ERK and p38 activation are central mediators of irinotecan-induced steatohepatitis

Preoperative chemotherapy for hepatic resection of colorectal liver metastases is associated with the development of chemotherapy-associated steatohepatitis (CASH) which increases the risk of perioperative morbidity and mortality. The aim of this study was to unravel the molecular mechanisms of this phenomenon. Methods and Results: Initially, we determined the dose-range in which irinotecan treatment did not affect the viability of hepatoma cells and primary human hepatocytes. In this dose-range (up to 50µM), irinotecan dose-dependently induced lipid accumulation and pro-inflammatory gene expression. Furthermore…