In Vivo Analysis of Necrosis and Ferroptosis in Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic steatohepatitis (NASH) is a metabolic liver disease that progresses from simple steatosis to the disease states such as chronic inflammation and fibrosis. In most liver diseases, immunological responses caused by tissue damages or viral infection contribute to the pathological advances, and various types of cell death have been reported to be implicated in their pathogenesis. However, the conventional detection of necrosis in vivo is not currently available, whereas the detection method for apoptosis has been relatively well-established. We recently reported a method for the in vivo detection of necrotic cells in liver disease models by an intravenous injection of Propidium Iodide (PI) into mice. We also provide standard methods for the evaluation of lipid accumulation and fibrosis characteristic of NASH. In addition, by utilizing these procedures and a murine model of steatohepatitis, we showed that ferroptosis, a type of regulated necrotic cell death, could be involved in the pathogenesis of NASH. These approaches allow us to explore the pathophysiological roles of cell death in liver diseases.