An outbreak of Galerina sulciceps-like (Galerina cf. sulciceps) mushroom poisoning.

OBJECTIVE: Amatoxin-containing mushroom poisoning is a significant threat to public health worldwide. We report a mass poisoning of Galerina sulciceps-like mushrooms (Galerina cf. sulciceps) in Luzhou, Sichuan Province, China, aiming to offer insights for future prevention and treatment strategies. METHODS: We performed a retrospective survey of mass mushroom poisoning patients admitted to our hospital. The demographic data, clinical presentations, laboratory findings, therapeutic measures and prognostic information were collected and analyzed. We used the 2020 Chinese consensus on the clinical diagnosis and treatment of amatoxin-containing mushroom poisoning to assess the severity of poisoning. Mushrooms were examined through morphological analysis, molecular biology identification, and toxin detection. RESULTS: Our patient cohort consisted of nine males and six females, with mean (±SD) age of 34.9 ± 13.0 years. Gastrointestinal symptoms were the first to manifest, with mean (±SD) latency period of 13.4 ± 3.9 h. The majority of patients (86.7%) experienced nausea, vomiting, and diarrhea. Liver dysfunction was noted in 66.7% of patients, and thrombocytopenia was present in 26.7% of patients. In terms of the severity of poisoning, there were 10 mild cases and 5 severe cases. The mushrooms were provisionally labeled as Galerina cf. sulciceps, containing the toxins α-amanitin, ß-amanitin, and γ-amanitin. All patients eventually recovered. DISCUSSION: We report what appears to be a new type of mushroom that is morphologically and phylogenetically similar to the known Galerina sulciceps, but further study is required to determine if it represents a distinct species. CONCLUSION: This poisoning event was caused by unintentional ingestion of Galerina cf. sulciceps, an amatoxin-containing mushroom. Early symptoms are primarily gastrointestinal, with acute liver damage and coagulopathy being the main toxic effects. Thrombocytopenia is also prominent, particularly in severe cases. Accurate assessment and prompt, individualized, and intensive treatment are crucial for managing patients with acute Galerina cf. sulciceps poisoning effectively.

Effects of interrupting the enterohepatic circulation in amatoxin intoxications.

BACKGROUND: Interruption of the enterohepatic circulation is regarded as an effective way to treat patients with amatoxin poisoning. Nonetheless, its effectiveness has not yet been systematically evaluated. Therefore, we performed a systematic review to investigate the role of enterohepatic circulation on patient outcome and clinical laboratory values. We specifically sought to evaluate the effect of activated charcoal, which absorbs drugs and toxins in the gastrointestinal tract. METHODS: A previously established database with data extracted from case reports and series from literature, supplemented with recent publications, was used. Patient characteristics, outcome, and laboratory values were evaluated. RESULTS: We included 133 publications describing a total of 1,119 unique cases. Survival was 75 per cent in the control group (n = 452), whereas in the group treated with single or multiple doses of activated charcoal (n = 667) survival was 83 per cent (P < 0.001, odds ratio 1.89 [95 per cent confidence interval 1.40-2.56]). Furthermore, no difference in peak values of alanine aminotransferase and aspartate aminotransferase activities were observed, whereas peak values of total serum bilirubin concentration and international normalized ratio were statistically significantly reduced in patients treated with activated charcoal. DISCUSSION: The ability of activated charcoal to enhance the elimination of amatoxin through interruption of the enterohepatic circulation offers a potentially safe and inexpensive therapy for patients in the post-absorptive phase. LIMITATIONS: Limitations include the potential for publication bias, the lack of universal confirmation of amatoxin concentrations, and the inability to directly measure enterohepatic circulation of amatoxin. CONCLUSION: Treatment with activated charcoal in patients with amatoxin poisoning was associated with a greater chance of a successful outcome. Additionally, activated charcoal was associated with a reduction in markers of liver function, but not markers of liver injury.

Ganoderic acid A attenuated hepatic impairment by down-regulating the intracellular JAK2-STAT3 signaling pathway in induced mushroom poisoning.

BACKGROUND: Mushroom poisoning is one of the most prominent public health problems. However, there is no special antidote so far. In the present study, we verified that Ganoderma lucidum may be an effective approach for treatment of acute mushroom poisoning. METHODS: A retrospective study was performed within the past 20 years, we compiled information on the treatment of α-Amatoxin mushroom poisoning with Ganoderma lucidum by evaluating the mortality rate and liver function before and after treatment. Moreover, we explore the potential underlying mechanism of Ganoderma lucidum in the treatment of α-amanita poisoning in both in vivo animal experiments and in vitro cell experiments. RESULTS: In our study, a total of 556 cases of mushroom poisoning were integrated over the past 20 years, the primary outcome was in-hospital mortality. Specificity, descriptive data of ALT, AST, BA and STB were evaluated for the effectiveness of protection to acute liver damage. From 1994 to 2002, there were 55 cases of mushroom poisoning in which 372 individuals were poisoned, 129 individuals died, with a mortality of 35%. Since 2002, after being treated with Ganoderma lucidum, surprisingly, the mortality decreased to 0%, and all the 184 patients were cured, the hepatic impairment improved significantly within 10 days. Based on a multivariate logistic regression analyses, after adjusting for age, gender and baseline clinical indicators, it was found that Ganoderma lucidum treatment was effective in reducing the morbidity (OR = 0.58), and Ganoderma lucidum treatment also showed an improvement in liver enzymes and in shortening the length of hospitalization significantly. Meanwhile, the main components of Ganoderma lucidum, Ganoderic acid A could significantly improve the survival rate and liver function in α-Amatoxin poisoned mice and may effectively inhibit the JAK2-STAT3 pathway, which could contribute to the detoxification in poisoned patients. CONCLUSION: Ganoderma lucidum is very effective in treating mushroom poisoning by α-amanita and is worth promoting.

Wild mushroom poisoning: A case study of amatoxin-containing mushrooms and implications for public health.

Wild mushroom poisoning is a global public health concern, with mushrooms containing amatoxins being the main cause of fatalities. Mushrooms from the genus Amanita and Galerina contain amatoxins. Here we present a case of wild mushroom poisoning that affected three individuals, resulting in two fatalities. Within 10-15 hours after consumption, they experienced symptoms of gastroenteritis such as vomiting, abdominal pain, and diarrhea. One individual sought medical attention promptly and recovered, while the other two sought medical help nearly two or three days after the onset of symptoms, by which time their conditions had already worsened and led to their deaths. The mushrooms were identified belonging to genus Galerina, and laboratory test revealed variations in toxin levels among mushrooms collected from different parts of the decaying stump. The higher levels of α-amanitin, ß-amanitin, and γ-amanitin were detected near the base of the tree stump, but trace levels of α-amanitin were found near the top of the stump, while ß-amanitin and γ-amanitin were undetectable. This case emphasizes the importance of seeking immediate medical attention when experiencing delayed-onset gastrointestinal symptoms, as it may indicate more severe mushroom poisoning, particularly amatoxin poisoning. Timely and appropriate treatment is equally important. Additionally, consuming different units of the mushrooms in the same incident can lead to varying prognoses due to differences in toxin levels.

Amanita Mushroom Toxin Poisoning in Los Angeles County.

Mushroom (amatoxin) poisoning from ingestion is a rare but life-threatening medical emergency characterized by gastrointestinal symptoms before progression to multisystem organ failure in severe cases. Many therapies of amatoxin intoxication have been described, including supportive care, medical therapies, detoxification strategies, and liver transplant. The evidence supporting these therapies remains limited due to the rarity of amatoxin poisoning and challenge of a timely diagnosis. We report a case of amatoxin poisoning in Los Angeles causing severe liver injury without acute liver failure treated successfully using medical therapies, gallbladder drainage, and plasma exchange.

A ten-year retrospective California Poison Control System experience with possible amatoxin mushroom calls.

INTRODUCTION: Mushrooms containing amatoxin are found worldwide and represent a challenging poisoning for the clinician and consulting poison center. This study evaluates the experience of a large poison system with possible amatoxin-containing mushroom ingestion calls. METHODS: A 10-year retrospective review of the California Poison Control System database was performed for amatoxin mushroom ingestion calls resulting in hospitalization. Cases found were abstracted and data statistically analyzed for association with a composite endpoint of death, liver transplant, and/or the need for dialysis. RESULTS: Amatoxin-containing mushroom calls are infrequent with the vast majority (98.4 percent) coming from Northern California during the rainier first and fourth quarters (October through March) of the year. Elevated initial aminotransferase activities and international normalized ratios were predictive of the composite negative outcome. The mortality plus liver transplant and hemodialysis composite rate was 8.2 percent, consistent with current literature. CONCLUSION: The California Poison Control System has relatively few amatoxin-containing mushroom ingestion calls that result in hospitalization but those that are reported mostly occur in Northern California. Treatment bias towards the sickest patients may explain the association of intravenous fluid use or treatment with acetylcysteine or silibinin with meeting the composite outcome. The initial presence of elevated hepatic aminotransferase activity and international normalized ratios are poor prognostic indicators and are likely reflective of late presentation, an advanced toxic phase of amatoxin poisoning, and/or delays in time to obtain poison center consultation.

[Amatoxin-containing mushroom poisoning: An update]. / Syndrome phalloïdien : mise au point.

Amatoxin-containing mushroom poisoning occurs after consumption of certain mushroom species, of the genera Amanita, Lepiota and Galerina. Amanita phalloides is the most implicated species, responsible for over more than 90% of mushroom-related deaths. The α-amanitin is responsible for most of the observed effects. Symptoms are characterized by severe delayed gastrointestinal disorders (more than six hours after ingestion). The liver being the main target organ, outcome is marked by an often severe hepatitis which can evolve towards terminal liver failure, justifying orthotopic liver transplantation. Acute renal failure is common. Diagnosis of amatoxin-containing mushroom poisoning is based primarily on clinical data; it can be biologically confirmed using detection of amatoxins, especially from urine samples. In the absence of an antidote, early hospital management is essential. It is based on supportive care (early compensation of hydroelectrolytic losses), gastrointestinal digestive decontamination, elimination enhancement, amatoxin uptake inhibitors and antioxidant therapy. Combined therapy associating silibinin and N-acetylcysteine is recommended. Prognosis of this severe poisoning has greatly benefited from improved resuscitation techniques. Mortality is currently less than 10%. In the event of a suspected or confirmed case, referral to a Poison Control Center is warranted in order to establish the diagnosis and guide the medical management of patients in an early and appropriate way.

Hypoadrenocorticism in a Dog Following Recovery from Alpha-Amanitin Intoxication.

A 10-year-old, female spayed Labrador Retriever was referred for acute hepatopathy and urinary retention. Blood work from the initial presentation (day 0) revealed a severe, mixed hepatopathy. Over the course of the patient's hospitalization, the patient developed liver insufficiency. Urine was submitted for toxicological screening and revealed detection of a trace concentration of alpha-amanitin. The patient was treated supportively for alpha-amanitin intoxication and was discharged from the hospital on day 8, with most biochemical parameters being markedly improved. The patient was persistently hyporexic at the time of discharge. On day 15, at a recheck appointment, the patient had lost 2.4 kg and liver enzymology revealed improved values. On day 24, the patient was presented for anorexia and vomiting and had lost another 2.3 kg. Blood work and endocrinological testing at that time were consistent with hypoadrenocorticism. The patient was started on glucocorticoids and mineralocorticoids. At day 106, the patient was doing well clinically while receiving monthly mineralocorticoids and daily glucocorticoids. This case report is the first to describe the chronological association between alpha-amanitin-induced liver dysfunction and the subsequent development of adrenal insufficiency in a dog.

Amatoxin poisoning caused by Galerina sulciceps, a species with no prior record of identification in Japan: a case report.

A 60-year-old man presented with acute gastroenteritis, hypovolemic shock, acute renal failure (BUN/Cr, 56.7/4.24 mg/dl), and aspiration pneumonia. The previous day, he ingested 30 caps of mushrooms of an unknown species. The patient was treated with a massive intravenous infusion, renal replacement therapy, and antimicrobial agents. Late-onset mild liver injury peaked on day 11 (AST/ALT, 62/67 IU/l). Acute renal failure improved once before worsening, with the worst symptoms on day 19 (BUN/Cr, 99/6.61 mg/dl). Thereafter, the patient showed gradual improvement, and renal replacement therapy was discontinued on day 23. His general condition improved fully and he was transferred to another hospital for rehabilitation on day 47. The mushrooms were later identified as Galerina sulciceps by the Basic Local Alignment Search Tool, and toxicologic analysis using liquid chromatography-tandem mass spectrometry revealed an average of 85 ppm α-amanitin and 330 ppm ß-amanitin in the tissue of the mushrooms brought in by the patient's family. Galerina sulciceps is distributed mainly in tropical and subtropical regions of Southeast Asia and had never been identified before in Japan. The heat of fermentation generated by the thick layer of wood chips on the ground or global warming may have contributed to its growth in Japan. Interestingly, our patient did not have liver dysfunction, which is one main and typical amatoxin poisoning symptom. Variation in clinical presentation may be attributed to the different ratios of α-amanitin to ß-amanitin in different mushroom species.

An outbreak of Amanita exitialis poisoning.

BACKGROUND: The mushroom Amanita exitialis is reported to cause acute liver injury. It is found in Southern China, and has been previously associated with a high incidence of mortality. METHODS: We described a series of 10 patients with Amanita exitialis poisoning admitted to The Second Affiliated Hospital of the Chinese University of Hong Kong (Shenzhen) in April 2022. Patient demographics, clinical features, laboratory results, therapeutic interventions, and outcome data were collected. RESULTS: Among the 10 patients, 9 survived, while 1 died. Gastrointestinal symptoms were the first to appear (average latency period, 11 ± 4.2 h). Diarrhea was the most common clinical symptom (average duration, 4.4 days). Abdominal distention was an important sign, especially in severely-ill patients. Thrombocytopenia occurred on day 2 after mushroom ingestion and persisted for 3-4 days. Alanine aminotransferase and total bilirubin peaked on days 2-3. CONCLUSION: Amanita exitialis poisoning is characterized by gastrointestinal symptoms and liver injury. In the patient who died, acute hepatic failure led to hepatic encephalopathy and cerebral edema. Abdominal distension accompanied by thrombocytopenia was common in critically ill patients in this outbreak.

Target recognition assisted-primer exchange reaction (Ta-PER) for sensitive analysis of p53 gene and its application in analyzing amatoxin-treated samples.

Sensitive and reliable detection of the p53 gene plays a significant role in precise cancer targeting and in fundamental research. However, the sensitivity of existing p53 gene detection approaches remains to be improved. Herein, we develop a target recognition assisted-primer exchange reaction (Ta-PER) for sensitive analysis of the p53 gene. Ta-PER was initiated by the recognition of a designed dumbbell structure probe by the p53 gene. In Ta-PER, the primer exchange reaction (PER) was combined with molecular beacon-based chain recycling to construct the signal amplification process. Through integrating target recognition with PER-based signal amplification, Ta-PER was established and exhibited a high detection sensitivity, with a limit of detection as low as 56 fM. In addition, the approach was also used to detect the p53 gene in normal HeLa cells and amatoxin-treated HeLa cells. The high level of the p53 gene in amatoxin-treated HeLa cells, which was approximately 1.67 times higher than that in HeLa cell extract, indicated the apoptosis of cells and suggested the promising prospect of the approach.

Mushroom Poisoning: A Rare Etiology of Acute Liver Failure.

Acute liver failure is defined as a rapid deterioration in liver function, manifested by symptoms and signs of hepatic encephalopathy and disturbed synthetic function in a patient without Pre-existing cirrhosis and with an illness of less than 26 weeks duration. Mushroom poisoning as a cause of acute liver injury is rare but associated with deadly outcomes if not early recognized and treated. The mortality is very high in the case of amatoxin-containing mushrooms ingestion and liver transplantation is the only lifesaving option. Therefore, early recognition of a suspected patient who came with features of mushroom-related food poisoning, timely referral to a liver transplantation center, and adequate supportive management remain the main approaches of management in a patient with acute liver injury. We present a patient with gastroenteritis who ingested wild mushroom 14 hours prior to hospital admission with subsequent severe acute liver failure due to mushroom poisoning, successfully treated with urgent liver transplantation. This case study highlighted that careful evaluation of the symptoms and signs of acute liver failure in a patient with a history of mushroom ingestion can result in early referral to a liver transplant center, especially if the patient is systemically unwell.

Amanitin intoxication: effects of therapies on clinical outcomes - a review of 40 years of reported cases.

BACKGROUND AND AIMS: Amanita phalloides poisoning causes severe liver damage which may be potentially fatal. Several treatments are available, but their effectiveness has not been systematically evaluated. We performed a systematic review to investigate the effect of the most commonly used therapies: N-acetylcysteine (NAC), benzylpenicillin (PEN), and silibinin (SIL) on patient outcomes. In addition, other factors contributing to patient outcomes are identified. METHODS: We searched MEDLINE and Embase for case series and case reports that described patient outcomes after poisoning with amanitin-containing Amanita mushrooms. We extracted clinical characteristics, treatment details, and outcomes. We used the liver item from the Poisoning Severity Score (PSS) to categorize intoxication severity. RESULTS: We included 131 publications describing a total of 877 unique cases. The overall survival rate of all patients was 84%. Patients receiving only supportive care had a survival rate of 59%. The use of SIL or PEN was associated with a 90% (OR 6.40 [3.14-13.04]) and 89% (OR 5.24 [2.87-9.56]) survival rate, respectively. NAC/SIL combination therapy was associated with 85% survival rate (OR 3.85 [2.04, 7.25]). NAC/PEN/SIL treatment group had a survival rate of 76% (OR 2.11 [1.25, 3.57]). Due to the limited number of cases, the use of NAC alone could not be evaluated. Additional analyses in 'proven cases' (amanitin detected), 'probable cases' (mushroom identified by mycologist), and 'possible cases' (neither amanitin detected nor mushroom identified) showed comparable results, but the results did not reach statistical significance. Transplantation-free survivors had significantly lower peak values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total serum bilirubin (TSB), and international normalized ratio (INR) compared to liver transplantation survivors and patients with fatal outcomes. Higher peak PSS was associated with increased mortality. CONCLUSION: Based on data available, no statistical differences could be observed for the effects of NAC, PEN or SIL in proven poisonings with amanitin-containing mushrooms. However, monotherapy with SIL or PEN and combination therapy with NAC/SIL appear to be associated with higher survival rates compared to supportive care alone. AST, ALT, TSB, and INR values are possible predictors of potentially fatal outcomes.

Mushroom mycetism - A neglected and challenging medical emergency in the Indian subcontinent: A road map for its prevention and treatment.

Edible mushrooms, a class of macroscopic fungi, serve as delicious and nutritious food supplements around the world. Nevertheless, accidental consumption of poisonous mushrooms that results in fatality or severe illness is typical in all countries, especially among the tribal indigenous communities that forage wild mushrooms for food. In the Indian subcontinent, mushroom poisoning cases are underreported and neglected. Different classes of toxins, characterized from the poisonous mushrooms found globally, show variable clinical symptoms post-consumption. Although the Indian subcontinent is a biodiversity hotspot and home to different classes of fungi and mushrooms, many species of poisonous mushrooms and their toxins, have yet to be identified and characterized. No epidemiological studies or retrospective analyses of mushroom poisoning cases have been reported from the poison control centers in the Indian subcontinent. Nevertheless, some limited clinical and epidemiological data is available from India and Nepal, and therefore, we critically analyse the mushroom poisoning scenario in these countries, and discuss the mushroom toxins that are likely responsible for the post-ingestion toxicities. We also correlate the clinical manifestations of mushroom intoxication in India and Nepal with the pharmacological properties of the prevalent mushroom toxins in these countries. Our limited study of mushroom poisoning demonstrates that the adverse pharmacological effects of amatoxin, one of the deadliest mushroom toxins, are responsible for the highest mortality and morbidity in India and Nepal. Further, no specific antidote is available to treat mushroom intoxication in the region, and systemic and supportive care is all that is available for in-patient management of cases of severe poisoning. We also suggest a roadmap for the prevention and specific treatment against mushroom poisoning in the Indian subcontinent.

Smartphone-based paper microfluidic competitive immunoassay for the detection of α-amanitin from mushrooms.

α-Amanitin is often considered the most poisonous mushroom toxin produced by various mushroom species, which are hard to identify from edible, non-toxic mushrooms. Conventional detection methods require expensive and bulky equipment or fail to meet high analytical sensitivity. We developed a smartphone-based fluorescence microscope platform to detect α-amanitin from dry mushroom tissues. Antibody-nanoparticle conjugates were captured by immobilized antigen-hapten conjugates while competing with the free analytes in the sample. Captured fluorescent nanoparticles were excited at 460 nm and imaged at 500 nm. The pixel numbers of such nanoparticles in the test zone were counted, showing a decreasing trend with increasing analyte concentration. The detection method exhibited a low detection limit (1 pg/mL), high specificity, and selectivity, allowing us to utilize a simple rinsing for toxin extraction and avoiding the need for high-speed centrifugation. In addition, this assay's short response time and portable features enable field detection of α-amanitin from amanitin-producing mushrooms.

Delayed liver toxicity and delayed gastroenteritis: A 5 year retrospective analysis of the cause of death in Mushroom poisoning.

Introduction: Mushroom poisoning occurs from consumption of the wild variants of mushroom containing varied forms of toxins. Among those toxins, amatoxin containing mushrooms are known for the significant morbidity and mortality from hepatic toxicity and delayed gastroenteritis. Although not a very common cause of poisoning, it is prevalent in the north-eastern region of India, especially during the rainy summer seasons when the wild variants are found abundantly and often confused with the edible variants. Aims and Objectives: To study the clinical and biochemical profiles and short term outcomes of patients with mushroom poisoning admitted to a tertiary care hospital. Materials and Methods: We analyzed the data of patients with mushroom poisoning admitted to a tertiary care institute in north-eastern India between January 2015 to December 2020 to study their clinical and biochemical profiles, and short-term outcomes. Their clinical features, biochemical parameters, management, and in-hospital outcomes were noted. All data was recorded in Microsoft MS Excel and analyses done using SPSS version 22. Results: Of the 44 patients with mushroom poisoning, 23 (52%) were male and 21 (47%) were female, with a mean age of 20.13 years. Seventeen patients (38%) had delayed liver failure and delayed gastroenteritis, 19 patients (43%) had acute gastroenteritis syndrome, 5 patients (11%) had cholinergic symptoms, one patient (2%) each had acute kidney injury and a disulfiram-type reaction with headache. The mean hospital stay of the patients was 5 days. In-hospital mortality occurred in 10 (58%) patients with delayed liver failure and none of the patients with the other complications died. Conclusion: This study revealed a high prevalence of mushroom poisoning that caused delayed liver toxicity and delayed gastroenteritis, probably amatoxin-induced, which is fatal, thus accounting for high mortality and poor outcomes in these patients.

Design, Synthesis, and Biochemical Evaluation of Alpha-Amanitin Derivatives Containing Analogs of the trans-Hydroxyproline Residue for Potential Use in Antibody-Drug Conjugates.

Alpha-amanitin, an extremely toxic bicyclic octapeptide extracted from the death-cap mushroom, Amanita phalloides, is a highly selective allosteric inhibitor of RNA polymerase II. Following on growing interest in using this toxin as a payload in antibody-drug conjugates, herein we report the synthesis and biochemical evaluation of several new derivatives of this toxin to probe the role of the trans-hydroxyproline (Hyp), which is known to be critical for toxicity. This structure activity relationship (SAR) study represents the first of its kind to use various Hyp-analogs to alter the conformational and H-bonding properties of Hyp in amanitin.

In vivo and in vitro α-amanitin metabolism studies using molecular networking.

Amanitin poisonings are among the most life-threatening mushroom poisonings, and are mainly caused by the genus Amanita. Hepatotoxicity is the hallmark of amanitins, powerful toxins contained in these mushrooms, and can require liver transplant. Among amatoxins, α-amanitin is the most studied. However, the hypothesis of a possible metabolism of amanitins is still controversial in this pathophysiology. Therefore, there is a need of clarification using cutting-edge tools allowing metabolism study. Molecular network has emerged as powerful tool allowing metabolism study through organization and representation of untargeted tandem mass spectrometry (MS/MS) data in a graphical form. The aim of this study is to investigate amanitin metabolism using molecular networking. In vivo (four positive amanitin urine samples) and in vitro (differentiated HepaRG cells supernatant incubated with α-amanitin 2 µM for 24 h) samples were extracted and analyzed by LC-HRMS/MS using a Q Exactive™ Orbitrap mass spectrometer. Using molecular networking on both in vitro and in vivo, we have demonstrated that α-amanitin does not undergo metabolism in human. Thus, we provide solid evidence that a possible production of amanitin metabolites cannot be involved in its toxicity pathways. These findings can help to settle the debate on amanitin metabolism and toxicity.

Energy disorders caused by mitochondrial dysfunction contribute to α-amatoxin-induced liver function damage and liver failure.

Mushroom toxicity is the main branch of foodborne poisoning, and liver damage caused by amatoxin poisoning accounts for more than 90 % of deaths due to mushroom poisoning. Alpha-amatoxin (α-AMA) has been considered the primary toxin from amatoxin-containing mushrooms, which is responsible for hepatotoxicity and death. However, the mechanism underlying liver failure due to α-AMA remains unclear. This study constructed animal and cell models. In the animal experiments, we investigated liver injury in BALB/c mice at different time points after α-AMA treatment, and explored the process of inflammatory infiltration using immunohistochemistry and western blotting. Then, a metabonomics method based on gas chromatography mass spectrometry (GCMS) was established to study the effect of α-AMA on liver metabonomics. The results showed a significant difference in liver metabolism between the exposed and control mice groups that coincided with pathological and biochemical indicators. Moreover, 20 metabolites and 4 metabolic pathways related to its mechanism of action were identified, which suggested that energy disorders related to mitochondrial dysfunction may be one of the causes of death. The significant changes of trehalose and the fluctuation of LC3-II and sqstm1 p62 protein levels indicated that autophagy was also involved in the damage process, suggesting that autophagy may participate in the clearance process of damaged mitochondria after poisoning. Then, we constructed an α-AMA-induced human normal liver cells (L-02 cells) injury model. The above hypothesis was further verified by detecting cell necrosis, mitochondrial reactive oxygen species (mtROS), mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (Δψ m), and cellular ATP level. Collectively, our results serve as direct evidence of elevated in vivo hepatic mitochondrial metabolism in α-AMA-exposed mice and suggest that mitochondrial dysfunction plays an important role in the early stage of α-AMA induced liver failure.