Macrocyclic trichothecenes toxicity

However, the most interesting of the Baccharis species is most certainly B. coridifolia. This plant is well-known in Brazil as being one of that country s most toxic plants (49) and is a serious hazard to livestock who graze in pastures populated by B. coridifolia (49). Four separate collections were made of B. coridifolia (48). Three of these collections were "From several miles outside Curitaba and a fourth collection in a pasture near Santa Maria, the site of an earlier collection of 13. coridifolia (47), and several hundred miles away from Curitaba. ThTs latter collection and two of the three former collections contained appreciable quantities of roridins A and E. A third collection from near Curitaba appeared to contain no macrocyclic trichothecenes. From a 20 g sample of one of the collections of B. coridifolia... 

Ex vivo studies have revealed that trichothecenes can both inhibit and stimulate leukocyte function.12 For example, trichothecenes are toxic to alveolar macrophages,13 but drive differentiation of human myeloid leukemic cells.14 Dose-dependent decreases or increases in B- and T-cell mitogen responses are observable in lymphocytes from animals exposed to T-2 toxin, DON, or various macrocyclic trichothecenes these toxins similarly impair or enhance mitogen-induced lymphocyte proliferation in vitro.12 Rank order of inhibitor potency in rodent and human lymphocyte proliferation assays is Type D > Type A group > Type B group and is dependent on degree of acylation as well as of uptake and metabolism. 

Stachybotrys chartarum (previously also called S. atrd), the fungal cause of stachybotryotoxicosis and sick building syndrome, is a black mold. There are two toxic chemo-types of S. chartarum, one elaborating highly toxic macrocyclic trichothecenes and the other less toxic atra-nones and simple, but not macrocychc, trichothecenes (Andersen et al, 2002). Exposure may be by ingestion, e.g. exposure to contaminated straw, or inhalation as when mold grows in water-damaged homes or air ducts. 

Experimentally, the macrocyclic trichothecenes satra-toxin G, isosatratoxin F, and roridin A have been shown to cause nasal and pulmonary toxicity when administered intranasally or intratracheally to mice. Intranasal exposure of satratoxin G and roridin A induced apoptosis of olfactory sensory neurons resulting in atrophy of the olfactory epithelium and olfactory nerve layer of the olfactory bulb in the frontal brain (Islam et al, 2006, 2007). Alveolar-type II cells and alveolar macrophages were injured following intratracheal instillation of isosatratoxin F or Stachybotrys spores with marked changes in surfactant synthesis and secretion (Rand et al, 2002). 

Macrocyclic trichothecenes such as Satratoxin also were identified as causative toxicants. Since the 19th century, Alimentary Toxic Aleukia (ATA) or septic angina has been reported in the Soviet Union and symptoms of the disease were described as necrotic angina, leukopenia, hemorrhage, and exhaustion of bone marrow and death. 

Several studies investigated the in vivo toxicity of macrocyclic trichothecenes [135], It is assumed that their toxic effects are based on the inhibition of protein synthesis, with a slowly progressing respiratory depression and paralysis of skeletal muscles. The epidermal remains of these plant species that produce acute intoxication in rumiants were also quantified by microhistological analysis in the gastrointestinal content of sheep which had been experimentally poisoned [136]. 

Data sources (1) Ueno Y. Trichothecene mycotoxins Mycology, chemistry, and toxicology. Adv Nut Res. 1989 3 301-353. (2) Wannemacher RW Jr, Bunner DL, Neufeld HA. Toxicity of trichothecenes and other related mycotoxins in laboratory animals. In Smith JE, Henderson RS, eds. Mycotoxins and Animal Foods. Boca Raton, Fla CRC Press 1991 499-552. (3) Sharma RP, Kim Y-W. Trichothecenes. In Sharma RP, Salunkhe DK, eds. Mycotoxins and Phytoalexins. Boca Raton, Fla CRC Press 1991 339-359. (4) Jarvis BB. Macrocyclic trichothecenes. In Sharma RP, Salunkhe DK, eds. Mycotoxins and Phytoalexins. Boca Raton, Fla CRC Press 1991 361-421. 

There are a large number of different trichothecenes and ideally their analysis requires confirmation using GC-MS and analysis of the macrocyclic trichothecenes, which includes the verrucarins, ror-idins, and satratoxins, requires considerable experience and a specialized laboratory. However, well-established methods are available for individual trichothecenes of particular importance, such as T-2 toxin, diacetoxyscirpenol, deoxynivalenol, and neosolaniol. The large niunber of Fusarium trichothecenes are acylated derivatives of a much smaller niunber of parent alcohols, such as T-2 tetraol, scirpentriol, deoxynivalenol, and nivalenol, so another approach to their analysis is to hydrolyze the possibly complex mixture of trichothecenes to the parent alcohols and analyze these as their trimethylsilyl ethers. However, when this is done, there is often a poor correlation between total trichothecene content and observed toxicity, reflecting the large differences in the toxicity of different acyl derivatives even of the same parent alcohol. 

The pigments of the Fusaria have been described in Chapter 7. Many of the characteristic phytotoxic metabolites are the sesquiterpenoid trichothecenes (8.38) (see Chapter 5). The more highly hydroxylated members have considerable mammalian toxicity as well as phytotoxicity. Trichothecenes have been identified as metabolites of species from ten of the twelve sections of the genus Fusarium as classified by Booth. The trichothecenes occur with various combinations of oxygen substituents at positions 3, 4, 7, 8 and 15. Several trichothecenes contain macrocyclic esters linking C-4 and C-15. These are known as the roridins and verrucarins. 

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