Acute pancreatitis (AP) is a severe and frequently lethal disorder, but the precise mechanisms are not well understood and there is lack of effective drugs. Therefore, our study examined the in vivo intervention effects of genistein and elucidated its mechanism in acute experimental pancreatitis models. We used cerulein or taurocholate to induce acute pancreatitis (AP) in Sprague-Dawley rats with prior genistein treatment. Histological examination of the pancreas was performed and the expression of unfolded protein response (UPR) components and apoptotic mediators like caspase 12 and c-Jun N-terminal protein kinase (JNK) were measured. The amount of apoptosis in pancreatic acinar cells was also determined. Our studies found that the severity of cerulein- or taurocholate-induced AP was rescued by prior genistein treatment. Genistein stimulated the activation of multiple endoplasmic reticulum (ER) stress-related regulators like GRP78, PERK, eIF2 alpha, and upregulated the expression of the apoptotic genes, caspase 12 and CHOP. Moreover, TUNEL assays showed that genistein treatment promoted acinar cell apoptosis. Taken together, we speculated that ER stress-associated apoptotic pathways in AP are induced by genistein, which showed cytoprotective capacity in the exocrine pancreas. These data suggest novel therapeutic strategies that employ genistein in the prevention of AP. (C) 2018 Elsevier Inc. All rights reserved.
[1]Fudan Univ, Huadong Hosp, Shanghai Inst Geriatr, Shanghai 200040, Peoples R China;
[2]Fudan Univ, Zhongshan Hosp, Dept Pulm Med, Shanghai 200030, Peoples R China;
[3]Pregnancy Res Ctr, Dept Maternal Fetal Med, Parkville, Vic 3052, Australia;
[4]Univ Melbourne, Dept Obstet & Gynaecol, Royal Womens Hosp, Parkville, Vic 3052, Australia;
[5]Fudan Univ, Huadong Hosp, Dept Gastroenterol, Shanghai 200040, Peoples R China;
[6]Fudan Univ, Huadong Hosp, Dept Emergency Med, Shanghai 200040, Peoples R China
(8.0+极速模式)