Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates aspirin-induced gastric mucosal injury in rats.
Inhibition of type IV phosphodiesterase (PDE IV) activity reduces the production of various proinflammatory cytokine and suppresses neutrophil activation. Nonsteroidal anti-inflammatory drugs such as aspirin induce gastric mucosal lesions. In the pathogenesis of aspirin-induced gastric mucosal lesion, the contributions, of activated inflammatory cells and proinflammatory cytokine production are critical. The specific PDE IV inhibitor rolipram is known to be a potent inhibitor of inflammation by increasing intracellular cyclic AMP in leukocytes. The aim of the present study was to determine whether rolipram can ameliorate aspirin-induced gastric mucosal lesions in rats and whether the agent can inhibit the inrease in neutrophil accumulation and the production of proinflammatory cytokines. Gastric lesions were produced by administration of aspirin (200 mg/kg) and HCI (0.15 N; 8.0 ml/kg). Rolipram was injected 30 min before aspirin administration. The tissue myeloperoxidase concentration in gastric mucosa was measured as an indicat or of neutrophil infiltration. The gastric mucosal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined by ELISA. The intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. Gastric mucosal lesions induced by aspirin were significantly inhibited by treatment with rolipram. The mucosal myeloperoxidase concentration was also suppressed by rolipram. Increases in the gastric content of TNF-alpha and IL-1beta after aspirin administration were inhibited by pretreatment with rolipram. We demonstrated that the specific type IV PDE inhibitor, rolipram, could have a potent antiulcer effect, presumably mediated by its anti-inflammatory properties.
Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita City, Akita, Japan 010-8543.
Masaru
M
Odashima
Michiro
M
Otaka
Mario
M
Jin
Koga
K
Komatsu
Noriaki
N
Konishi
Isao
I
Wada
Youhei
Y
Horikawa
Tamotsu
T
Matsuhashi
Reina
R
Ohba
Jinko
J
Oyake
Nastumi
N
Hatakeyama
Sumio
S
Watanabe
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D016207:Cytokines / Q000276:immunology; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D005756:Gastritis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000032:analysis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D020889:Rolipram / Q000494:pharmacology / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D010726:Phosphodiesterase Inhibitors; D009195:Peroxidase; D020889:Rolipram; D001241:Aspirin