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Arhiv za Higijenu Rada i Toksikologiju 2004-Nov

[Chemistry and biological effects of gliotoxin].

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Ivan Kosalec
Stjepan Pepeljnjak

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Gliotoxin is a mycotoxin from the epipolythiodioxypipeazine family with biological active internal disulfide bridge. Gliotoxin has an antibacterial and antiviral activity, but it was discarded from clinical practice due to its toxicity. The most studied effect of gliotoxin is its influence on the cell of the immune system. Today, researches are focused on treating transplantation organs ex situ and making them immunologically silent. Its toxicity has been proven on several cells (macrophages, thymocites, splenocytes, and fibroblasts) causing apoptosis and necrosis and it has acted as inhibitor of several enzymes (farnesyl-transefases, NF-kappaB, and alcohol-dehydrogenases). Its mechanism of toxicity is connected with the production of mixed disulfide and covalent bonds, and oxidative effects. An important medical mould Aspergillus fumigatus and yeast Candida albicans can secrete gliotoxin in infected tissues and, because of the proven toxic effects of gliotoxin, it is suggested that gliotoxin can exacerbate mycoses (invasive aspergillosis or candidiasis). Gliotoxin can also affect the invasiveness of fungi and their dissemination from the primary site throughout the organism.

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