Intravenous antioxidant modulation of end-organ damage in L-arginine-induced experimental acute pancreatitis.
BACKGROUND
Oxidative stress mediates acinar injury in experimental acute pancreatitis (AP) and antioxidants are depleted in human AP. This study tests the hypothesis that exogenous antioxidant supplementation ameliorates experimental AP.


METHODS
Male Sprague-Dawley rats were randomly allocated to 1 of 4 groups (n = 5/group) and sacrificed at 72 h. AP was induced by 250 mg per 100 g body weight of 20% L-arginine hydrochloride in 0.15 mol/l sodium chloride. Group allocations were: group 1 (control) no intervention; group 2 AP; group 3 early multiple antioxidant (MAOX) intervention comprising 15 microg/kg selenium, 30 microg/kg ascorbate and 300 mg/kg N-acetylcysteine given at 6 and 30 h and group 4 the MAOX combination above given at 24 and 48 h. Endpoints were: serum amylase, antioxidant levels, bronchoalveolar lavage (BAL) protein and lung myeloperoxidase (MPO) activity and histological assessment of pancreatic injury.


RESULTS
L-arginine induced AP characterised by oedema, neutrophil infiltration, acinar cell degranulation and elevated serum amylase. Early MAOX reduced pulmonary MPO and BAL protein and reduced acinar swelling, degranulation and pancreatic parenchymal infiltration by inflammatory cells. These features were absent when intervention was delayed.


CONCLUSIONS
In this model, early but not late antioxidant intervention ameliorates pancreatic and pulmonary injury.
Hardman
J
J
Department of Academic Surgery, Cork University Hospital and National University of Ireland, Cork, Ireland.
Shields
C
C
Schofield
D
D
McMahon
R
R
Redmond
H P
HP
Siriwardena
A K
AK
D000111:Acetylcysteine / Q000627:therapeutic use; D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001120:Arginine; D001205:Ascorbic Acid / Q000097:blood / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors
D000975:Antioxidants; D011506:Proteins; D001120:Arginine; D009195:Peroxidase; D000681:Amylases; D012643:Selenium; D001205:Ascorbic Acid; D000111:Acetylcysteine