Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

Toxicology. 2005 Oct 15;214(1-2):131-9. doi: 10.1016/j.tox.2005.06.023.

Abstract

We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-kappaB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-kappaB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-kappaB, and MPO activities were significantly reduced in 3-AB group at each time point (p<0.05). Plasma MMP-9 increased maximally at 4h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-kappaB increased maximally at 24h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-kappaB and the infiltration of neutrophils in ischemic stroke.

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Benzamides / therapeutic use*
  • Brain / drug effects*
  • Brain / enzymology
  • Brain / metabolism
  • Brain Ischemia / complications*
  • Brain Ischemia / enzymology
  • Disease Models, Animal
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / blood*
  • NF-kappa B / biosynthesis
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Stroke / drug therapy*
  • Stroke / enzymology
  • Stroke / etiology
  • Up-Regulation

Substances

  • Benzamides
  • NF-kappa B
  • Poly(ADP-ribose) Polymerase Inhibitors
  • 3-aminobenzamide
  • Matrix Metalloproteinase 9