The Influence of a load of L-arginine on serum amino acids and pancreatic apoptosis/proliferation and ATP levels in the rat.
OBJECTIVE
Administration of high doses of amino acids like ethionine, methionine, and arginine causes pancreatic tissue damage. The initial mechanism behind these effects is not known. The aim of this study was to show the early effects of a load of L-arginine on programed cell death/proliferation and ATP levels in the pancreas.


METHODS
We analyzed in rats the effects of intraperitoneal administration of L-arginine on serum amino acids, pancreatic cell apoptosis/proliferation, and ATP levels at 8, 16, and 24 hours. Serum amino acid concentrations were measured with HPLC, tissue ATP was measured fluorometrically, apoptosis was studied with caspase-3 activity and histone-associated DNA-fragments, and proliferation was studied with thymidine autoradiography.


RESULTS
After a load of l-arginine, there were initially increased serum levels of L-arginine and L-citrulline, but these fell below control levels after 24 hours as well as amino acids in the glutamate family (ornithine, proline, histidine, and glutamine). Initially, increased ATP levels in the pancreatic tissue returned to control levels at 24 hours. The acinar cells proliferation was suppressed and the apoptosis rate strongly increased at 16 and 24 hours. Pancreatic histology showed vacuole formation in the acinar cells at 8 hours. At 16 hours, there was less vacuolization, but apoptotic bodies were seen, and at 24 hours there was cell degeneration but no necrosis.


CONCLUSIONS
After a load of l-arginine, amino acid metabolism causes a high ATP production in the pancreatic tissue that may cause mitochondrial initiation of cell death.
Trulsson
Lena
L
Department of Biomedicine and Surgery, Faculty of Health Sciences, University Hospital, Linköping, Sweden. lena.trulsson@ibk.liu.se
Sandström
Per
P
Sundqvist
Tommy
T
Smeds
Staffan
S
Gasslander
Thomas
T
Svanvik
Joar
J
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000596:Amino Acids / Q000097:blood*; D000681:Amylases / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002956:Citrulline / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D008297:Male; D008938:Mitosis / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014867:Water / Q000032:analysis
D000596:Amino Acids; D011506:Proteins; D014867:Water; D002956:Citrulline; D000255:Adenosine Triphosphate; D004247:DNA; D001120:Arginine; D000681:Amylases