Page 1115 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Trichothecenes Chapter | 75 1047

VetBooks.ir restricts weight gain by interfering with growth hormone Union used the same yellow dye. In fact, T-2 may have
been desirable chemical weapon because it has been very
signaling, i.e., alteration of the somatotropic axis (Lebrun
et al., 2015).
difficult to definitively detect its use after the fact. T-2
Alteration of the intestinal barrier: T-2 toxin causes may have also been used in the 1964 Egyptian attacks
an impairment of the barrier function of porcine intestinal against Yemeni Royalists and during the Iran-Iraq war of
epithelial cells (IPEC-J2 cells) and increased bacterial 1983 84 (Wannemacher and Wiener, 1997).
translocation in vitro (Akbari et al., 2016). T-2 toxin, Critically in relation to the chemical weapon potential
DON, 3-acetyl-DON and 15-acetyl-DON also decrease of T-2 toxin, it is the only member of the trichothecene
the transepithelial electrical resistance (a marker of barrier family that can be absorbed through the skin in sufficient
integrity) of IPEC-J2 and human epithelial colorectal ade- amounts to results in serious systemic toxicity
nocarcinoma cell (Caco-2) monolayers. DON also (Wannemacher and Wiener, 1997).
adversely alters the expression and/or distribution of Toxicokinetics: The toxicokinetics of T-2 toxin
enterothelial tight junction proteins in porcine jejunal conforms to the general trichothecene pattern, i.e., rapid
explants ex vivo and in vivo in pigs, mice, and broiler bioavailability following ingestion and inhalation.
chickens. Importantly, T-2 toxin undergoes various combinations of
deacylation, C-12/13 deepoxidation, and oxidization by
ruminal microflora, intestinal bacteria and by many differ-
T-2 Toxin
ent cell types. Metabolism is generally detoxifying: T-2
T-2 toxin, a member of the Type A trichothecene family, toxin is about 1.5 1.7 times as toxic as HT-2, which is
is predominantly associated with Fusarium spp. growth 4.8 times as toxic as T-2 tetraol (Ueno et al., 1973).
on wheat and corn (Adhikari et al., 2017). T-2 toxin and Ruminal and intestinal microflora metabolism is generally
its metabolite HT-2 has also been reported in barley, rice, detoxifying and is an important protective effect
soy beans, oats, and products produced from these grains. (Adhikari et al., 2017; Wannemacher and Wiener, 1997).
The chemical weapon potential of T-2 toxin was recog- Because of ruminal detoxification, monogastric ani-
nized in World War II following an outbreak of T-2 toxin mals are generally more susceptible than ruminant spe-
alimentary toxic aleukia (ATA) in Orenburg, in the cies. Tissue distribution studies demonstrate that the liver
Russian Urals. The outbreak was due to consumption of is the quantitatively most important organ for trichothe-
Fusarium spp. infected, overwintered wheat and millet. cene metabolism (Wannemacher and Wiener, 1997). The
From 1942 to 1947 ATA was responsible for the death of major metabolites are HT-2 toxin and its hydroxyl and
about 10% of the population of Oregnburg (100,000 glucuronide metabolites and T-2 tetraol and its glucuro-
human fatalities) (Wannemacher and Wiener, 1997). A nide. Hepatic microsomal carboxyl esterase is an impor-
similar, ATA like disease called Akakabibyo (called tant catalyst of T-2 toxin metabolism. Metabolite
“bean-hulls poisoning” in the equine cases) was subse- excretion occurs via the urine and bile. Very little T-2
quently reported in Japan (Ueno et al., 1973). In this out- toxin is excreted intact.
break neosolaniol (a metabolite of T-2 toxin) and T-2 Modes of action: Like all of the important trichothe-
toxin were detected in bean hulls contaminated with cenes, T-2 toxin is a site of first contact irritant. This
Fusarium solani. This outbreak demonstrated an impor- results in serious hemorrhagic ulceration and necrosis of
tant feature of T-2 toxin: it often cooccurs with its meta- the gastrointestinal tract (GIT) following ingestion.
bolites (e.g., HT-2 toxin, neosolaniol, etc.) and other Disruption of the intestinal microflora and associated sec-
trichothecenes such as diacetoxyscirpenol. When T-2 ondary effects can occur. Cytotoxic damage in the liver,
toxin contaminated products are blended with different heart, kidneys, lymphoid tissues, bone marrow, and
batches of grain, multiple different mycotoxins can cooc- peripheral ganglia occurs as the toxin undergoes distribu-
cur resulting in mixed mycotoxin poisonings. tion in the circulation. The key toxicological modes of
Controversy remains regarding weaponization of T-2 action of T-2 toxin are inhibition of protein synthesis and
toxin by the Soviet Union and the possible use of such increasing oxidative stress. The secondary consequences
weapons by its client states in Laos, Cambodia (“yellow of these are widespread and include: DNA/RNA damage,
rain” incidents from 1975 to 1981) and Afghanistan reduced DNA/RNA synthesis, impaired amino acid
(Wannemacher and Wiener, 1997). In these cases T-2 metabolism, cytotoxicity, impaired energy metabolism
toxin may have been mixed with various combinations of due to disruption of the TCA cycle, and severe
phosgene, phosgene oxide, sarin, soman, mustard gas, immunosuppression.
alpha-chlorbenzylidene malonitrile (CS), or 3- Acute toxicity: T-2 toxin is amongst the most toxic of
quinuclidinyl benzilate (BZ). Unambiguous identification the trichothecene mycotoxins. As with all of the trichothe-
of these weapons was difficult because many different cenes, the most commonly observed phenomenon in vet-
chemical weapon combinations prepared by the Soviet erinary medicine is feed refusal and associated secondary