N-acetylcysteine prevents intra-acinar oxygen free radical production in pancreatic duct obstruction-induced acute pancreatitis

Abstract

Although oxygen free radicals (OFR) are considered to be one of the pathophysiological mechanisms involved in acute pancreatitis (AP), the contribution of acinar cells to their production is not well established. The aim of the present study was to determine the effect of N-acetylcysteine (NAC) in the course of AP induced by pancreatic duct obstruction (PDO) in rats, directly analysing by flow cytometry the quantity of OFR generated in acinar cells. NAC (50 mg/kg) was administered 1 h before and 1 h after PDO. Measurements by flow cytometry of OFR generated in acinar cells were taken at different PDO times over 24 h, using dihydrorhodamine-123 as fluorescent dye. Histological studies of pancreas and measurements of neutrophil infiltration in the pancreas, pancreatic glutathione (GSH), malondialdehyde (MDA) levels, plasma amylase activity and hemoconcentration were carried out in order to assess the severity of AP at different stages. NAC effectively blunted GSH depletion at early AP stages and prevented OFR generation found in acinar cells as a consequence of AP induced by PDO. This attenuation of the redox state impairment reduced cellular oxidative damage, as reflected by less severe pancreatic lesions, normal pancreatic MDA levels, as well as diminished neutrophil infiltration in pancreas. Hyperamylasemia and hemoconcentration following AP induction were ameliorated by NAC administration at early stages, when oxidative stress seems to be critical in the development of pancreatitis. In conclusion, NAC reinforces the antioxidant defences in acinar cells, preventing OFR generation therefore attenuating oxidative damage and subsequently reducing the severity of PDO-induced AP at early stages of the disease.

Organophosphorus Insecticides and Glucose Homeostasis

“…The precise mechanisms underlying OPI-induced pancreatitis are still undefined, although it is believed to involve obstruction of pancreatic ducts and /or enhanced reactive oxygen species (Dressel et al, 1982;Sevillano et al, 2003, Sultatos, 1994. Involvement of oxidative stress following acute exposure to OPI has been reported recently (Banerjee et al, 2001) and it has been demonstrated unequivocally that lipid peroxidation is one of the molecular mechanisms involved in OPI-induced cytotoxicity (Akhgari et al, 2003;Ranjbar et al, 2002;Abdollahi et al, 2004b).…”

Beneficial Effect of N-Acetylcysteine against Organophosphate Toxicity in Mice

“…15) Its antioxidant action is believed to originate from its ability to stimulate reduced glutathione (GSH) synthesis, therefore maintaining intracellular GSH levels and scavenging ROS. 16) NAC is used clinically to treat several diseases related to oxidative stress and/or GSH deficiency such as paracetamol (acetaminophen) overdose, VIH infection, and lung and heart diseases.…”

Effect of N-acetylcysteine on neutrophil functions during experimental acute pancreatitis

“…In the literature, majority of studies used male rats, [3,4,6,7,13,14,19] some both male and female rats without sex discrimination, [12] and finally some studies used only female rats. [21,22] In this study, we used female rats.…”

“…It has been investigated as an antioxidant compound in various experimental studies. [7,8] Various antioxidants have no useful effects in taurocholate-induced pancreatitis, but NAC was found to be beneficial. Therefore, OFR formation may be an important factor in taurocholate-induced pancreatitis.…”