BIOL 4849 Mycotoxicosis

Mycotoxins BIOL 4849 - Summer 2010

Introduction

Mycotoxicosis • Mycotoxin – chemically diverse group of compounds – Produced primarily by molds • Some mushrooms • 300-400 different compounds by molds – Location • Hyphae • Conidia

Disclaimer: This lecture slide presentation is intended solely for educational purposes. Many of the images contained herein are the property of the original owner, as indicated within the figure itself or within the figure legend. These images are used only for illustrative purposes within the context of this lecture material. Use of these images outside the purpose of this presentation may violate the rights of the original owner. Dr. Cooper and Youngstown State University assume no responsibility for the unauthorized use of the material BIOL 4849 (Summer 2010) Copyright © 2010 Chester R. Cooper, Jr. contained herein.

Introduction (cont.) Introduction (cont.)

• Mycotoxins are thought to be part of an • Exposure routes environmental survival armament – Eating contaminated foodstuffs: very significant in • Various affects on protein, RNA, or DNA countries that rely on single grain food sources synthesis or membrane disruption • Growth on foodstuffs pre-harvest • Causes impaired cellular function or death • Post-harvest growth • Contamination of surfaces – Absorption through skin/contact: may induce necrosis as well as systemic effects • Possible bioweapons • Possible source of indoor health problems

Introduction (cont.) Introduction (cont.)

• Exposure routes (cont.) • “Toxic mold syndrome”: Special Notes – Inhalation of mycotoxins or fungal elements – The presence of a species of mold known to containing mycotoxins produce mycotoxins does not imply the presence • Significant industrial problem (e.g., saw mills) of a mycotoxin – need conditions favorable for mycotoxin production • Indoor mold problems (i.e., toxic mold syndrome) – Not all strains of a toxic mold species produce mycotoxins – Various other factors play roles: duration of exposure; host condition to include health, diet, genetics, etc.; and other factors

1 Mycotoxins BIOL 4849 - Summer 2010

Aflatoxins Aflatoxins (cont.)

• Over a dozen types of aflatoxins: B1 is main • Acute aflatoxicosis type – Associated with grains, particularly maize • Produced by Aspergillus species – Manifested as acute hepatitis – Mainly A. flavus and A. parasiticus – Lethal dose 10-20 mg – Infected foods include corn, figs, peanuts, • Chronic aflatoxicosis tobacco, and others – Aflatoxin B1 is involved in hepatocellular • Primary target is liver carcinoma

– Cytochrome P450 enzymes convert aflatoxins into – Aflatoxin B1 now classified as a Group 1 a form that binds both proteins and DNA carcinogen – Detoxification involves glutathione S-transferase – Risk factors include hepatitis B or C infection

Ergot Alkaloids Ergot Alkaloids (cont.)

• Various types of indole alkaloids having • Ergotism is very rare today various effects • Two types – Smooth muscle contraction – Gangrenous syndrome (St. Anthony’s fire): – Central sympatholytic activity constant ingestion of ergot leads to continuous – Peripheral α-adenergic blockade vasoconstriction, leading to ischemia and • Ergot is produced by the sclerotia of gangrene Claviceps, a pathogen of tall grasses and – Convulsive form: convulsions, fomications (feeling grains of insects crawling on the skin), disorientation, dementia; repetitive seizures can cause death • Ingestion of contaminated grains led to a • Thought to due to different toxic fungal strains number of historic outbreaks of ergotism BIOL 4849 (Summer 2010) Copyright © 2010 Chester R. Cooper, Jr. BIOL 4849 (Summer 2010) Copyright © 2010 Chester R. Cooper, Jr.

Ochratoxin Ochratoxin (cont.)

• Produced by Aspergillus ochraceus and other • Biochemical effects include Aspergillus species; Penicillium verrucosum – Inhibition of phenylalanine metabolism also produces this mycotoxin – Inhibition of mitochondrial ATP production • Ochratoxin A is main type – Stimulation of lipid peroxidation – Found in many seeds and nuts • Ochratoxin causes the following in animals: – Fat soluble, so when animals consume sources, – Nephrotoxicity (important in pork industry) the toxin remains in tissue – Hepatotoxicity – Humans can then consume the animals and ingest – Immunosuppression the mycotoxin – Teratogenesis/carcinogenesis

2 Mycotoxins BIOL 4849 - Summer 2010

Ochratoxin (cont.) Gliotoxin

• Has been linked to chronic nephritis in • Produced by Aspergillus fumigatus (no other humans (outbreak in Balkans) Aspergillus species), Penicillium spp., and • Listed as a category 2A carcinogen Candida albicans • Contains a disulfide bridge that conjugates with the thiol groups of proteins and generates reactive oxygen species by reducing the dithiol back to the disulfide bridge

Gliotoxin (cont.) Trichothecenes

• Biological effects include • Produced by various fungi, most notably – Immunosuppression Fusarium and Stachybotrys – Kills neutrophils and macrophages • More than 60 types, all highly toxic – Inhibits phagocytosis • Most notable types: T-2 toxin and vomitoxin – Various other immunological reactions • All are sequiterpenes having a 12,13-epoxy- • Virulence attribute of A. fumigatus trichothene ring • Different toxins inhibit different stages of protein synthesis

Trichothecenes (cont.) Trichothecenes (cont.)

• Toxins found • Black mold syndrome (Stachybotrys): no – Naturally occurring on plants conclusive evidence that toxins from this – Man-made (bioweapons) fungus are responsible for symptoms in – Sick building syndrome contaminated homes • 1942-1948: 100,000 deaths in former Soviet • However, T-2 toxin is a potential bioweapon Union due to alimentary toxic aleukia due to and reported used by Soviets in Afghanistan overwintered grain infected with Fusarium (“yellow rain”) • Similar syndrome in horses caused by Stachybotrys

3 Mycotoxins BIOL 4849 - Summer 2010

Mushroom Poisoning Mushroom Poisoning (cont.)

• Difference between mycotoxicosis and – Symptoms include: mushroom poisoning – essentially none • Abdominal cramps, nausea, and vomiting – Mycotoxicosis results from unknowingly ingesting • Followed by liver damage contaminated foodstuffs • Which can lead to liver failure, renal failure, and – Mushroom poisoning results from knowingly death during a 6-16 day period following ingesting a foodstuff that has been misidentified ingestion of the toxin • Best example: amanitin from the mushroom – Mortality is 20% in adults Amanita phalloides – Treatment can include liver transplant – Amanitin causes symptoms within 6-24 hours after – Amanitin inhibits RNA polymerase II ingestion

Mushroom Poisoning (cont.)

• Another mushroom mycotoxin of note: orellanine – Structurally similar to paraquat • Produces superoxide anions • Causing lipid peroxidation of membranes and depletion of NADPH – Leads to renal failure within 3 weeks • Other mushroom toxins are more well known for their hallucinogenic effects