Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca 2+ -Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis

• Published in: BioMed research international Vol. 2016; p. 1736024
• Main Authors: Wang, Gui-Jun, Wang, Yue, Teng, Yong-Sheng, Sun, Fa-Lv, Xiang, Hong, Liu, Jian-Jun, Xia, Shi-Lin, Zhang, Gui-Xin, Chen, Hai-Long, Shang, Dong
• Format: Journal Article
• Language: English
• Published: United States 2016
• Subjects: Acrylates - administration & dosage; Animals; Apoptosis - drug effects; Calcium - metabolism; Calpain - antagonists & inhibitors; Calpain - biosynthesis; Caspase 12 - biosynthesis; Caspase 12 - genetics; Caspase 3 - biosynthesis; Caspase 3 - genetics; Emodin - administration & dosage; Gene Expression Regulation - drug effects; Humans; Inflammation - drug therapy; Inflammation - genetics; Inflammation - pathology; Neutrophils - drug effects; Pancreatitis - drug therapy; Pancreatitis - genetics; Pancreatitis - pathology; Rats; Signal Transduction - drug effects
• ISSN: 2314-6141

Severe acute pancreatitis (SAP) results in high mortality. This is partly because of early multiple organ dysfunction syndromes that are usually caused by systemic inflammatory response syndrome (SIRS). Many studies have reported the beneficial effects of emodin against SAP with SIRS. However, the exact mechanism underlying the effect of emodin remains unclear. This study was designed to explore the protective effects and underlying mechanisms of emodin against SIRS in rats with SAP. In the present study, cytosolic Ca levels, calpain 1 activity, and the expression levels of the active fragments of caspases 12 and 3 decreased in neutrophils from rats with SAP and increased after treatment with emodin. Delayed neutrophil apoptosis occurred in rats with SAP and emodin was able to reverse this delayed apoptosis and inhibit SIRS. The effect of emodin on calpain 1 activity, the expression levels of the active fragments of caspases 12 and 3, neutrophil apoptosis, and SIRS scores were attenuated by PD150606 (an inhibitor of calpain). These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca -calpain 1-caspase 12-caspase 3 signaling pathway.