Protective effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthase in a carrageenan-induced model of local inflammation.
A cytotoxic cycle triggered by oxidant-induced DNA single strand breakage and subsequent activation of the nuclear enzyme poly (ADP-ribose) synthetase have been shown to contribute to the cellular injury during various forms of oxidant stress in vitro. The aim of the present study was to investigate the role of poly (ADP-ribose) synthetase in a model of acute local inflammation (carrageenan-induced pleurisy), where oxyradicals, nitric oxide and peroxynitrite are known to play a crucial role in the inflammatory process. The results show that the poly (ADP-ribose) synthetase inhibitor 3-aminobenzamide (given at 1-30 mg/kg) inhibits the inflammatory response (pleural exudate formation, mononuclear cell infiltration, histological injury). Moreover, 3-aminobenzamide reduces the formation of nitrotyrosine, an indicator of the formation of peroxynitrite, in the lung. The present results demonstrate that 3-aminobenzamide, presumably by inhibition of poly (ADP-ribose) synthetase, exerts potent anti-inflammatory effects. Part of the anti-inflammatory effects of 3-aminobenzamide may be related to a reduction of neutrophil recruitment into the inflammatory site.
Cuzzocrea
S
S
Children's Hospital Medical Center, Division of Critical Care, Cincinnati, OH 45229, USA.
Zingarelli
B
B
Gilad
E
E
Hake
P
P
Salzman
A L
AL
Szabó
C
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002351:Carrageenan; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005122:Exudates and Transudates / Q000187:drug effects / Q000201:enzymology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats
D000893:Anti-Inflammatory Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D002351:Carrageenan; D009195:Peroxidase; D019001:Nitric Oxide Synthase