The Possible Potential Therapeutic Targets for Drug Induced Gingival Overgrowth

Abstract

Gingival overgrowth is a side effect of certain medications. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin, the least fibrotic lesions are caused by cyclosporin A, and the intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, activated gingival fibroblasts synthesize and remodel newly created extracellular matrix. Proteins such as transforming growth factor (TGF), endothelin-1 (ET-1), angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to the development of gingival fibrosis. Since inflammation is the prerequisite for gingival overgrowth, mast cells and its protease enzymes also play a vital role in the pathogenesis of gingival fibrosis. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGF-β, CTGF, IGF, PDGF, ET-1, Ang II, and mast cell chymase and tryptase enzymes to fibroblast activation in gingival fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of drug-induced gingival overgrowth.

Fiatalkori hydantion terápia okozta ínyfibrózis kombinált parodontális sebészi-ortodonciai kezelése - Esetismertetés és irodalmi összefoglalás

“…Ugyanakkor sok közlemény megerősíti, hogy a há rom gyógyszercsalád molekulái direkt módon is fokoz zák a gingivális fibroblastok aktivitását és kollagéntermelését [8,17,51]. A Ca-antagonista által fokozott fibroblast aktivitásban több gyulladásos cytokin IL-6, IL-8, IL-1beta, transforming growth factor-β (TGFβ), fibroblast growth factor (FGF) platelet-derived growth factor (PDGF) és connective tissue growth factor (CTGF), valamint a PGE 2 expressziója fokozódott [40,49,54,60]. A három gyógyszercsalád bizonyos mértékben eltérő citokin expressziót produkál.…”

Sequential Platelet-Derived Growth Factor–Simvastatin Release Promotes Dentoalveolar Regeneration

“…40,41 Inflammatory responses appeared to be suppressed and cellular viabilities were increased by the incorporation of PDGF or simvastatin. 12 On the other hand, the higher and persistent PDGF expression may inhibit osteogenesis and even cause the fibrotic gingival hyperplasia, 27,42 whereas myopathy, glucose intolerance, and impaired renal function are the main concerns of taking simvastatin. 43,44 The therapeutic efficiency and the adverse effects of the dosage regimen of the microspheres are still yet to be confirmed.…”

Periodontics Perspective in Identification and Age Estimation

“…Gingival enlargements are quite common and can be classified as focal and diffuse enlargements. The etiology of the gingival enlargement may be inflammatory (abscess), idiopathic (hereditary gingival fibromatosis), drug induced (calcium channel blocker, phenytoin, cyclosporine), granulomatous disease (tuberculosis), neoplasms (leukemia) and any other systemic and local pathology [17][18][19][20][21].…”