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    Dermal absorption and toxicity of alpha amanitin in mice
    (Informa Healthcare, 2014) Kaya, Ertugrul; Surmen, Mustafa Gani; Yaykasli, Kursat Oguz; Karahan, Selim; Oktay, Murat; Turan, Hakan; Colakoglu, Serdar
    The fungus Amanita phalloides is known to contain two main groups of toxins: amanitins and phallotoxins. The amanitins group effectively blocks the RNA polymerase II enzyme found in eukaryotic cells. As alpha amanitin has a lethal effect on the majority of eukaryotic cells, it can be valuable as an antiparasitic or antifungal drug. It can be used externally against ectoparasites. It is critical that percutaneous applications of the alpha amanitin toxin are not harmful to the recipient. In this study, the absorption and the toxicity of percutaneous and intraperitoneal (ip) applications of 1 mg/kg alpha amanitin to mice were compared. Potential skin, liver and kidney toxicities were investigated through pathological examination. HPLC analysis was used to determine the amount of the toxin. No toxicity or toxin were found in the skin, liver, or kidneys of the mice in the control group. Interestingly, the percutaneous application group also showed no toxicity, and the toxin was not present in this group. After 24 h, Councilman-like bodies and pyknotic cells were observed in the mice in which alpha amanitin was applied intraperitoneally, demonstrating the presence of toxicity. Peak levels of alpha amanitin (mu g/mL) in the liver, kidney, and blood in the ip application group were measured at 3.3 (6 h), 0.2 (6 h) and 1.2 (1 h), respectively. The results demonstrated that the toxin was not absorbed through the skin of the mice and that the percutaneous application of alpha amanitin did not have any toxic effects. Thus, alpha amanitin may be administered percutaneously for therapeutic purposes.
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    Gene expression profiles for apoptotic and necrotic pathways during Amanita phalloides intoxication in mice
    (Istanbul Univ, Fac Pharmacy, 2022) Karahan, Selim; Atli, Zehra; Kaya, Ertugrul; Ozdemir, Feride; Boga, Mehmet; Izgi, Sevcan
    Background and Aims: Amanita phalloides is the deadliest toxic mushroom in the world and causes death from acute liver failure. alpha-amanitin (alpha-AMA), the most potent toxin, inhibits RNA polymerase II in hepatocytes, stops protein synthesis, and causes hepatotoxicity. However, the information about the mechanisms underlying hepatotoxicity caused by alpha-AMA is quite inadequate. This study aims to reveal the complex necrotic and apoptotic mechanisms occurring in mouse hepatocytes de-pending on A. phalloides exposure time in vivo.Methods: BALB-c male mice were divided into 5 groups (n=7): control, alpha-AMA-2, alpha-AMA-12, alpha-AMA-72, and alpha-AMA-96 groups. A poisoning model was created by oral administration of A. phalloides mushroom extract containing 10 mg/kg of alpha-AMA to mice and they were sacrificed after 2, 12, 72, and 96 h. Then, TNF-alpha, Bax, caspase-3, and Bcl-2 gene expression levels in liver tissues were examined by the RT-qPCR method. Time-dependent damage to liver tissues was also evaluated histopathologically.Results: RT-qPCR results showed that proinflammatory cytokine TNF-alpha mRNA expression levels increased in mouse liver tissues at 2 and 12 h afterA. phalloides administration compared among the groups. BaxmRNA expression levels increased in the 12 and 72 h afterA. phalloides ingestion. It was observed that caspase-3 mRNA expression levels increased in the 72 and 96 h groups compared among the groups, while Bcl-2 mRNA expression levels decreased in the 72 and 96 h groups.Conclusion: Our findings showed that necrotic mechanisms develop in the early period afterA. phalloides mushroom poison-ing, and then apoptotic mechanisms are effective. In conclusion, understanding the mechanisms of A. phalloides-induced hepatotoxicity will provide important information for new treatment strategies to be developed.
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    Phosalone Toxicity on Liver and Pancreas: Role of Vitamins E and C
    (Asian Journal Of Chemistry, 2013) Demirin, Hilmi; Gokalp, Osman; Kaya, Ertugrul; Buyukvanli, Bora; Cesur, Gokhan; Ozkan, Aybars; Kaya, Murat
    Phosalone (6-chloro-3-[diethoxyphosphinothioylsulfanylmethyl]-1,3-benzoxazol-2-one) is one of the most commonly used organophosphorus pesticides in the peat control of crops. Subchronic phosalone exposure was evaluated for its effects on the serum activities of some enzymes concerning hepatic and pancreatic damage including aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), cholinesterase (ChE); and finally protective effects of combination of vitamins E and C in 24 wistar-albino rats. Experimental groups were as follows: control group (n = 8); a group treated with 120 mg/kg body weight phosalone (P group, n = 8); and a group treated with 120 mg/kg body weight phosalone + vitamin E + vitamin C (P+V group, n = 8). The P and P+V groups were treated orally with phosalone on 5 days a week for 4 weeks. The serum activities of the above mentioned enzymes were analyzed. In the samples phosalone significantly increased the activities of ALT, LDH and decreased ChE (p < 0.05). However no significant change was detected for the remainder enzymes (p > 0.05). In the P+V group, ALT and LDH activities were significantly increased and ChE decreased (p < 0.05). It is concluded that subchronic phosalone causes rat liver damage to an extent, which is somewhat reflected on the liver enzymes. Furthermore, a combination of vitamins E and C can reduce the toxic effects of phosalone on liver tissue of rats.