D. P. Milgrom1, X. Jin2, Y. Jiang1, L. Koniaris1, T. Zimmers1 1Indiana University,Department Of Surgery,Indianapolis, IN, USA 2Thomas Jefferson University,Department Of Surgery,Philadelphia, PA, USA
Introduction: Repair and regeneration in fatty liver is associated with increased hepatocellular injury and increased risk for perioperative mortality. We set out to identify a pharmacologic agent that induces epidermal growth factor receptor (EGFR) and improves hepatic regeneration in the setting of fatty liver and obesity.
Methods: Diet-induced obese mice were injected with resveratrol or DMSO control. After being subjected to 70% hepatectomy they were necropsied and liver samples were evaluated with the use of immunohistochemistry, western blot assay, and liver EchoMRI.
Results: Resveratrol was found to induce liver EGFR mRNA, protein, and phosphorylation of EGFR. Resveratrol increased PCNA levels without increasing liver mass, due to concomitant reduction in hepatic lipid content. Resveratrol did not increase serum ALT, AST, or bilirubin in normal or obese mice. Resveratrol ameliorates liver injury and accelerated regeneration after partial hepatectomy, while reducing macrosteatosis and presence of apoptotic hepatocytes. Resveratrol reduced mortality in obese mice that underwent extended 80% hepatectomy.
Conclusion: Resveratrol increases EGFR expression, decreases hepatic lipid content, and promotes hepatocyte proliferation and recovery after hepatectomy. This indicates that further study into resveratrol and other EGFR restoring therapy is warranted for potential benefit in preventing liver failure and dysfunction in the setting of fatty liver surgery.