Chemistry and Biological Effects of Gliotoxin

Gliotoksin je mikotoksin iz skupine epipolitiodioksopiperazina s biološki aktivnim internim disulfidnim mostom. Gliotoksin ima antibakterijski i virucidan učinak (nekada se rabio kao antibiotik, no zbog toksičnosti je izbačen iz kliničke uporabe). Najviše proučavan učinak gliotoksina je na stanice imunosnog sustava, pa se pokušavaju gliotoksinom ili njegovim analozima obraditi presadci ex situ radi smanjenja učestalosti odbacivanja organa i tvorbe “imunosno tihih” presadaka. Toksičnost gliotoksina dokazana je na nizu staničnih linija (makrofazi, timociti, splenociti, fibroblasti) gdje izaziva apoptozu i nekrozu te inhibiranjem niza enzima (farnezil-transferazu, NF-κB, alkohol-dehidrogenazu). Toksičnost gliotoksina povezana je sa stvaranjem kovalentnih i miješanih disulfidnih veza te oksidativnim učincima. Gliotoksin tvore plijesan Aspergillus fumigatus i gljivica Candida albicans te se pretpostavlja da će tvorba ovog toksina, zbog dokazanih toksičkih učinaka na mjestu mikoze (invazivne aspergiloze i kandidijaze) imati učinak na egzacerbaciju mikoze odnosno pridonijeti invazivnosti gliotoksinogenih gljivica.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-κB, 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