Chronic treatment with Wnt agonist was started either immediately after hepatotoxic insult ("early treatment") or when signs of ALF had developed ("late treatment"). Given the importance in the liver biology of Wnt/beta-catenin signaling pathway, we hypothesized that its stimulation could enhance hepatocyte regeneration and attenuate the course of thioacetamide (TAA)-induced ALF in Lewis rats. Orthotopic liver transplantation is the only effective therapy but its application is limited by the scarcity of donor organs. Efforts to replicate his famous Mithridatium made his antidote the most popular and long-lived prescription in history.Īcute liver failure (ALF) is known for extremely high mortality rate, the result of widespread damage of hepatocytes. He made himself immune to normally fatal amounts of arsenic and enjoyed robust health until forced to commit suicide in his 70s. Influenced by traditional theriacs and previous investigators and with access to rich natural resources, Mithridates’ experiments resulted in a formulation of more than 50 ingredients combining animal, plant, and mineral toxins with antidotes. Fearing assassination by poison, he gathered a team of botanists, physicians, and shamans seeking to create a “universal antidote” that would protect him from all poisons. As Rome’s most dangerous enemy until his death in 63 bc, Mithridates is recognized as the first experimental toxicologist for his extensive investigations into a vast number of poisons and antidotes. 134 bc) ruled a Black Sea Empire to rival the Roman Republic in a series of wars that lasted decades.
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