Plants: Mushrooms

Introduction

There are more than 200 different species of mushrooms, most of which are toxic and can be found natively in tropical and subtropical climates. Even though mushroom poisonings can result from the misidentification of a poisonous species, the majority are due to intentional ingestions.

A classification system has been established to group the mushrooms based on clinical effect, taxonomy and phenotype. Please click here for a comprehensive overview of all 15 mushroom classifications (Groups 1 – 15). In the interest of time, we will be looking more closely at psilocybin-containing mushrooms, or “magic mushrooms” (Group 6).

Biotransformation and MOA (1) 

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The psychoactive component of Group VI mushrooms, psilocybin, is rapidly and completely hydrolyzed to psilocin in vivo. Once converted to psilocin, psilocybin exhibits agonistic and antagonistic actions on 5-hydroxytryptamine (5-HT) receptors. The figure to the left shows how psilocybin and psilocin are structurally similar to serotonin. Through agonistic activation of 5-HT2a receptors (high affinity) and 5-HT1 receptors (low affinity), psilocybin causes several psychotomimetic effects.

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Binding to the 5-HT receptors can prevent the reuptake of serotonin (causing increased synaptic activation of receptors) or block the activity of serotonin (resulting in depressive activity). Serotonin receptors are located in several critical areas of the brain.

Toxicokinetics

Toxicological profile of poisonous, edible and medicinal mushrooms here.

Target organs:

Psilocybin-containing mushrooms target the CNS and GI. Mushroom classifications exert different systemic effects. Click here for a comprehensive overview of target organs by mushroom classification.

Carcinogenicity

Mushrooms contain trace amounts of carcinogenic compounds in raw form. The following compounds have been linked to mushroom species:

  • Agaritine (AGT) is a group 3 carcinogen found in the mushroom species Agaricus (4)
  • Formaldehyde is a naturally occurring compound found in shiitake mushrooms (5)
  • Hydrazine found in portobello mushrooms (4)

Biomarkers & Mushroom Identification

  • Diagnosis must be made upon clinical presentation
  • There are no tests or labs available to identify or quantify total ingested dose
  • Unable to use HPLC, TLC, GC, or GC-MS
  • Symptomatology assessment should be made by mycologist or toxicologist
  • Most important anatomical features of edible and poisonous mushrooms (1):
    • Pileus: broad, caplike structure from which hang the gills, tubes or teeth

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    • Stipe: long stalk or stem that supports the cap (not present in all species)
    • Lamellae (or gills): structures found on the undersurface of pileus. How the lamellae attaches to the stipe is key for a positive identification
    • Volva: partial remnant of the vein found around the base of the stipe (not present in all species)

If Mushroom is Unknown… (1)

  1. Triage: Immediately confirm whether ingested mushroom is of the high-morbidity species based on anatomical features and clinical symptoms
  2. Collect and transport:
    • Attempt to either collect either the mushroom, a photo, or a detailed description of its features
    • Transport mushroom in dry paper bag (cannot be moistened or refrigerated)
  3. Spore print: make a spore print of the mushroom cap (if available) by placing pileus spore-bearing surface-side-down on a piece of paper for 4-6 hrs
    • Spores will collect on paper and be analyzed by color
    • White spore prints are more easily visualized
  4. Contact mycologist for proper identification

Signs and symptoms of toxicity (1, 2)

  • CNS: ataxia, headache, nausea/vomiting, hyperkinesis, visual illusions, and hallucinations
  • PNS: myalgia, weakness
  • GI (onset <5 hrs): tachycardia, mydriasis, anxiety, lightheadedness, tremor and agitation. Return to normalcy within 6 – 12 hrs
  • Rare: Acute kidney failure, seizures, cardiopulmonary arrest

Click here for a comprehensive overview of signs/symptoms.

Treatments for Group VI ingestion (1)

  • Hospital admission: for anyone who shows GI symptoms and remains symptomatic for hours
  • Hallucinations: benzodiazepines (supportive care)
  • Ingestion: activated charcoal
    • If nausea/vomiting persist, an antiemetic is recommended to ensure the patient can retain the activated charcoal
  • Life-supportive measures: fluids, electrolytes, dextrose repletion

Summary

Resources

  1. Goldfrank LR. Mushrooms. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw-Hill; Accessed July 22, 2020. https://accesspharmacy-mhmedical-com.proxy.lib.ohio-state.edu/content.aspx?bookid=2569&sectionid=210276854
  2. Tran HH, Juergens AL. Mushroom Toxicity. [Updated 2020 Mar 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537111/
  3. Jo WS, Hossain MA, Park SC. Toxicological profiles of poisonous, edible, and medicinal mushrooms. Mycobiology. 2014;42(3):215-220. doi:10.5941/MYCO.2014.42.3.215
  4. Hashida C, Hayashi K, Jie L, Haga S, Sakurai M, Shimizu H. Nihon Koshu Eisei Zasshi. 1990;37(6):400-405.
  5. Mason DJ, Sykes MD, Panton SW, Rippon EH. Determination of naturally-occurring formaldehyde in raw and cooked Shiitake mushrooms by spectrophotometry and liquid chromatography-mass spectrometry. Food Addit Contam. 2004;21(11):1071-1082. doi:10.1080/02652030400013326

Solvents: Carbon Tetrachloride

Vintage Screw Top Bottle w Label CARBON TETRACHLORIDE Poison Skull ...

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Carbon tetrachloride is a clear, nonflammable, heavy liquid used as an industrial solvent and reagent with restricted commercial use. It is used in fire extinguishers, dry cleaning agents, grain fumigation, military smokescreens and as a raw material during the manufacturing process of other chemicals (1).

 

 

 

The toxicity profile has long been characterized with increased awareness and subsequent product bans:

  • 1970: banned in consumer products
  • 1978: banned in aerosol products
  • 1986: banned in grain fumigation except for preserving museum artifacts (3)

Today, CCl4 is mainly used in the synthesis of chlorofluorocarbons (CFCs), which are used as heat transfer agents in refrigerating equipment and as aerosol propellants (2).

Exposures

CCl4 vapors can be inhaled occupationally by workers or via direct skin contact while the general population may be exposed by breathing air, smoking cigarettes, consuming food/water and contact with contaminated soil (3).

Mechanism of Action (3, 4)

CCl4 is metabolized primarily in the liver where it is converted to the trichloromethyl radical (CCl3) via the cytochrome p450 isoform CYP2E1. The CCl3 radical then does the following:

  • Lipid peroxidation: free radicals travel to smooth ER and cause lipid peroxidation and other forms of oxidative damage by attacking and destroying polyunsaturated fatty acids. This disrupts the permeability of mitochondria, endoplasmic reticulum and plasma membranes. Without the ability to exchange ions, there is cellular accumulation of calcium resulting in further cell damage. This occurs within the first 10-15 minutes of exposure. 
  • Biotransformation: Converts to trichloromethyl peroxy radical (OOCCl3) and chloroform (CHCl3). Additionally, it is oxidized to produce hexachloroethane (Cl3CCCl3)

These radicals then bind to cellular molecules (nucleic acids, proteins, lipids) and impair processes including cellular respiration, lipid metabolism and fatty degeneration. Free fatty acids then accumulate in the liver resulting in hepatomegaly and other hepatic toxicities. This occurs 10 – 12 hours after exposure.

CCl4 also activates tumor necrosis factor (TNF) alpha, nitric oxide (NO) and transforming growth factors (TGF)-alpha and beta which trigger a signaling cascade resulting in fibrosis and cell death.

Target Organs

Target organs include: endocrine (glands, hormones), liver, CNS, eyes, lungs, liver, kidneys, skin (2).

Treatments (2, 3) 

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  • Anecdote: N-acetylcysteine may reduce severe complications
  • Emergency Treatment:
    • Decontamination
    • Artificial respiration (i.e. demand-valve resuscitator, bag-valve-mask device, or pocket mask)
    • Do not induce vomiting
  • Basic Treatment:
    • Administer oxygen
    • Eye contamination: flush eyes immediately with water or irrigate with 0.9% saline (NS)
    • Ingestion: rinse mouth and administer activated charcoal
    • Dermal Exposure: cover burns with sterile dressings after decontamination
  • Advanced Treatment:
    • Orotracheal or nasotracheal intubation
    • Positive-pressure ventilation techniques
    • Vasopressors if patient is hypotensive
  • Chronic Exposure: no treatment exists

Biomarkers

CCl4 can be detected by gas chromatography in blood, serum, and adipose tissue (3). That being said, any detectable blood level of CCl4 is indicative of exposure. Indirect biomarkers of CCl4 exposure include baseline liver function tests, liver injury tests and renal function tests. In suspected high exposures, clotting studies, chest X rays and electrocardiograms are indicated (3).

CCl4 toxicity Summary

References

(1) Morrison RD, Murphy BL, Doherty RE. 12 – chlorinated solvents. Environmental Forensics. 1964:259-277. http://www.sciencedirect.com/science/article/pii/B9780125077514500343. doi: https://doi.org/10.1016/B978-012507751-4/50034-3.

(2) National Center for Biotechnology Information. PubChem Database. Carbon tetrachloride, CID=5943, https://pubchem.ncbi.nlm.nih.gov/compound/Carbon-tetrachloride#section=Overview (accessed on July 8, 2020)

(3) “Case Study 8: Carbon Tetrachloride Toxicity.” Institute of Medicine. 1995. Environmental Medicine: Integrating a Missing Element into Medical Education. Washington, DC: The National Academies Press. doi: 10.17226/4795.

(4) Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33(2):105-136. doi:10.1080/713611034