Transdermal absorption of alpha amanitin toxin from amanita phalloides in mice

ABSTRACTTRANSDERMAL ABSORPTION OF ALPHA AMANITIN TOXIN FROM AMANİTA PHALLOİDES IN MICEMustafa Gani SÜRMENMaster of Science Thesis, Department of Medical PharmacologySupervisor, Assistant Professor Ertuğrul KAYAAmanita phalloides species is known to contain two main groups of toxins. Those are amanitin and falloidin. Amnitin group becomes effective with blocking RNA polymerase enzyme II found in eukaryotic cells. Since Alpha amanitin has a lethal effect on the majority of eukaryotic cells, it can be valuable as antiparasitic drug or antifungal drug. It can be used externally against ectoparasites. The critical point is that toxin must not be toxic for host via percutaneous application in terms of the mentioned therapeutic effectiveness of alpha amanitin. In this study, the likely absorption and toxicity has been researched for application percutaneous of alpha amanitinin. 1 mg/kg alfa amanitin has been administered percutaneously in mice and the results of percutaneous application has been compared with intraperitoneal application of 1 mg/kg alfa amanitin on account of toxicity. The toxicities of skin, liver and kidney have been researched by pathological examination. As for the amount of toxin, it has been studied by HPLC analysis. The toxicity and the toxin haven?t been found in the skin and organs of mice in the control group. Interestingly enough, the toxicity and the toxin a could not be found in percutaneous application group. After 24 hours councilman bodies and pyknotic cells were observed on intraperitoneal application and so toksisty existence was proved. In liver, kidney and blood maximum levels of alpha-amanitin were measured by same application method as 3.3(6 hours), 0.2(6 hours), 1.2(1 hours) µg/mL in turn. Eventually, it has been demonstrated that the toxin is not absorbed from mouse skin and the toxin doesn?t have any toxic effect via the percutaneous alpha amanitin application. Thence alpha amanitin may be used as therapeutic via a percutaneous application.Key words: Amanita phalloides, Alpha amanitin, Skin toxicity, HPLC.