EXOGENOUS SECRETORY PHOSPHOLIPASES A2 INDUCE EXPERIMENTAL ACUTE PANCREATITIS AND LUNG INJURY IN RATS. EFFECT OF CROTAPOTIN ON THE ACUTE PANCREATITIS INDUCED BY CAERULEIN

LANDUCCI, E.C.T.(2), CAMARGO, E(1),  ESQUISATTO, L.C.M.(1), DE NUCCI, G.(1), ANTUNES, E.(1)

(1)Department of Pharmacology, UNICAMP, (2)Departament of Biochemistry, UNICAMP.

Introduction: Phospholipases A₂ (PLA₂) are important mediators in the acute pancreatitis (AP) and consequent lung injury. We have investigated the AP induced by exogenous PLA₂ from Naja naja venom and the PLA₂ homologue Piratoxin I (a toxin from B.pirajai venom) and the effect of crotapotin (a non-toxic and non-enzymatic acid polypeptide naturally complexed with PLA₂ in the venom of Crotalus durrissus terrificus) on AP induced by caerulein. Methods: Acute pancreatitis was induced by two methods: (1) the i.v. infusion of caerulein (a cholecystocinin analogue, 5 µg/kg/h, 1 mL/h) or PLA₂ from Naja naja venom (30 µg/kg/h, 1 mL/h) for 4 h, (2) the injection into the pancreatobiliary duct of sodium taurocholate 5%, PLA₂ from Naja naja venom or Piratoxin I (100 and 300 mg/kg) in a steady manual pressure over a period of 60 sec. Plasma protein extravasation was measured by ¹²⁵I-human serum albumin. Crotapotin was concomitant infused with caerulein at the doses of 100 and 200 µg/rat. Neutrophil infiltration was assessed by evaluation of the MPO activity in the rat lung tissues. Results: PLA₂ from Naja naja venom did not cause a pancreatic plasma extravasation when infused i.v., although promoted elevated levels of neutrophil infiltration in rat lungs. Both PLA₂ from Naja naja venom and Piratoxin I when injected into the pancreatobiliary duct induced significantly pancreatic plasma extravasation when compared with saline group, but only the higher dose of both substances was able to evoke significant neutrophil infiltration in rat lung. Crotapotin was able to reduces the pancreatic plasma extravasation and the sPLA₂ activity. Conclusions: When infused intravenously PLA₂ from Naja naja venom may be inactivated by pancreatic juice, but when injected into the pancreatobiliary duct either PLA₂s used are able to induce pancreatic plasma extravasation and lung neutrophil infiltration, confirming the key role of PLA₂s in this disease. The inhibitory effect of crotapotin on AP induced by caerulein suggesting that the crotapotin interacts with binding to PLA₂ inespecific sites.

Financial support: FAPESP and CNPq

CORRESPONDENCE TO:

Elen Cristina Teizem Landucci Avenida José Bonifácio, 1351, apto. 14B, Campinas, SP, CEP: 13093-240, Brasil E-mail: landucci@bestway.com.br