membrane, release of cytochrome C into the cytosol, and initiation of the intrinsic apoptotic pathway [ 29 ]. Other mechanisms of apoptosis may also be involved, including ROS formation and TNF-α upregulation [ 27 , 28 ]. Our results show that the inhibition of apoptosis prevents a significant amount of α-amanitin-induced toxicity, especially at a high α-amanitin concentration.…”

Section: Discussionmentioning

confidence: 99%

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Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells

Hof,

Visser,

de Jong

et al. 2024

Toxins

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Amanita phalloides poisonings account for the majority of fatal mushroom poisonings. Recently, we identified hematotoxicity as a relevant aspect of Amanita poisonings. In this study, we investigated the effects of the main toxins of Amanita phalloides, α- and β-amanitin, on hematopoietic cell viability in vitro. Hematopoietic cell lines were exposed to α-amanitin or β-amanitin for up to 72 h with or without the pan-caspase inhibitor Z-VAD(OH)-FMK, antidotes N-acetylcysteine, silibinin, and benzylpenicillin, and organic anion-transporting polypeptide 1B3 (OATP1B3) inhibitors rifampicin and cyclosporin. Cell viability was established by trypan blue exclusion, annexin V staining, and a MTS assay. Caspase-3/7 activity was determined with Caspase-Glo assay, and cleaved caspase-3 was quantified by Western analysis. Cell number and colony-forming units were quantified after exposure to α-amanitin in primary CD34+ hematopoietic stem cells. In all cell lines, α-amanitin concentration-dependently decreased viability and mitochondrial activity. β-Amanitin was less toxic, but still significantly reduced viability. α-Amanitin increased caspase-3/7 activity by 2.8-fold and cleaved caspase-3 by 2.3-fold. Z-VAD(OH)-FMK significantly reduced α-amanitin-induced toxicity. In CD34+ stem cells, α-amanitin decreased the number of colonies and cells. The antidotes and OATP1B3 inhibitors did not reverse α-amanitin-induced toxicity. In conclusion, α-amanitin induces apoptosis in hematopoietic cells via a caspase-dependent mechanism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells

Hof,

Visser,

de Jong

et al. 2024

Toxins

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“…1 Among the amatoxins, the amanitins (α,β,γ) have been evaluated for their toxicity in several animals studies. [2][3][4][5][6][7] The primary mechanism of action of the toxins involves irreversible inhibition of RNA polymerase II. Termination of transcription causes decreased protein synthesis and ultimately cellular necrosis, particularly in cell types with high metabolic rates such as hepatocytes, intestinal crypt cells, and renal tubular epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Amatoxins refer to the group of bicyclic octapeptides produced by mushrooms of the genera Amanita , Galerina , and Lepiota 1 . Among the amatoxins, the amanitins (α,β,γ) have been evaluated for their toxicity in several animals studies 2–7 . The primary mechanism of action of the toxins involves irreversible inhibition of RNA polymerase II.…”

Section: Discussionmentioning

confidence: 99%

Clinical recovery of 5 dogs from amatoxin mushroom poisoning using an adapted Santa Cruz protocol for people

Goupil¹,

Davis

Kaufman³

et al. 2021

J Vet Emergen Crit Care

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Objective: To describe the clinical course, treatment, and outcome of 5 dogs following ingestion of toxic Amanita spp. mushrooms containing amatoxins using an adapted version of the Santa Cruz protocol developed for people.Case series summary: Five dogs were presented with clinical signs compatible with amanitin toxicity with witnessed ingestion noted in 3 of 5 dogs. Clinical findings included acute onset vomiting and diarrhea, lethargy, and hepatopathy including signs of fulminant hepatic failure (increased liver enzyme activities, hyperbilirubinemia, prolonged clotting times, and hypoglycemia were noted among these cases). Urine toxicological screening confirmed the presence of Amanita toxins in 4 cases with expert mycologist speciation in the fifth. Core interventions included percutaneous biliary drainage, use of octreotide, and early nil per os orders. All dogs survived to discharge with this treatment strategy.New or unique information provided: This case series describes the use of a modified version of the Santa Cruz protocol to address amatoxin-induced fulminant hepatic failure in dogs. The protocol was safe, well tolerated, and all patients made a full clinical recovery. K E Y W O R D Sacute kidney injury, Amanita toxins, canine, hepatic failure INTRODUCTIONMushrooms containing amatoxins can cause significant morbidity and mortality when ingested. A novel protocol under clinical trial investigation in people (the Santa Cruz protocol) aims to minimize the need for liver transplantation by combining aggressive diuresis, octreotide, nil per os (NPO) orders, and an IV preparation of silibinin for hepatic pro-

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“…Approximately 400 of these are toxic to humans. Over 90% of fatal mushroom poisonings in the world occur after ingestion of Amanita species [ 8 – 10 ]. There are two distinct groups of toxins isolated from Amanita : phallotoxins and amatoxins.…”

Section: Discussionmentioning

confidence: 99%

Timing of liver transplantation for pediatric acute liver failure due to mushroom poisoning: a case report and literature review

Yang

Sheng

et al. 2020

BMC Pediatr

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Background: Pediatric acute liver failure is a rare, life-threatening illness. Mushroom poisoning is a rare etiology. For patients with irreversible pediatric acute liver failure, liver transplantation is the ultimate lifesaving therapy. However, it is difficult to determine the optimal timing of transplantation. Here, we present a case of pediatric acute liver failure due to mushroom poisoning in northeastern China. He was treated with liver transplantation and recovered. To our knowledge, there are few reports about liver transplantation for pediatric acute liver failure caused by mushroom poisoning in mainland China. Case presentation: The patient was a previously healthy 9-year-old boy who gradually developed nausea, vomiting, jaundice and coma within 5 days after ingesting mushrooms. He was diagnosed with mushroom poisoning and acute liver failure. He was treated with conservative care but still deteriorated. On the 7th day after poisoning, he underwent LT due to grade IV hepatic encephalopathy. Twenty days later, he recovered and was discharged. A review of the literature revealed that the specific criteria and optimal timing of transplantation remain to be determined. Conclusions: Patients with pediatric acute liver failure should be transferred to a center with a transplant unit early. Once conservative treatment fails, liver transplantation should be performed.

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Acute liver failure after amanitin poisoning: a porcine model to detect prognostic markers for liver regeneration

Cited by 6 publications

References 24 publications

Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells

Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells

Clinical recovery of 5 dogs from amatoxin mushroom poisoning using an adapted Santa Cruz protocol for people

Timing of liver transplantation for pediatric acute liver failure due to mushroom poisoning: a case report and literature review

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