Calcium and reactive oxygen species in acute pancreatitis: friend or foe?

Acute pancreatitis (AP) is a debilitating and, at times, lethal inflammatory disease, the causes and progression of which are incompletely understood. Disruption of Ca(2+) homeostasis in response to precipitants of AP leads to loss of mitochondrial integrity and cellular necrosis.

While oxidative stress has been implicated as a major player in the pathogenesis of this disease, its precise roles remain to be defined. Recent developments are challenging the perception of reactive oxygen species (ROS) as nonspecific cytotoxic agents, suggesting that ROS promote apoptosis that may play a vital protective role in cellular stress since necrosis is avoided.

Fresh clinical findings have indicated that antioxidant treatment does not ameliorate AP and may actually worsen the outcome. This review explores the complex links between cellular Ca(2+) signaling and the intracellular redox environment, with particular relevance to AP.

Recent publications have underlined the importance of both Ca(2+) and ROS within the pathogenesis of AP, particularly in the determination of cell fate. Future research should elucidate the subtle interplay between Ca(2+) and redox mechanisms that operate to modulate mitochondrial function, with a view to devising strategies for the preservation of organellar function.