**5.3 Nephrotoxicity**

Nephrotoxic agent orellanine is produced by the genus *Cortinarius* producing renal complications in which the symptoms may be delayed for 1–2 weeks after ingestion [75]. Nephrotoxicity can lead to the production of allenic norleucine usually observed in *Amanita smithiana*, but this can also be seen in other *Amanita* species. *Amanita smithiana* is well distributed in the United States [94], and their typical toxic symptoms include acute gastroenteritis leading to renal injury within 12–24 hours. Although some subjects with toxicity may require hemodialysis, in most patient's full recovery with appropriate supportive care is possible [8, 27]. Cases of seizures can be due to the presence of gyromitrin in *Gyromitra*, *Paxina*, and *Cyathipodia micropus* species, although can be less common in the latter two. Mushroom foragers in search for morel (*Morchella esculenta*) may accidentally ingest *Gyromitra* and toxicity could result from a metabolite, monomethylhydrazine, that may potentially lead to secondary product pyridoxine (B6) and up with GABA depletion. With GABA depletion, the occurrence of seizures may be intractable to anticonvulsant therapy and may require supplemental treatment including pyridoxine [78, 82].

Other manifestations due to the wide range of mushrooms that foragers could accidentally several other clinical manifestations have been documented and reported such as vertigo, somnolence, headaches, palpitations, dysrhythmias, rhabdomyolysis (*Tricholoma equestre*), methemoglobinemia, hemolysis (*Paxillus involutus*), erythromelalgia (acromelic acid), dermatitis (shiitake mushrooms), and cramping [4, 22, 55].

### **5.4 Toxicity evaluation, treatment, and management**

Toxicity evaluation is usually guided by many regulatory and clinical presentations, and may include:

Systematic and regular observation without testing in asymptomatic low-risk subjects, Serum electrolytes, kidney function testing, urinalysis, Serum creatinine kinase (CK), Liver enzymes, coagulation analysis, and complete blood count study [37, 44, 91]. In critical highly symptomatic subjects, target specific studies based on the symptoms of hepatic failure, altered mental status, hypoxia or respiratory distress can be performed [44]. Treatment of many possible symptoms mainly consists of supportive care. Depending on the period or time of ingestion, activated charcoal or chelating agents may be used for clinical intervention to provide some health benefit [82]. Acute gastrointestinal manifestation may benefit from rehydration and antiemetics in response to correction of any electrolyte imbalance [12, 20, 92]. For most patients showing adverse hallucinations, benzodiazepines administration may provide anxiolysis. Cholinergic toxicity may be managed from the administration of anticholinergic agents such as glycopyrrolate or atropine [76], with consideration of the administration of Atropine 0.5–1 mg IV adults or 0.01 mg/kg for cases of pediatric patients [29, 55].

In some specific cases, patients with refractory seizures due to gyromitra ingestion, administration of pyridoxine (B6) could be at 25 mg/kg IV can be given as treatment or as prophylactic for seizure control, or in some cases, benzodiazepines could be an alternative [21, 97] In case of patients ingesting amatoxin, consideration of the administration of N-acetylcysteine (NAC), silibinin, and penicillin can be used for treatment intervention. Clinical toxicologists and other health practitioners are advised to evaluate and manage patients in consultation with the local poison control (toxicovigilance center) or toxicology resource. Complications of ingestion depend on the toxin ingested and may range from dehydration in benign cases to renal failure, liver failure, and death in severe toxicities [89, 91]. Most mushroom poisonings result in mild to moderate gastrointestinal manifestations which include nausea, vomiting, and diarrhea. Other varieties of disorders that may lead to organ failure and even death her been reported and therefore it is important for foragers to know that there are many differing mushroom species with potential morphological similarities; very challenging in particular for those who are new in the mushroom collection as a new hobby. An understanding of local edible and toxic mushroom species is the key for amateur foragers, especially as the onset of just mild nausea will require evaluation as this could be an early manifestation of severe illness [3, 11].

## **5.5 Stages of amanita poisoning**

Amatoxin poisoning and stages of pathology have four phases as described.

Phase 1: The latency or lag period that may occur within 10–12 hours after ingestion, with the toxins absorbed via the digestive system and subject to the assault of the kidneys and liver.

Phase 2: Gastrointestinal phase. This is the onset of symptoms like severe abdominal pains, nausea, vomiting, diarrhea, delirium, hallucinations, hypoglycemia, and life-threatening dehydration.

Phase 3: Manifestation of severe gastrointestinal complications, a brief remission of symptoms after 3–4 days. The onset of jaundice, renal failures, toxic hepatitis, liver enlargement, liver hemorrhage.

Phase 4: Manifestation of lethality. Death can occur within 6–8 days after ingestion as a result of liver and kidney failure, followed by cardiac dysfunction.

The main challenge for the treatment of mushroom poison is the fact that there is no known antidote. Therefore, an immediate evacuation of gastrointestinal tract fluids, hemodialysis, slurry of activated charcoal, supportive measures, and if all else *Medicinal Mushroom of Potential Pharmaceutical Toxic Importance: Contribution… DOI: http://dx.doi.org/10.5772/intechopen.103845*

fails, administering a liver transplant can be timely [41, 50]. The use of thioctic acid in glucose delivered intravenously has been recommended by some experts. Bastien treatment like the use of vitamin C, nifuroxazide and dihydrostreptomycin, fluids, electrolytes, and penicillin are also applicable [89].

#### **5.6 Chemical test for mushroom toxicity**

The Meixner mushroom toxicity test can be used to determine whether a particular mushroom contains amatoxins. The stalk or cap is crushed to a piece of newsprint or other crude paper containing lignin. This crushed mass is allowed to dry and a small drop of concentrated hydrochloric acid is added. The presence of a blue color appearing in 5–10 minutes is an indication that amatoxins are present. This procedure involves an acid-catalyzed reaction of the lignin in the paper with the alpha amatoxin as the main structure as is well illustrated in **Figure 12** showing the structure of alpha amanita [5, 37, 40].

#### **5.7 Orellanine poisoning and symptoms**

Orellanine poisoning symptoms are similar to poisoning induced by amatoxins. However, muscular pain, excessive thirst, and painful urination may occur after 36 hours and could be delayed as long as 1–2 weeks after ingestion [86]. Orellanine invades and destroys the kidney tubules and in extremely severe cases, the treatment may require blood dialysis or kidney transplant. Lethalities in some cases have been

reported, and therefore orellanine poisoning needs to be considered in cases when kidney failure occurs from an unknown cause. Toxic cyclopeptides from cortinarins may be present in some cases and could play a vital role in *Cortinarius* poisonings. There are about 800 recorded species of *Cortinarius* in North America, all of which are health risks for consumers. Mushrooms produced by members of the genus *Cortinarius* are characterized by the possession of a cobweb-like cortina that is the remnant of the partial veil covering the gills and potentially neurotoxic to the autonomic nervous system. Coprine structure of Antabuse-like disulfiram-like poisoning and muscarine are illustrated in **Figure 13a** and **b**.

### **5.8 Toxin found in certain species of** *Coprinus*

*Coprinus atramentarius* also known as, *Coprinopsis atramentaria*, *Coprinus quadrifidus*, and the *Coprinopsis variegate* produce toxins that can bind to molybdenum and prevents normal acetaldehyde dehydrogenase activity, inhibiting ethanol metabolism [25]. Coprine poisoning is similar to acetaldehyde poisoning and symptoms begin 30 minutes to 1 hour after drinking alcohol when taken in 4–5 days after eating mushrooms or along with mushrooms. Symptoms include flushing of the neck and face, metallic taste in the mouth, tingling sensations in the limbs, numbness in the hands. Headache, throbbing of the neck veins, chest pains, nausea, vomiting, and sweating. Recovery from toxicity may be possible within several hours after ingestion [94].

### **5.9 Gastrointestinal irritants**

Many varieties of undetermined toxins associated with wild mushrooms have been reported. On ingestion, the toxins may cause gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal cramps that may occur after 30–90 minutes of ingestion. Symptoms generally may disappear spontaneously in 3–4 hours, and complete recovery can take place after 24 hours or more. Treatment strategy includes *Medicinal Mushroom of Potential Pharmaceutical Toxic Importance: Contribution… DOI: http://dx.doi.org/10.5772/intechopen.103845*

#### **Figure 14.**

*Amatoxins and phallotoxins in toxic mushroom Amanita phalloides. (a) The backbone structure (black) is the same in all the amatoxins and five variable groups (red) determine the specific compound. (b) Phalliodin and Phallacidin constitute the main component structure of Phallotoxin.*

emptying the stomach content, monitoring for possible dehydration, reduced blood pressure, and abnormal kidney function [17, 82].
