title: Protective effects of sivelestat in a caerulein-induced rat acute pancreatitis model.
abstract: In the present study, we investigated the protective effects of sivelestat on acute pancreatitis (AP) in a rat model. Sivelestat is a specific neutrophil elastase inhibitor, which has been developed in Japan in 1991. Varying doses of sivelestat in normal saline were infused continuously in sivelestat-treated groups through osmotic pumps. Blood and pancreas samples were collected for serological and histopathological studies, and ten rats in each group were taken for survival observation. Increasing doses of sivelestat inhibits the expression of lipase, amylase, corticosterone, IL-1β, TNF-α, and nuclear factor-κB. Furthermore, sivelestat reduces the inflammatory cells infiltration, histological damage, and mortality rate. Meanwhile, the total antioxidant power and serum level of IL-4 in high-dose sivelestat-treated groups were increased. Our findings suggest that the increasing doses of sivelestat protect against caerulein-induced AP in rats, and this protection is possibly associated with the anti-inflammatory ability of sivelestat.
authors.affiliation: General Surgery Department of Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuchang, Wuhan, Hubei, 430071, China, juncaodoctor@yahoo.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Quanyan
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000681:Amylases / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002108:Ceruletide; D003345:Corticosterone / Q000096:biosynthesis; D004195:Disease Models, Animal; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis; D015847:Interleukin-4 / Q000097:blood; D008049:Lipase / Q000096:biosynthesis; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D053491:Proteinase Inhibitory Proteins, Secretory / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013534:Survival; D051996:Transcription Factor RelA / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D053491:Proteinase Inhibitory Proteins, Secretory; C498145:Rela protein, rat; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D002108:Ceruletide; C069195:sivelestat; D008049:Lipase; D000681:Amylases; D005998:Glycine; D003345:Corticosterone