Inhibition of matrix metalloproteinases in gerbil cholesteatoma: preliminary findings.
OBJECTIVE
This study was conducted to examine the role of matrix metalloproteinases (MMPs) and the impact of a topical MMP inhibitor, ilomostat, on the development of tympanic membrane (TM) atelectasis in the gerbil model.


METHODS
Eustachian tubes were cauterized bilaterally in 19 gerbils. Thereafter, both TMs received once-daily topical treatment for 8 weeks with ilomostat or vehicle or no treatment (n = 6 or 7 per group). TM atelectasis was serially graded, and TMs were harvested at 8 weeks. Gelatin zymograms were performed to determine MMP activity.


RESULTS
The mean activity levels of proenzyme and active MMP-9 and MMP-2 and degree of atelectasis did not differ between groups. TM atelectasis did not correlate to levels of enzymes across individual samples.


CONCLUSIONS
Topical application of an MMP inhibitor did not significantly prevent the development of TM atelectasis. It remains to be determined whether the use of MMP inhibitors may prevent the progression of atelectasis in humans.
Lehman
David A
DA
Department of Otolaryngology, University of Florida, Gainesville 32610-0264, USA.
Wilmoth
Jason G
JG
Prevatt
Angela R
AR
Schultz
Gregory S
GS
Antonelli
Patrick J
PJ
D000818:Animals; D018424:Cholesteatoma, Middle Ear / Q000517:prevention & control*; D004151:Dipeptides / Q000627:therapeutic use*; D005849:Gerbillinae; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D014432:Tympanic Membrane / Q000187:drug effects
D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9