Characterization Of The Acute Pancreatitis Induced By Secretory Phospholipases A2 In Rats

Acute pancreatitis (AP) is an inflammatory disease of the pancreas characterized by local inflammation and extrapancreatic effects such as lung injury. Secretory phospholipases A2 (PLA2s) have been implicated in triggering AP, but their exact role to evoke AP is largely unknown. Therefore, we have tested the ability of sPLA2s to induce AP in rats, using venom sPLA2s with residual or high enzymatic activity (bothropstoxin-II and Naja mocambique mocambique venom PLA2, respectively), as well as sPLA2 devoid of catalytic activity (piratoxin-I). The injection of Naja m. mocambique venom PLA2, bothropstoxin-II or piratoxin-I (300 μg/kg each) into the common bile duct increased significantly the pancreatic plasma extravasation and myeloperoxidase activity. The lung myeloperoxidase and serum amylase were also increased for all groups, although the Naja mocambique mocambique venom PLA2 induced higher lung myeloperoxidase and serum amylase values, compared with piratoxin-I and/or bothropstoxin-II. Histopathology of pancreas and lungs in piratoxin-I-injected rats showed interstitial oedema in both tissues, and neutrophil infiltration with acinar cell necrosis in pancreas. In conclusion, sPLA2s induce AP in rats and the catalytic activity is not essential to induce the local effects in pancreas, although it appears to contribute partly to the remote lung injury. © 2005 Elsevier Ltd. All rights reserved.468921926Aho, H.J., Koskensalo, S.M.L., Nevalainen, T.J., Experimental pancreatitis in the rat (1980) Scand. J. Gastroent., 15, pp. 411-416Balsinde, J., Balboa, M.A., Insel, P.A., Dennis, E.A., Regulation and inhibition of phospholipase A2 (1999) Annu. Rev. Pharmacol. 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Characterization of the acute pancreatitis induced by secretory phospholipases A(2) in rats

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOAcute pancreatitis (AP) is an inflammatory disease of the pancreas characterized by local inflammation and extrapancreatic effects such as lung injury. Secretory phospholipases A(2) (PLA(2)s) have been implicated in triggering AP, but their exact role to evoke AP is largely unknown. Therefore, we have tested the ability of sPLA(2)s to induce AP in rats, using venom sPLA(2)s with residual or high enzymatic activity (bothropstoxin-II and Naja mocambique mocambique venom PLA(2), respectively), as well as sPLA(2) devoid of catalytic activity (piratoxin-I). The injection of Naja m. mocambique venom PLA(2), bothropstoxin-II or piratoxin-I (300 mu g/kg each) into the common bile duct increased significantly the pancreatic plasma extravasation and myeloperoxidase activity. The lung myeloperoxidase and serum amylase were also increased for all groups, although the Naja mocambique mocambique venom PLA(2) induced higher lung myeloperoxidase and serum amylase values, compared with piratoxin-I and/or bothropstoxin-II. Histopathology of pancreas and lungs in piratoxin-I-injected rats showed interstitial oedema in both tissues, and neutrophil infiltration with acinar cell necrosis in pancreas. In conclusion, sPLA(2)s induce AP in rats and the catalytic activity is not essential to induce the local effects in pancreas, although it appears to contribute partly to the remote lung injuryPergamon Press468921926FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçãoOxfor

Comparative effect of phoneutria nigriventer spider venom and capsaicin on the rat paw oedema

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCapsaicin, the pungent component of hot peppers, and the venom of the spider Phoneutria nigriventer are able to activate sensory nerves resulting in cutaneous neurogenic plasma extravasation. This study was undertaken to compare the ability of these substances to evoke oedema in the rat hind-paw and mechanisms underlying this effect. Subplantar injection of either Phoneutria nigriventer venom (PNV; 1-100 mug/paw) or capsaicin (10-200 mug/paw) caused a significant paw oedema that was potentiated by CGRP (10 pmol/paw). In rats treated neonatally with capsaicin to deplete neuropeptides. the paw oedema induced by either PNV (100 mug/paw) or capsaicin (100 mug/paw) was partially reduced (P <0.05). The tachykinin NKI receptor antagonist SR140333 (0.2 mu mol/kg; i.v.) prevented the paw oedema induced by the tachykinin NK1 receptor agonist GR73632 (30 pmol/paw) and partially reduced paw oedema induced by PNV or capsaicin. Treatment of rats with compound 48/80 (5 mg/kg; s.c. 3 days) or with both HI receptor antagonist (mepyramine; 1 nmol/paw) and 5-HT receptor antagonist (methysergide; I nmol/paw) significantly inhibited PNV- or capsaicin-induced paw oedema. The combined treatment with mepyramine and methysergide and SR140333 further reduced PNV- and capsaicin-induced paw oedema. The bradykinin B-2 receptor antagonist Hoe 140 affected neither PNV- nor capsaicin-induced responses. Our results suggest that PNV and capsaicin each induce paw oedema that is partially mediated by activation of sensory fibers culminating in the release of substance P as well as by activation of mast cells which in turn release amines such as histamine and 5-HT691315731585FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçã