In vitro response of human gingival epithelioid S-G cells to minocycline

H. Babich, David Tipton

Research output: Contribution to journalArticle

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Abstract

Minocycline, a broad-spectrum antibiotic used in the treatment of acne and periodontal disease and to control inflammatory diseases such as rheumatoid arthritis, has recently been shown to induce a spectrum of adverse health effects. In the light of these contradictory data, this research was directed to provide basic information on the toxicology of minocycline, using in vitro cell culture models, and to evaluate its efficacy in periodontal therapies, particularly for wound healing. The human gingival epithelioid S-G cell line was used as the bioindicator. The greater toxicity of minocycline over doxycycline and tetracycline, related antimicrobial agents, probably correlated with its higher lipophilicity. The cytotoxicity of minocycline was unaffected by an S9 hepatic microsomal fraction, indicating that it is a direct-acting, rather than a metabolism-mediated, cytotoxicant. In comparative toxicity studies, much variation in the degree of sensitivity to minocycline was noted for different cell types. No correlation in the extent of sensitivity to minocycline and the physiologic state of the bioindicator cell (normal, transformed or malignant) was noted. The toxicity of minocycline to the S-G cells was dependent on its concentration and length of exposure. For a continuous 3-day exposure of the S-G cells to minocycline, the midpoint cytotoxicity (or, NR50) value, as quantified in the neutral red (NR) assay, was 204 μg/ml on day 1, 84 μg/ml on day 2, and 59 μg/ml on day 3. For a 1-h exposure of the S-G cells in phosphate buffered saline (PBS), the NR50 value was 780 μg/ml minocycline. Although a 1-h exposure in PBS to 200 μg/ml minocycline exerted some toxicity, the S-G cells recovered on exposure to growth medium; irreversible, progressive damage occurred at 400 μg/ml minocycline and greater. Minocycline, at 50 μg/ml, enhanced attachment of the S-G cells to a gelatin-coated surface and cell migration towards an immobilized fibronectin gradient, both biologic parameters important in periodontal wound healing. Minocycline generally had little or no effect on production of the pro-inflammatory cytokines, interleukin-6 (IL-6) and interleukin-8 (IL-8), by non-activated S-G cells, the exception being stimulation of IL-6 at 48 h. IL-1β, however, greatly stimulated IL-6 and IL-8 production, which was further increased by concurrent exposure to minocycline. This suggested that minocycline may enhance the ability of gingival epithelial cells to participate in the early, inflammatory phase of periodontal wound healing. The limitation of minocycline efficacy to a rather narrow window of concentration, centering about 50 μg/ml, and primarily for short-term exposures may possibly explain, in part, the contradictory clinical data on the health effects of this drug.

Original languageEnglish (US)
Pages (from-to)11-21
Number of pages11
JournalToxicology in Vitro
Volume16
Issue number1
DOIs
StatePublished - Feb 11 2002

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Gastrin-Secreting Cells
Minocycline
Toxicity
Wound Healing
Interleukin-6
In Vitro Techniques
Biomarkers
Cytotoxicity
Interleukin-8
Phosphates
Health
Disease control
Neutral Red
Doxycycline
Acne Vulgaris
Periodontal Diseases
Gelatin
Anti-Infective Agents
Tetracycline

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

In vitro response of human gingival epithelioid S-G cells to minocycline. / Babich, H.; Tipton, David.

In: Toxicology in Vitro, Vol. 16, No. 1, 11.02.2002, p. 11-21.

Research output: Contribution to journalArticle

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