Phenytoin and its metabolite, 5-(p-Hydroxyphenyl-), 5-Phenylhydantoin, decrease supernatant levels of matrix-metalloproteases in the human macrophage: implications for drug-induced gingival overgrowth

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  • March 21, 2019
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  • Serra, Ryan J.
    • Affiliation: School of Dentistry, Department of Periodontology
Abstract
  • OBJECTIVES: To evaluate the effects of Phenytoin (PHT) and its metabolite 5-(p- Hydroxyphenyl-), 5-Phenylhydantoin (HPPH) on LPS-induced macrophage expression of MMP, TIMP, TNF-α, and IL-6. METHODS: Human macrophages were pretreated with either: 1) 15μg/ml PHT, 2) 50μg/ml PHT, 3) 15μg/ml HPPH, or 4) 50μg/ml HPPH for 1 hour, then challenged with 100ng/ml A. actinomycetemcomitans (A.a.) LPS. Untreated cells served as control cultures. Total RNA was extracted at 4 hours, and supernatants were collected at 24 hours. RESULTS: A dose-dependent reduction of supernatant A.a.- induced MMP-1, MMP-3, MMP-9, and TIMP-1 was noted upon pretreatment with PHT and HPPH. A minimal effect was noted on gene expression for MMP-9 and TIMP-1. MMP2, MMP12, TIMP2-4 production does not appear to be influenced Aa LPS, PHT, or HPPH. CONCLUSIONS: A.a. LPS-induced macrophage expression of MMP-1, MMP- 3, MMP-9, and TIMP-1 is blunted by exposure to PHT and HPPH.
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  • In Copyright
Advisor
  • Nares, Salvador
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
Date uploaded
  • October 11, 2010

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