Mechanisms of matrix metalloproteinase-9 and matrix metalloproteinase-2 inhibition by N-acetylcysteine in the human term decidua and fetal membranes.
OBJECTIVE
The purpose of this study was to evaluate the effect of N-acetylcysteine on the activity and secretion of the matrix metalloproteinases in the decidua, amnion, and chorion and the secretion of the tissue inhibitor of matrix metalloproteinase-1.


METHODS
Samples from eight nonlaboring women were taken at elective cesarean section and incubated in an in vitro organ culture in the absence or presence of N-acetylcysteine. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activity was measured with the use of gel zymography. Western blot analysis was used to measure matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase-1 secretion. Data were analyzed with the paired Student t test.


RESULTS
N-acetylcysteine had a direct inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of tissue origin, starting at 1.0 mmol/L. In cultured media, 20 mmol/L N-acetylcysteine inhibited matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in all three tissues. A differential response was demonstrated for matrix metalloproteinase-2 secretion, depending on the tissue that was studied. Its secretion was decreased in decidua at 10 mmol/L and 20 mmol/L; in amnion, the secretion was inhibited at 0.1 mmol/L and not affected at all in chorion. Matrix metalloproteinase-9 secretion was not affected in a statistically significant manner in any tissue. In the chorion, matrix metalloproteinase-9 showed a trend toward increased secretion. Tissue inhibitor of matrix metalloproteinase-1 secretion significantly decreased in the decidua at 20 mmol/L.


CONCLUSIONS
N-acetylcysteine, at higher concentrations, has an inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of the tissue origin and the differential effect on secretion depending on the tissue and N-acetylcysteine concentration.
Weiss
Amir
A
Department of Obstetrics and Gynecology, Laboratory for Research in Reproductive Sciences, Ha'Emek Medical Center, Afula 18101, Israel.
Goldman
Shlomit
S
Ben Shlomo
Izhar
I
Eyali
Vered
V
Leibovitz
Shamir
S
Shalev
Eliezer
E
D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D002585:Cesarean Section; D046508:Culture Techniques; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011336:Probability; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000111:Acetylcysteine