Octreotide negates the benefit of galantide when used in the treatment of caerulein-induced acute pancreatitis in mice.
BACKGROUND
We have previously shown that galantide, a non-specific galanin receptor antagonist, ameliorates acute pancreatitis (AP) induced in mice. Octreotide, a somatostatin analogue, has been used in the treatment of AP with inconsistent outcomes. This study set out to compare the efficacy of a combined treatment of galantide and octreotide with the efficacy of each agent individually in experimental AP.


METHODS
Acute pancreatitis was induced in mice with 7-hourly caerulein injections. Galantide and/or octreotide were co-administered with each caerulein injection commencing with the first injection. Control animals received galantide, octreotide or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma amylase and lipase activities were measured.


RESULTS
Galantide significantly reduced AP-induced hyperenzymaemia by 39-45%. Octreotide alone, or in combination with galantide, did not significantly alter AP-induced hyperenzymaemia. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide and octreotide administered individually reduced MPO activity by 79% and 50%, respectively; however their combination was without effect. Galantide, octreotide and their combination significantly reduced the percentage of abnormal acinar cells by 28-45%.


CONCLUSIONS
Treatment with galantide alone ameliorated most of the indices of AP studied, whereas treatment with octreotide reduced pancreatic MPO activity and acinar cell damage. Combining the two peptides appears to negate their individual benefits, which suggests an interaction in their mechanism of action.
Barreto
Savio G
SG
Department of General and Digestive Surgery, Flinders Medical Centre, Flinders University, Adelaide, SA, Australia.
Carati
Colin J
CJ
Schloithe
Ann C
AC
Toouli
James
J
Saccone
Gino T P
GT
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002108:Ceruletide; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D019004:Galanin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008049:Lipase / Q000097:blood; D008297:Male; D051379:Mice; D015282:Octreotide / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D015415:Biomarkers; C074975:galantide; D013373:Substance P; D019004:Galanin; D002108:Ceruletide; D009195:Peroxidase; D008049:Lipase; D000681:Amylases; D015282:Octreotide