Marimastat treatment downregulates matrix metalloproteinase (MMP) gene expression and MMP-activities.

<p>Following repeated carbon tetrachloride (CCl4) administration, Marimastat did not affect hepatic transcript levels of MMP-2 (A), or MMP-3 (B) as quantified by real-time RT-PCR. Hepatic MMP-8 (C) and MMP-9 (D) transcripts were significantly upregulated in livers from Marimastat treated animals, whereas hepatic MMP-13 mRNA was significantly higher in the vehicle treated animals (E). Marimastat inhibits interstitial collagenolytic and gelatinolytic activity in a dose-dependent matter (F). Relative gelatinase and interstitial collagenase activities after 4 hours in liver homogenates supplemented with increasing concentrations of Marimastat, as determined by degradation of DQ-gelatin and collagen (black and grey squares, respectively). Oil, non-fibrotic control group; CCl4, fibrotic mice; VEH, vehicle treated control group; MAR, Marimastat treated experimental group; TNF, tumor necrosis factor; MMP, matrix metalloproteinase; *, P<0.05; **, P<0.01; ***, P<0.001 vs. vehicle alone. Data are expressed as means ± standard error and in arbitrary units.