Tox- Mycotoxins 2

kelseyfmeyer's version from 2016-10-02 23:32

exotoxins: sole toxin being ingested by animal

Question Answer
with fungal exotoxins, which are pretty common, you don't need a ____ to cause clinical signsdont need an infection to cause clinical signs.
fungal exotoxins: how big are the molecules? what environmental conditions are they resistant against (physical and biochemical stability)They have a low molecular weight so they are non-immunogenic unless bound so a larger molecule (hapten). PHYSICALLY: heat resistant HOWEVER UV labile (as in degraded easily by UV). BIOCHEMICALLY: The have a high pH tolerance but do undergo enzymatic degradation/biotransformation, and if the biotransformed by a plant, it is called glycosinolation (can mask the mycotoxins) and are highly lipophilic (meaning highly bioavailable aside from FB1)
what are exotoxins/how do they affect the body?It is just the toxin contaminating the feed- NOT concurrently infected with the fungus as well. (fungus is gone but toxin remains)
how well does feed processing deal with exotoxins?doesnt really help bc toxins are stable up to like 300*C (perhaps irradiation will help tho, in breaking it down)
The era of mycotoxin research-- what are possible CSs of acute intoxications?Bile duct proliferation, Fatty liver infiltration, Reduced vitamin A content, Immunosuppression
what are the clinical signs of turkey X dz?Weight loss, Reduced feed conversion, Anorexia, Jaundice, Depression (turkey X: This disease was the turning point for the use of the term mycotoxin. In the 1960s, about 100,000 turkey poults died near London, England due to peanut meal that was contaminated by Mycotoxins produced by Aspergillus flavus. Studies showed that the age group that was most affected was turkeys from two to twenty weeks old. Some of the first signs of Turkey X were neurological symptoms and coma, which would result in death)

Ochratoxin A

Question Answer
which two species of fungi produce ochratoxin A?Aspergillus ochraceus and Penicillium verrucosum
what are common food items what ochratoxin A?Found in wheat, wine and coffee
which animal is most sensitive to OTA?pigs
what are clinical signs of OTA?Nephropathies (PU/PD), (balkan endemic nephropathy, UT tumors), Hypothermia, Immunosuppression, Teratogenic
how does OTA affect poultry? (CSs?)in poultry is a a REALLY big problem- huge economic losses. In poultry you will see pale kidneys and gray carcasses
what is one of the reasons OTA seems to focus damage on the kidneys?has a super long elim half life in the kidney (is metabolized there if i remember correctly)
what is up with the trend of OTA in our companion animals? are dogs or cats more affected?we are leaning towards a more balanced diet for them-- which means more grains in their food-- and OTA is in grains so dogs/cats being more exposed to OTA in their diet (Foods in dog/cat food that carry the OTA: Cereals - peanuts/nuts - blood products - porcine kidneys/livers) Dog will have higher conc of OTA in their food bc cat is obligate carnivore so have less grain in their diet.
what are the main 2 DDX of OTA for a companion animal?age-related renal insufficiency, urinary tract infections, gentamicin tox, cadmium tox
which part of the nephron seems most affected by OTA?prox tubular damage most commonly seen, and with inc doses then start to see more distal tubular damage.


Question Answer
what are the two fungi which are Fumonisins?FUSARIUM VERTICILLIOIDES/MONILIFORME
fumonisins produce a wide variety of toxins, such as:FUMONISIN B1, B2, B3 - FUSARINIC ACID - FUSARINS - GIBBERILINS - MONILIFORMIN
what food product(s) do fumonisins infect?EXCLUSIVELY IN CORN.
what equine problem do fumonisins cause?Equine leukoencephalomalacia
what are the CSs of equine leukoencephalomalacia?...only CS is sudden death lol (and affects entire brain tissue, not just one place is targeted)
what can happen if humans consume fumonisins?can cause malformed children, ABSOLUTE VIT B, esophageal carcinomas, neural tube defects
what can fumonisins do to pigs?pulmonary edema
what vitamin do fumonisins affect/ how ?leads to an ABSOLUTE VIT B deficiency.
what should you know about the toxins made by fumonisins?its just this type of fungal species which produce a VARIETY of toxins.
what is currently the most prominent toxin in feed materials?Fusarium toxins (FUMONISIN B1, B2, B3 - FUSARINIC ACID - FUSARINS - GIBBERILINS - MONILIFORMIN)
So fumonisin tox can lead to sudden death in horses, depending on the exposure and sp, there can be quine subtle CSs. where it is hard to find true cause of problem....but the OVERALL result is...economic losses in farm animals :(
what are some of the subtle ways (CSs) that fumonisins lead to economic losses on farms?see impairment of intestinal health (poor nutrient utilization) (<---actually see this with a lot of mycotoxins) and also seem to have a DIRECT effect on the immune system (esp GI immune system) and can cause Increasing prevalence of viral and bacterial diseases (increased use of antibiotics) and vaccination failures
so if you have a farm where usually a disease responded nicely to vaccination, but it doesn't seem to be working in this case, you can suspect...fumonisin/ mycotoxicosis
what are the main groups that you can break fumonisins into?They are the Trichotecenes: and Type A and Type B (Epoxy-trichothecene group A, Epoxy-trichothecene group B)
what is common structue between all the Trichotecenes (one of the groups of fumonisins)They all have a Typical epoxide moiety (in the C12, 13 position) and epoxides lead to lipid peroxidation, which leads to oxidative stress, etc.
what is the difference between the Trichotecenes type A and B?Type A has a lack of keto group at C8. Type B HAS a keto group and C8 <--said not as important as just knowing that there are 2 types and they both have epoxides
Epoxy-trichothecene group A: What are the clinical signs of an infection with the group A toxins? (which toxin is responsible for these CSs?)(T2 toxin) Skin lesions: dermatitis, Conjunctivitis, Bloody diarrhoea, Petechia, Atrophy of spleen and thymus, immunosuppression
what is the most important group A epoxy-trichothecene toxin, and what CS is it responsible for?T2 Toxin which is responsible for the skin lesions (dermatitis) seen with a Group A intoxication. (also causes the Conjunctivitis, Bloody diarrhoea, Petechia, Atrophy of spleen and thymus, immunosuppression is how he made it sound) (the other toxins listed on the slide are Epoxytrichotecene, HT-2 toxin, Diacetoxyscripenol (DAS) )
what is the most important Group B expoy-trichothecene toxin, and what CSs is it responsible for?Deoxynivalenol (DON) aka vomitoxin Clinical signs: vomiting (hence vomitoxin, lol) - reduced feed intake - growth retardation - GIT lesions - immunosuppression
what is the toxin you def need to know from Group A, and from Group B?GROUP A: T2 TOXIN. GROUP B: DON (deoxynivalenol aka vomitoxin)
DON (deoxynivalenol aka vomitoxin) is the toxin from which group of epoxy trichothecenes, and what is it's MOA?from GROUP B-- complicated MOA but basically causes altered neuroendocrine signalling having an effect on growth hormone, and the growth hormone signalling, which leads to the growth retardation and reduced feed intake. Also causes pro-inflammatory cytokine gene induction which has a direct immediate effect on the GI tract (and other systems), there is disruption of the growth hormone axis (bc of the neuroendocrine signalling) and an altered gut integrity (gut integrity related to induction of proinflammatory mediators) [neuroendorine--gut--immune system tie in basically]
which toxin is super painful?T2 toxin (group A) (historically has been used as a warfare agent)
Why is T2 toxin (group a) so painful? What CSs does it cause again?SUPER painful bc directly stimulates the nociceptors. Causes Skin lesions, pain, loss of appetite. Like a single drop of T2 toxin can cause pain for weeks.
what is the differential diagnosis for T2 toxin?Stachybotrys chartarum aka satratoxin
Stachybotrys chartarum aka satratoxin is the ddx for what? What are the CSs of this, and where does it coem from?T2 toxin from epoxy trichothecenes. Satratoxin also causes Skin lesions, pain, loss of appetite, and comes from Black moulds in straw, hay and indoor environments-- but it is not as painful as the T2 toxin.
T-2 toxin - clinically relevant effects? (3)(1) Dermatotoxicity with activation of nociceptors (pain) (2) Haematotoxicity (pancytopenia) - bleeding (3) Immunosuppression (vulnerability to infections)
why is T2 toxin so difficult to dx?Rapid metabolism - short half-life. kinda a "hit and run" toxin. (so although it stays at nociceptors for like 2-3 weeks, you can't find it in the plasma anymore)
which species is MOST sensitive to T2 toxins?cats
T2 toxicity HAS been reported in dogs and cats because (where does it come from?) and what is the ddx for it? (why?)been found in dog and cat feed (remember T2 toxin is epoxide trichothecene toxin is fumosin is corn) and DDX is Idiosyncratic potentiated sulfonamide toxicity, since that also causes pancytopenia and hemolytic anemia.... (T2 toxin also causes CV reports in cats)
DON aka Deoxynivalenol aka vomitoxin-- who is most sensitive?Pigs are the most sensitive species
what are the clinical signs for DON aka Deoxynivalenol aka vomitoxin and what do the CSs depend on?Dose-dependent clinical signs: (1) Abdominal distress
WHAT IS THE MOST PREVALENT TOXIN IN THE NORTHER HEMISPHERE?DON aka Deoxynivalenol aka vomitoxin (group B) (<800ppb) (2) Immune suppression (>100ppb) (3) Reduced feed intake (>1000ppb) (4) Feed refusal (>1300ppb) (5) Vomiting (>2000ppb)
what are the pharmacokinetics of DON aka Deoxynivalenol aka vomitoxin like? (how bioavailable? how much protein binding? how is it metabolized? what is the elim half life? about how long to clear it?)Bioavailability: 80% - rapid absorption!! Minimal protein binding (hence very bioavailable), Glucuronidation in the liver, Elimination half-life: 4 hrs. Total clearance >>24 hrs??
vomitoxin leads to what prob?GI tract dysfunction/inflammation with dec utilization of nutrients and dysregulation of immune system.
DON deoxynivalenol: impairment of immune function--> explain how this worksHappens through intracellular signalling, leading to induction of pro-inflammatory cytokines, loss of barrier function (bc of inflammation), impairment of glucose and Na+ cotransport. (bc of immune effects, also inc risks of infections and vaccination failures) There is Gut associated local immune response: (not said in class but on slide:) Activation of MAPK--> Upregulation of IgA expression--> Upregulation of transcription factors (NFkB)--> Induction of pro-inflammatory cytokines--> Induction of COX-2--> loss of barrier fxn due to inflammation and Impairment of glucose-Na + co-transport
explain what it means that DON is a "masked mycotoxin"Well, DON is toxic for plants-- so they detoxify it via the plant glycosinolation path. This detoxifies it in the plant. But then gets REACTIVATED in the mammalian system (conjugation reaction leads to reactivation of DON in animal system) AND also can't be quantified in the plant bc deactivated.
DON toxicity in dogs and cats: When given don in experimental studies, they found what side effects and what did the animal do?Reduced feed intake and vomiting (dose dependant) and if give a choice between DON and non-DON food, always picked non-DON (they can prolly taste it)
who is most sensitive to DON? who is most sensitive to T2?DON: pigs. T2: cats
DDX in dogs and cats for DON toxicity? age-related hypertension in cats, urinary tract infections in dogs (And all kinds of other GI probs he said)


Question Answer
in what food is Z. found?Found in maize, CCM, grain and grass
what other compound is Z. similar to?estradiol-- meaning it has high affinity for estrogen receptor! (binds to receptor, moves into nuc, binds DNA, leads to production of proteins)
CSs of Z?Clinical signs of hyperestrogenism (bc its similar to estradiol and can bind to the estrogen receptor) so huge swollen vulvas etc.
how is Z. metabolized? what are the products of metabolism?since similar to estradiol w steroid backbone, metabolized via hydroxysteroid dehydrogenase. also glucoronidation (so Glucuronidation and hydroxylation) Metabolized into alpha-zol and beta-zol
how potent is Z and its products?alphaZ > Z > betaZ (since metabolite is more toxic-- BIOACTIVATION)
most sensitive species to Z?pigs (again-- remember swollen piglet vulva)
why are pigs most sensitive to Z?bc they mainly metabolize Z into alpha-ZOL which is most toxic.
what are two unique ways that Z exposure can happen? intra-uterine exposure and perinatal exposure (colostrum/milk)
what is bioavailibility like for Z?high bioavail- > 80%, rapid absorption and low plasma protein binding
what is elim half life like for Z?LONG! 86 hrs