Fig. 2.

Direct action of alcohol on pancreatic acinar cells has varied pathways. Alcohol-related intracellular activation of proteases is caused by disruption of apical secretion as well as increased levels of circulating TNF-α. Disturbed apical secretion of proteases also causes basolateral release of zymogen and its activation in interstitial space. Oxidative metabolism of alcohol leads to mitochondrial dysfunction and subsequent apoptosis. ER dysfunction caused by alcohol increases Ca2⁺ levels and leads to reduction of ATP production in pancreatic acinar cells and subsequently causes further ER damage.