Recent Advances in Understanding the Complexity of Alcohol-Induced Pancreatic Dysfunction and Pancreatitis Development
Karuna Rasineni,
Mukund P. Srinivasan,
Appakalai N. Balamurugan,
Bhupendra S. Kaphalia,
Shaogui Wang,
Wen-Xing Ding,
Stephen J. Pandol,
Aurelia Lugea,
Liz Simon,
Patricia E. Molina,
Peter Gao,
Carol A. Casey,
Natalia A. Osna,
Kusum K. Kharbanda
Affiliations
Karuna Rasineni
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Mukund P. Srinivasan
Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555-0419, USA
Appakalai N. Balamurugan
Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Department of Surgery, University of Cincinnati, Cincinnati, OH 45229, USA
Bhupendra S. Kaphalia
Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555-0419, USA
Shaogui Wang
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, MO 66160, USA
Wen-Xing Ding
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, MO 66160, USA
Stephen J. Pandol
Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Aurelia Lugea
Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Liz Simon
Department of Physiology, Louisiana State University Health Sciences Center-New Orleans, New Orleans, LA 70112, USA
Patricia E. Molina
Department of Physiology, Louisiana State University Health Sciences Center-New Orleans, New Orleans, LA 70112, USA
Peter Gao
Program Director, Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-6902, USA
Carol A. Casey
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Natalia A. Osna
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Kusum K. Kharbanda
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Chronic excessive alcohol use is a well-recognized risk factor for pancreatic dysfunction and pancreatitis development. Evidence from in vivo and in vitro studies indicates that the detrimental effects of alcohol on the pancreas are from the direct toxic effects of metabolites and byproducts of ethanol metabolism such as reactive oxygen species. Pancreatic dysfunction and pancreatitis development are now increasingly thought to be multifactorial conditions, where alcohol, genetics, lifestyle, and infectious agents may determine the initiation and course of the disease. In this review, we first highlight the role of nonoxidative ethanol metabolism in the generation and accumulation of fatty acid ethyl esters (FAEEs) that cause multi-organellar dysfunction in the pancreas which ultimately leads to pancreatitis development. Further, we discuss how alcohol-mediated altered autophagy leads to the development of pancreatitis. We also provide insights into how alcohol interactions with other co-morbidities such as smoking or viral infections may negatively affect exocrine and endocrine pancreatic function. Finally, we present potential strategies to ameliorate organellar dysfunction which could attenuate pancreatic dysfunction and pancreatitis severity.
