The efficacy of combining feG and galantide in mild caerulein-induced acute pancreatitis in mice.
We have previously shown that galantide ameliorates mild acute pancreatitis (AP), and the salivary tripeptide analogue, feG, ameliorates severe AP in mice. In this study, we compared the efficacy of combining galantide and feG with that of the individual agents in treating mild AP induced in mice with 7-hourly caerulein injections. Galantide was co-administered with each caerulein injection commencing with the first injection. feG was co-administered with the first injection of caerulein as a single intraperitoneal injection. Combination of the agents was also administered. Control animals received galantide, feG, or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma enzyme activities were measured. Galantide significantly reduced AP-induced hyperenzymemia by 41-49%. The combination of galantide and feG significantly reduced AP-induced hyperenzymemia by 39-40%, whereas feG alone was without effect. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide, feG, and their combination significantly reduced MPO activity by 83, 44 and 74% respectively, and % abnormal acinar cells by 32, 29 and 36% respectively. This study demonstrates for the first time the beneficial effect of feG in mild caerulein-induced AP. Moreover the data indicate that the hyperenzymemia in mild caerulein-induced AP at 12h possibly reflect a larger secretory component as compared to enzyme release due to neutrophil-mediated acinar cell damage. The effects of the treatment with both peptides indicate a possible role for galantide in modulating neutrophil chemotaxis/activation and supports the hypothesis that galantide may influence neurogenic inflammation in AP.
Barreto
Savio G
SG
Department of General and Digestive Surgery, Flinders Medical Centre and Flinders University, Bedford Park, Adelaide 5042, South Australia, Australia.
Carati
Colin J
CJ
Schloithe
Ann C
AC
Mathison
Ronald
R
Davison
Joseph S
JS
Toouli
James
J
Saccone
Gino T P
GT
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide; D004359:Drug Therapy, Combination; D019004:Galanin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008049:Lipase / Q000097:blood; D051379:Mice; D009842:Oligopeptides / Q000627:therapeutic use*; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013237:Stereoisomerism; D013373:Substance P / Q000031:analogs & derivatives* / Q000627:therapeutic use
D009842:Oligopeptides; C114891:tripeptide FEG; C074975:galantide; D013373:Substance P; D019004:Galanin; D002108:Ceruletide; D008049:Lipase; D000681:Amylases