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The Autophagy Creates Balance Mechanism between Apoptosis and Necroptosis: A Scorpion (Mesobuthus Nigrocinctus) Envenomation-Anti-Venom Administration Modelling in Mice

In the study, we aimed to show the role of autophagy which acting as a seesaw between apoptosis and necroptosis increasing and decreasing changes in certain vital organs under effects of envenomation by Mesobuthus nigrocinctus and anti-venom administration in mice. In group design, we previously classified totally 42 Albino mice into two main categories including 1st, 3th and 6th hours of envenomation and anti-venom administrated animals (at dosages of 20LD50, 30LD50 and 40LD50) before standard envenomation procudure. These were sub-divided into six groups including envenomed and anti-venom administrated mice (n = 6 at each one) were studied as well as not being evenomed and not anti-venom-administrated mice (n = 6) were used as control group (n = 6). At the end of 24 h after envenomation, all animals were sacrificed. Liver, kidneys, spleen, heart and lungs tissues were collected from all groups. After routine histopathological examination, expressions of mTOR as an autophagy activator, expressions of RIPK3 as a necroptosis activator, and caspase-3, caspase-9 as the markers of apoptotic cell death signals were evaluated by immunoperoxidase method in addition to DNA in-situ fragmentations by TUNEL method in aforementioned tissues. In envenomed groups, caspases and TUNEL reactions were low after envenomation in contrast to high RIPK3 expressions. mTOR expressions were remained at stable. In anti-venom administration groups, mTOR and RIPK3 expressions were more decreased in contrast to higher caspases exspressions and TUNEL expressions. In conclusion, we think that the scorpion envenomation drift solely the cells to necroptosis. And, under presence of anti-venom supply, the decreased mTOR expressions triggered autophagy and dependently that apoptosis was developed instead of necroptosis. We believed that this venom-antivenom administration study is a usefull role-model for better understanding of switch effect of autophagy between apoptosis and necroptosis.