Major pathological mechanisms of acute pancreatitis are prevented by N-acetylcysteine.
OBJECTIVE
To analyze the capability of N-acetylcysteine (NAC) to prevent major intra-acinar pathogenic mechanisms involved in the development of acute pancreatitis (AP).


METHODS
AP was induced by pancreatic duct obstruction (PDO) in rats. Some animals received NAC (50 mg/kg) 1 h before and 1 h after PDO. During a 24-hour period of PDO, plasma amylase activity and pancreatic glutathione and malondialdehyde levels were measured. Cytosolic Ca(2+) levels and enzyme (amylase and trypsinogen) load in acinar cells were also analyzed by flow cytometry, and histological analysis of the pancreas was performed by electron microscopy.


RESULTS
NAC avoided glutathione depletion at early AP stages, thereby preventing pancreatic oxidative damage, as reflected by normal malondialdehyde levels. By limiting oxidative stress, NAC treatment effectively prevented the impairment of Ca(2+) homeostasis found in acinar cells from early AP onwards, thus protecting the pancreas from damage. In addition, lower quantities of digestive enzymes were accumulated within acinar cells. This finding, together with the significantly lower hyperamylasemia observed in these animals, suggests that NAC treatment palliates the exocytosis blockade induced by PDO.


CONCLUSIONS
By preventing oxidative stress at early AP stages, NAC administration prevents other pathological mechanisms of AP from being developed inside acinar cells, thus palliating the severity of disease.
Sevillano
S
S
Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain.
De la Mano
A M
AM
De Dios
I
I
Ramudo
L
L
Manso
M A
MA
D000111:Acetylcysteine / Q000494:pharmacology*; D000208:Acute Disease; D000818:Animals; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D018384:Oxidative Stress; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010195:Pancreatitis / Q000473:pathology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D000111:Acetylcysteine