Effect of IS-741 (a new synthetic antiinflammatory agent) on acute necrotizing pancreatitis in dogs

Shuji Isaji, Jitsuo Hayashi, Takashi Higashiguchi, Hajime Yokoi, Yoshifumi Ogura, Takashi Noguchi, Yoshifumi Kawarada

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

IS-741, a new synthetic anti-inflammatory agent, is known to have some inhibitory effect on cytosolic phospholipase A2 (cPLA2), an enzyme which hydrolyzes cellular phospholipids, liberating fatty acids and lysophospholipids and providing the precursor substrates for the biosynthesis of eicosanoids and platelet-activating factor. cPLA2 is therefore an attractive target for the development of novel therapies. During infusion of lactated Ringer's solution at a rate of 10 ml/kg/h, acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. The dogs were then divided into two groups: group A (nontreatment), no treatment during the experiment, and group B (IS-741), intravenously injected with IS-741 at 6 and 30 h after induction of acute pancreatitis. As a result, the survival rate was significantly higher in group B than in group A. Mean arterial pressure and PaO2 were well maintained in group B as compared with group A. The NAG index, which is known to be markedly increased in renal tubular damage, was significantly lower in group B than in group A. Histological examination of the pancreas, lung, and kidney in group B showed milder changes than in group A. cPLA2 activity in the pancreas, lung and renal cortex was much lower in group B than in group A, but sPLA2 activity in these tissues did not differ significantly between the two groups. In conclusion, IS-741 exerts a potentially therapeutic effect on experimental acute pancreatitis by mitigating the degree of damage in the pancreas, lung, and kidney. The inhibitory effect of IS-741 on cPLA2 may contribute to one of the antiinflammatory mechanisms of actions of this agent.

Original languageEnglish
Pages (from-to)47-51
Number of pages5
JournalDigestion
Volume60
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 01-01-1999
Externally publishedYes

Fingerprint

Acute Necrotizing Pancreatitis
Cytosolic Phospholipases A2
Anti-Inflammatory Agents
Dogs
Pancreatitis
Kidney
Pancreas
Lung
Lysophospholipids
Eicosanoids
Pancreatic Ducts
Platelet Activating Factor
Therapeutic Uses
Gallbladder
Bile
Phospholipids
Arterial Pressure
Fatty Acids
IS 741
Enzymes

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Isaji, S., Hayashi, J., Higashiguchi, T., Yokoi, H., Ogura, Y., Noguchi, T., & Kawarada, Y. (1999). Effect of IS-741 (a new synthetic antiinflammatory agent) on acute necrotizing pancreatitis in dogs. Digestion, 60(SUPPL. 1), 47-51. https://doi.org/10.1159/000051453
Isaji, Shuji ; Hayashi, Jitsuo ; Higashiguchi, Takashi ; Yokoi, Hajime ; Ogura, Yoshifumi ; Noguchi, Takashi ; Kawarada, Yoshifumi. / Effect of IS-741 (a new synthetic antiinflammatory agent) on acute necrotizing pancreatitis in dogs. In: Digestion. 1999 ; Vol. 60, No. SUPPL. 1. pp. 47-51.
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Isaji, S, Hayashi, J, Higashiguchi, T, Yokoi, H, Ogura, Y, Noguchi, T & Kawarada, Y 1999, 'Effect of IS-741 (a new synthetic antiinflammatory agent) on acute necrotizing pancreatitis in dogs', Digestion, vol. 60, no. SUPPL. 1, pp. 47-51. https://doi.org/10.1159/000051453

Effect of IS-741 (a new synthetic antiinflammatory agent) on acute necrotizing pancreatitis in dogs. / Isaji, Shuji; Hayashi, Jitsuo; Higashiguchi, Takashi; Yokoi, Hajime; Ogura, Yoshifumi; Noguchi, Takashi; Kawarada, Yoshifumi.

In: Digestion, Vol. 60, No. SUPPL. 1, 01.01.1999, p. 47-51.

Research output: Contribution to journalArticle

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T1 - Effect of IS-741 (a new synthetic antiinflammatory agent) on acute necrotizing pancreatitis in dogs

AU - Isaji, Shuji

AU - Hayashi, Jitsuo

AU - Higashiguchi, Takashi

AU - Yokoi, Hajime

AU - Ogura, Yoshifumi

AU - Noguchi, Takashi

AU - Kawarada, Yoshifumi

PY - 1999/1/1

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N2 - IS-741, a new synthetic anti-inflammatory agent, is known to have some inhibitory effect on cytosolic phospholipase A2 (cPLA2), an enzyme which hydrolyzes cellular phospholipids, liberating fatty acids and lysophospholipids and providing the precursor substrates for the biosynthesis of eicosanoids and platelet-activating factor. cPLA2 is therefore an attractive target for the development of novel therapies. During infusion of lactated Ringer's solution at a rate of 10 ml/kg/h, acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. The dogs were then divided into two groups: group A (nontreatment), no treatment during the experiment, and group B (IS-741), intravenously injected with IS-741 at 6 and 30 h after induction of acute pancreatitis. As a result, the survival rate was significantly higher in group B than in group A. Mean arterial pressure and PaO2 were well maintained in group B as compared with group A. The NAG index, which is known to be markedly increased in renal tubular damage, was significantly lower in group B than in group A. Histological examination of the pancreas, lung, and kidney in group B showed milder changes than in group A. cPLA2 activity in the pancreas, lung and renal cortex was much lower in group B than in group A, but sPLA2 activity in these tissues did not differ significantly between the two groups. In conclusion, IS-741 exerts a potentially therapeutic effect on experimental acute pancreatitis by mitigating the degree of damage in the pancreas, lung, and kidney. The inhibitory effect of IS-741 on cPLA2 may contribute to one of the antiinflammatory mechanisms of actions of this agent.

AB - IS-741, a new synthetic anti-inflammatory agent, is known to have some inhibitory effect on cytosolic phospholipase A2 (cPLA2), an enzyme which hydrolyzes cellular phospholipids, liberating fatty acids and lysophospholipids and providing the precursor substrates for the biosynthesis of eicosanoids and platelet-activating factor. cPLA2 is therefore an attractive target for the development of novel therapies. During infusion of lactated Ringer's solution at a rate of 10 ml/kg/h, acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. The dogs were then divided into two groups: group A (nontreatment), no treatment during the experiment, and group B (IS-741), intravenously injected with IS-741 at 6 and 30 h after induction of acute pancreatitis. As a result, the survival rate was significantly higher in group B than in group A. Mean arterial pressure and PaO2 were well maintained in group B as compared with group A. The NAG index, which is known to be markedly increased in renal tubular damage, was significantly lower in group B than in group A. Histological examination of the pancreas, lung, and kidney in group B showed milder changes than in group A. cPLA2 activity in the pancreas, lung and renal cortex was much lower in group B than in group A, but sPLA2 activity in these tissues did not differ significantly between the two groups. In conclusion, IS-741 exerts a potentially therapeutic effect on experimental acute pancreatitis by mitigating the degree of damage in the pancreas, lung, and kidney. The inhibitory effect of IS-741 on cPLA2 may contribute to one of the antiinflammatory mechanisms of actions of this agent.

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