Ian C Salveson

Projects

The Mechanism of Acetaminophen Metabolism

Acetaminophen, also known as paracetamol, is a commonly used over-the-counter pain reliever. It is also present in mixtures of prescribed pain medication. Taken in accordance with dosage suggestions, acetaminophen is processed normally by the body and does not cause any adverse side effects; however, taken in excess, acetaminophen can quickly lead to liver failure and death. Acetaminophen alone is responsible for 50% of transplants due to drug related liver injury. Correct identification of the mechanism of acetaminophen induced liver damage is the first step in treating and preventing acetaminophen related liver failure. The currently accepted mechanism for liver injury due to acetaminophen involves the creation of a highly reactive oxidation product NAPQI. However, research has identified the formation of a radical during the enzymatic oxidation of acetaminophen. This has led to a new hypothesis where radicals are continuously forming and combining into polymeric material that would cause a buildup of insoluble material within the liver, preventing blood flow and leading to necrosis. This research will revolve around investigating this new hypothesis by analyzing the products of controlled enzymatic oxidations of acetaminophen using HPLC alongside with NMR and Mass Spectroscopy for the characterization of these products.

Experiments

Flash Chromatography(2/15/2016)

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