Ethanol administration delays recovery from acute pancreatitis induced by exocrine hyperstimulation.
Alcohol consumption causes acute alcohol pancreatitis and worsens the prognosis; however, there is no useful model for elucidation of the mechanism underlying this worsening. The aim of our study was to establish a new prognostic model of acute alcohol pancreatitis in rats. To ascertain the effect of continuous infusion of ethanol on each phase, i.e., progression and recovery, in caerulein-induced pancreatic injury in rats, we infused a physiological or supramaximal dose of caerulein intravenously to conscious Wistar rats for up to 6 h (time: 0-6 h) with or without ethanol infusion for 9 h (time: 3-12 h). Ethanol did not induce the pancreatic injury alone or when combined with a physiological dose of caerulein. In the progression phase, ethanol infusion for 3 h (time: 6 h) did not aggravate the pancreatic injury induced by a supramaximal dose of caerulein in terms of plasma amylase and lipase activities but did increase the pancreatic calcium level. In the recovery phase, however, ethanol infusion for 9 h (time: 12 h) significantly restrained the recovery from pancreatic injury as monitored in terms of these activities. Further, ethanol infusion for 9 h significantly increased the cumulative urinary excretion of amylase from 12 to 27 h but did not do the same from 0 to 12 h. In the histological evaluation at 27 h, the induction of acinar cell vacuolization and dilation of the glandular lumina and ducts were significant in the caerulein plus ethanol-treated group. Our findings suggest that ethanol administration delays the recovery rather than worsens the progression in acute pancreatic injury induced by exocrine hyperstimulation, and we consider our experimental model to be a useful tool for studying the pathogenesis of worsening prognosis in acute alcohol pancreatitis.
Yuasa
C
C
Pharmacology Research Laboratory, R&D Headquarters Tokushima Research Center, Taiho Pharmaceutical Co., LTD., Japan.
Irimura
K
K
Oka
T
T
D000208:Acute Disease; D000681:Amylases / Q000652:urine; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D002108:Ceruletide / Q000097:blood / Q000494:pharmacology; D018450:Disease Progression; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D008049:Lipase / Q000097:blood; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D019512:Pancreatitis, Alcoholic / Q000097:blood / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D002492:Central Nervous System Depressants; D000431:Ethanol; D002108:Ceruletide; D008049:Lipase; D000681:Amylases; D002118:Calcium