Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro

R. M. Moore, F. Schatz, D. Kumar, B. M. Mercer, A. Abdelrahim, N. Rangaswamy, C. Bartel, J. M. Mansour, C. J. Lockwood, J. J. Moore

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Abstract

Cytokine-mediated inflammation and abruption-induced thrombin generation are separately implicated in matrix metalloproteinase (MMP)-mediated weakening of fetal membranes (FM) leading to preterm premature rupture of the fetal membranes (PPROM). At term, FM of both labored vaginal and unlabored Cesarean deliveries exhibit a weak zone overlying the cervix exhibiting ECM remodeling characterized by increased MMP9 protein and activity. We have reproduced these biochemical changes as well as FM weakening in vitro using tumor necrosis factor-alpha (TNF) and interleukin (IL)-1β, inflammatory cytokines implicated in PPROM. Additionally, we have reported that the antioxidant and NFκB inhibitor alpha-lipoic Acid (LA) blocks these TNF-induced effects. We now present the first direct evidence that thrombin also can induce FM weakening in vitro, and LA treatment inhibits this thrombin-induced-weakening. Full thickness FM fragments from unlabored Cesarean deliveries were incubated with increasing doses of thrombin (0-100 u/ml) for 48 h. Fragments were then strength tested (breaking force and work to rupture) using our published methodology. MMP3 and 9 levels in tissue extracts were determined by Western blot and densitometry. To determine the effect of LA, FM fragments were incubated with control medium or 10 u/ml thrombin, with or without 0.25 mM LA. Strength testing and MMP induction were determined. Thrombin induced a dose-dependent decrease in FM strength (42% baseline rupture force and 45% work to rupture) coupled with a dose-dependent increase in MMP3 and 9 expression (all p < 0.001). Treatment of FM with 0.25 mM LA completely inhibited thrombin-induced FM weakening and MMP expression (all p < 0.001). Thrombin treatment of cultured FM induces mechanical weakening and increased MMP3 and 9. Treatment of FM with LA inhibits these thrombin-induced effects. We speculate LA may prove clinically useful in prevention of PPROM associated with abruption.

Original languageEnglish (US)
Pages (from-to)886-892
Number of pages7
JournalPlacenta
Volume31
Issue number10
DOIs
StatePublished - Oct 2010

Fingerprint

Extraembryonic Membranes
Thioctic Acid
Thrombin
Premature Rupture Fetal Membranes
Matrix Metalloproteinases
Rupture
In Vitro Techniques
Tumor Necrosis Factor-alpha
Cytokines
Tissue Extracts
Densitometry
Interleukin-1
Cervix Uteri
Antioxidants
Western Blotting

Keywords

  • Abruption
  • Biomechanics
  • Fetal membranes
  • Lipoic acid
  • MMP3
  • MMP9
  • Thrombin

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Developmental Biology

Cite this

Moore, R. M., Schatz, F., Kumar, D., Mercer, B. M., Abdelrahim, A., Rangaswamy, N., ... Moore, J. J. (2010). Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro. Placenta, 31(10), 886-892. https://doi.org/10.1016/j.placenta.2010.07.012

Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro. / Moore, R. M.; Schatz, F.; Kumar, D.; Mercer, B. M.; Abdelrahim, A.; Rangaswamy, N.; Bartel, C.; Mansour, J. M.; Lockwood, C. J.; Moore, J. J.

In: Placenta, Vol. 31, No. 10, 10.2010, p. 886-892.

Research output: Contribution to journalArticle

Moore, RM, Schatz, F, Kumar, D, Mercer, BM, Abdelrahim, A, Rangaswamy, N, Bartel, C, Mansour, JM, Lockwood, CJ & Moore, JJ 2010, 'Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro', Placenta, vol. 31, no. 10, pp. 886-892. https://doi.org/10.1016/j.placenta.2010.07.012
Moore RM, Schatz F, Kumar D, Mercer BM, Abdelrahim A, Rangaswamy N et al. Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro. Placenta. 2010 Oct;31(10):886-892. https://doi.org/10.1016/j.placenta.2010.07.012
Moore, R. M. ; Schatz, F. ; Kumar, D. ; Mercer, B. M. ; Abdelrahim, A. ; Rangaswamy, N. ; Bartel, C. ; Mansour, J. M. ; Lockwood, C. J. ; Moore, J. J. / Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro. In: Placenta. 2010 ; Vol. 31, No. 10. pp. 886-892.
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