Phenytoin Modulates Connective Tissue Metabolism and Cell Proliferation in Human Skin Fibroblast Cultures

Moy, Lawrence S.; Tan, Elaine M.L.; Holness, Ronald; Uitto, Jouni

doi:10.1001/archderm.1985.01660010083024

Cited by 38 publications

(10 citation statements)

References 27 publications

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“…Hence a detailed description of the molecular mechanism of action induced by phenytoin at the skin is limited and most literature on this topic dates back to more than two decades ago [65]. Phenytoin increases selectively the proliferation of fibroblasts, but not of other cell types, in vitro [66,67], but an indirect control of fibroblast proliferation through the release of cytokines from keratinocytes has also been suggested [68]. Phenytoin stimulates the formation of granulation tissue, reduces collagenase activity, and promotes collagen production and deposition thus causing enhanced strength of the wounded area [69].…”

Section: Phenytoinmentioning

confidence: 99%

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

et al. 2020

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Chronic wounds often occur in patients with diabetes mellitus due to the impairment of wound healing. This has negative consequences for both the patient and the medical system and considering the growing prevalence of diabetes, it will be a significant medical, social, and economic burden in the near future. Hence, the need for therapeutic alternatives to the current available treatments that, although various, do not guarantee a rapid and definite reparative process, appears necessary. We here analyzed current treatments for wound healing, but mainly focused the attention on few classes of drugs that are already in the market with different indications, but that have shown in preclinical and few clinical trials the potentiality to be used in the treatment of impaired wound healing. In particular, repurposing of the antiglycemic agents dipeptidylpeptidase 4 (DPP4) inhibitors and metformin, but also, statins and phenyotin have been analyzed. All show encouraging results in the treatment of chronic wounds, but additional, well designed studies are needed to allow these drugs access to the clinics in the therapy of impaired wound healing.

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Section: Phenytoinmentioning

confidence: 99%

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

et al. 2020

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“…An alternate explanation is that a population of fibroblasts consists of functionally distinct cells, and only certain subgroups may be responsive to phenytoin. 59 Moy et al 43 discovered that the effect of phenytoin on human skin fibroblasts is both concentration-and timedependent. At low phenytoin concentrations (5 mg/L) and short incubation times (3 h), phenytoin markedly enhanced cell proliferation.…”

Section: Potential Mechanisms Of Acrionmentioning

confidence: 99%

Phenytoin in Wound Healing

Anstead¹,

Hart²,

Sunahara³

et al. 1996

Ann Pharmacother

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“…Direct evidence for the rapid degradation of newly synthesized collagen as a regulatory mechanism is provided by studies of rabbit lung explants (Bienkowski et al 1978). Human skin fibroblast cultures treated with phenytoin exhibit a marked decrease in the synthesis of collagenase, an enzyme participating in the degradation of collagen (Moy et al 1985). Simpson & Mailman (1981) indicated that human gingival fibroblasts synthesize a collagenase inhibitor.…”

Section: Discussionmentioning

confidence: 99%

The effects of phenytoin (5, 5‐diphenylhydantoin) on human gingival fibroblasts in culture

Vernillo

Schwartz

1987

J of Periodontal Research

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Macromolecular biosynthesis in monolayer cultures of normal and responder human gingival fibroblasts derived from tissue explants was evaluated in the presence or absence of phenytoin (5μg/ml) from the 5th to the 8th day after plating and a labeling period with 14C‐proline (0.2 μCi/ml) for the last 48 hours. Collagenase digestion and hydroxyproline determinations indicated an increase in collagen product. At least part of the increase may have been due to a drug‐modulated decrease in collagen degradation. Phenytoin (PHT) also stimulated synthesis of glycosaminoglycan as indicated by an approximately 2‐fold increase in sulfate‐labeled product. Ultrastructural examination revealed a pronounced change in the protein synthetic apparatus of PHT‐treated cells. Tritiated phenytoin bound to fibroblasts and appeared to undergo internalization as indicated by trypsin treatment.

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Phenytoin Modulates Connective Tissue Metabolism and Cell Proliferation in Human Skin Fibroblast Cultures

Cited by 38 publications

References 27 publications

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

Phenytoin in Wound Healing

The effects of phenytoin (5, 5‐diphenylhydantoin) on human gingival fibroblasts in culture

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