Inhibition of inducible nitric oxide synthase-derived nitric oxide as a therapeutical target for acute pancreatitis induced by secretory phospholipase A2.

摘要: Background Nitric oxide is a key signalling molecule in the pathogenesis of inflammation, but its role acute pancreatitis and related abdominal pain induced by secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus (Cdt) venom has not been investigated. Methods Male Wistar rats were i.v. injected with L-NAME (20 mg/kg), aminoguanidine (AG, 50 mg/kg), 7-nitroindazole (7-NI, 10 mg/kg) or vehicle 10 min before 60 min after injection sPLA2 (300 μg/kg) into common bile duct. After 4 h injection, hyperalgesia inflammation assessed addition to serum amylase, nitrite/nitrate (NOx), pancreas lipoperoxidation 3-nitrotyrosine (3-NT) contents. Results sPLA2-induced pancreatitis, hyperalgesia, hyperamylasemia increased concentration NOx correlated 3-NT pancreas. Pretreatment all nitric synthase (NOS) inhibitors significantly reduced mechanical only iNOS blockade AG suppressed oedema increase. The therapeutic approach NOS produced similar reduction pattern treatment also inhibited concentrations pancreatic myeloperoxidase. nNOS 7-NI myeloperoxidase activity both lung. Conclusions Therapeutic provides benefits terms inhibition pancreatitis-related while ameliorates inflammatory cell influx reduces resultant levels, thus representing alternative pharmacological strategies for clinical associated PLA2.