Amatoksin kaynakli hepatotoksisitede epidermal büyüme faktörü tedavisinin incelenmesi

Amanita Phalloides mushrooms containing -AMA are responsible for the majority of fatal mushroom poisonings. EGF has a proliferative effect on cells of both mesodermal and ectodermal origin, especially keratinocytes and fibroblasts. According to experimental results EGF has a promising effect on liver toxicity. The purpose of this study was to investigate the effectiveness of EGF in both in vitro and in vivo models of -AMA-induced hepatotoxicity and to compare this with Silibinin, a known antidote. The cytotoxicity and oxidative stress parameters were evaluated on HuH-7 hepatocellular carcinoma cell line. In this study, the effects of varying concentrations of SIL (12.5, 25, 50 μM), EGF (1, 2, 4 μM), and combined treatments of SIL and EGF were investigated. Malondialdehyde, glutathione, catalase and superoxide dismutase were observed. In the in vivo part of the project. EGF efficacy in α-AMA intoxication treatment were evaluated in an in vivo animal model by comparing with Silibinin. 36 Balb-C male mice were used and divided into six groups. The groups were treated with α-AMA and determined antidotes given for each group and observed for 48 hours. Alkaline phosphatase, ALT, AST, GGT levels were studied with specific ELISA test kits. Liver tissues were taken at the end of experiment and observed for Liver Histological Damage Score and active caspase-3 levels. EGF has decreased MDA more when compared to SIL treatment. The combination treatment of SIL and EGF indicated a MDA profile similar to high concentration of EGF. Glutathione, superoxide dismutase and catalase experiments indicated that AMA exposure slightly decreased every parameter and treatment groups ranged effectiveness in a dose dependent manner. In vivo study results showed that higher dose of EGF (EGF1500) significantly lower the liver function tests and observed better reults on histomorphological analysis than α-AMA and EGF750 group both. EGF treatment showed promising results in α-AMA poisoning. Silibinin only and Silibinin and EGF combination have improved the liver function tests but cannot effectively treat the liver tissue. Therefore, it can be concluded that the use of