Significance of apoptotic cell death in systemic complications with severe acute pancreatitis

Abstract

In severe acute pancreatitis, multiple organ failure in the early stage after onset, and sepsis in the late stage, due to infection of pancreatic or peripancreatic devitalized tissue, contribute to its high mortality. In analogy with sepsis, evidence has accumulated of the significance of apoptotic cell death in the systemic manifestations associated with acute pancreatitis. Since we identified apoptosis-inducing activity in pancreatitis-associated ascitic fluid in 1995, a number of investigators, including our group, have reported, through animal experiments, that apoptosis occurred in the parenchymal cells constituting organs, such as alveolar epithelial cells in the lung, renal tubular cells in the kidney, and hepatocytes in the liver, and this apoptosis was involved in organ dysfunction with severe acute pancreatitis. Moreover, through clinical and experimental investigations, apoptosis has been revealed to be involved in the mechanism of infectious complications in acute pancreatitis. Namely, apoptosis in lymphatic tissues and peripherally circulating lymphocytes is involved in the impairment of cellular immunity, and apoptosis in gut epithelial cells is implicated in bacterial translocation. These results suggest that apoptotic cell death may play a considerable role in affecting mortality and morbidity in severe acute pancreatitis. Control of apoptosis could be a potent strategy for improvement of the clinical outcome in severe acute pancreatitis.

Inhibition of acinar apoptosis occurs during acute pancreatitis in the human homologue ΔF508 cystic fibrosis mouse

“…For example, nonpancreatic organ injury/dysfunction in AP is primarily due to apoptotic rather than necrotic epithelial cell death (74) and may be accentuated by administration of an apoptosis inducer. Hence, strategies to reduce the severity of AP by inhibiting necrosis and enhancing apoptosis may require selective targeting of pancreatic rather than nonpancreatic tissues.…”

Cell Death and DAMPs in Acute Pancreatitis

“…Caspases not only mediate apoptosis but also protect cells against necrosis by cleavage and inactivation of PARP or trypsin (55). Perhaps paradoxically, intracellular heat shock proteins (HSPs) protect pancreatic acinar cells partly by inhibition of apoptosis (56,57), suggesting a pathogenic role of apoptosis in AP (58). Subsequently, researchers also observed that pancreatic acinar cells undergoing apoptosis can release histones, DNA and HMGB1, which facilitate pancreatic injury and the inflammatory response (10,11).…”

Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis

“…There is a kind of substantial distinction between apoptosis and necrosis (Samuilov et al, 2000). The extent of apoptosis is associated with SAP-induced multiple organ injury (Takeyama, 2005;Zhang et al, 2007c). Salvia miltiorrhiza ('Danshen' in Chinese) injection and dexamethasone injection are representative traditional Chinese and Western medicines, respectively, most frequently used for the treatment of SAP patients.…”

“…These compounds can protect endothelial cells, and prevent inflammation, lipid peroxidation, and calcium overload (Kim et al, 2005;Li et al, 2006;Ding and Yuan, 2007;Lam et al, 2007;Zhao et al, 2008). Studies have proved that Salvia miltiorrhiza can mitigate the pathological changes in the liver, lung, kidney, intestine, and stomach of SAP rats, and prevent the occurrence of multiple organ failure (Zhang et al, 2002a;2002b;2002c;2005). Dexamethasone has anti-inflammatory, anti-toxic, and anti-shock effects.…”