Pancreatic regeneration after chronic ethanol feeding in rats.
Increase of phosphatidic acid (PA) accumulation in response to caerulein (Cae) and after subtotal pancreatectomy (SP) has been previously described and phospholipase D (PLD) derived PA involvement in pancreatic regeneration was suggested. We also described decrease of Cae stimulated PA accumulation after a single dose of ethanol (both in vitro and in vivo). The present study was undertaken in order to determine the influence of chronic ethanol feeding on basal and Cae stimulated PA accumulation and other parameters of pancreatic regeneration in control and ethanol feed rats. Male rats were pair fed ad libitum with an isocaloric liquid diet (Lieber De Carli) with or without ethanol. In vitro study: pair fed rats were killed after 2 or 6 weeks of feeding, pancreata were dissected out and weighted, dispersed pancreatic acini were then prepared and loaded with 3H myristic acid in order to label the phosphatidylcholine pool. Phosphatidic acid (3H PA) accumulation, in the presence of propranolol, was measured after stimulation with increasing doses of Cae. In vivo study: PA was measured 3 days after SP or sham operation in both groups of rats, and also after 1 h of Cae infusion (0.25 microg/kg/h). Pancreatic weight, amylase, protein, RNA and DNA content were established.


RESULTS
In vitro study 1) Basal PLD activity expressed as PA accumulation was significantly elevated after 6 weeks of ethanol feeding in comparison to the control values (28%). 2) Cae in doses ranging from 100 pM to 5 nM was not able to stimulate PA accumulation in isolated pancreatic acini prepared from ethanol fed rats. In vivo study: 1) Body weight and pancreatic weight were similar in, both the ethanol fed and the control groups, after 2 and 6 weeks. 2) Ethanol feeding significantly decreased total amylase content in the pancreas, but did not change protein, RNA and DNA content. 3) in contrast to the control animals in which SP caused a 71.1% increase of PA accumulation over the sham operation, subtotal pancreatectomy was not able to stimulate PA in rats fed with ethanol. 4) Also Cae infusion did not stimulate PA accumulation in the ethanol fed animals in comparison to the controls. Since the involvement of PLD activation in the early stages of pancreatic regeneration was postulated, our results suggest that chronic ethanol feeding can influence this process by decrease of PA production, probably because of the inhibition of hydrolytic PLD activity in the presence of ethanol. This could be one of the mechanisms responsible for pancreatic injury after chronic ethanol consumption.
Rydzewska
G
G
Department of Gastroenterology, University Medical School, Białystok, Poland.
Jurkowska
G
G
Wróblewski
E
E
Faszczewska
A
A
Gabryelewicz
A
A
D000681:Amylases / Q000032:analysis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002108:Ceruletide / Q000494:pharmacology*; D002918:Chymotrypsin / Q000032:analysis; D004247:DNA / Q000032:analysis; D000431:Ethanol / Q000008:administration & dosage*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010180:Pancreatectomy; D010712:Phosphatidic Acids / Q000096:biosynthesis* / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*; D012997:Solvents / Q000008:administration & dosage*
D005765:Gastrointestinal Agents; D010712:Phosphatidic Acids; D011506:Proteins; D012997:Solvents; D000431:Ethanol; D012313:RNA; D002108:Ceruletide; D004247:DNA; D000681:Amylases; D002918:Chymotrypsin