ABSTRACT
ABSTRACT: Background: Statins are drugs used for the treatment of dyslipidemia. However, statins have multiple actions, including anti-inflammatory and immunomodulatory effects, as well as the ability to stimulate new bone formation. Such features could be beneficial for periodontal pathology therapy. Methods: A literature review was conducted using filtered electronic databases (Cochrane and Trip) and unfiltered databases (Medline/PubMed, Scielo and Google Scholar). The articles chosen were controlled and randomized clinical trials that performed local delivery of statins to humans and assessed the effects of immunomodulation and bone regeneration on periodontal disease between 2010 and 2017. All of the studies were blind or double-blind and were written in English. Results: The inclusion criteria were applied to a total of 79 identified articles, and 10 studies were ultimately chosen. The results show that an injected dose of statins or the local delivery of atorvastatin (ATV) leads to a significant improvement in clinical and radiographic periodontal parameters. Moreover, rosuvastatin (RSV) induced stronger beneficial effects when administered systemically, whereas ATV and simvastatin (SMV) had better results following topical delivery. Conclusions: Statins can affect periodontal status, increasing the gain in clinical attachment and decreasing gingival bleeding, probing depth and the magnitude of bone defects. For this reason, statins represent an excellent support measure for conventional periodontal therapy. Specifically, positive effects are seen for local delivery of statins as an adjunct treatment to scaling and root planing (SRP) at doses of 1.2 to 2%. Statins could be administered through topical delivery via direct injection in the periodontal pocket or by brushing with medicated dentifrices. More studies with appropriate designs should evaluate the short and long term clinical benefit of statins inpatients with periodontal pathology. These studies should determine the appropriate dose, timing side effects and ideal vehicles for delivery.
Subject(s)
Humans , Periodontal Diseases , Therapeutics , Bone Regeneration , Hydroxymethylglutaryl-CoA Reductase InhibitorsABSTRACT
Reports indicate that statins (cholesterol-lowering drugs), in addition to lowering cholesterol, have an immunomodulatory effect. This effect may be beneficial for the treatment of several diseases, including periodontal disease. The aim of the present study was to evaluate the immunomodulatory effect of an atorvastatin-medicated dentifrice on CD4+ T cell proliferation. CD4+ T cell proliferation assays and peripheral blood mononuclear cell (PBMC) viability assays were conducted on PBMCs from healthy donors cultured under the following conditions: control, atorvastatin solution, atorvastatin-medicated dentifrice, and dentifrice without atorvastatin at concentrations of 1, 5, 10, 50 and 100 µM. A Generalized Equation Estimation (GEE) model was used to analyze concentration versus proliferation and concentration versus percentage of dead cells within each group evaluated. Atorvastatin-medicated dentifrice (p-value <0.0001) and atorvastatin solution (p-value <0.0001) significantly inhibited CD4+ T cell proliferation in a dose-dependent manner compared with the dentifrice without atorvastatin and control conditions. Only the relationship between atorvastatin solution and percentage of dead cells was significant compared to the other conditions (p-value 0.019). The results revealed that atorvastatin-medicated dentifrice at concentrations of 1 to 100 µM had immunomodulatory effects, inhibiting CD4+ T cell proliferation without affecting PBMC viability. The other components of the dentifrice did not affect CD4+ T cell proliferation or cell viability, indicating its utility as a vehicle to achieve the desired effects of atorvastatin in periodontal tissue. Controlled clinical trials are still needed to evaluate the clinical effects of an atorvastatin-medicated dentifrice on the periodontium.
La literatura indica que las estatinas (medicamentos para bajar el colesterol), además de reducir el colesterol, tienen un efecto inmunomodulador. Este efecto puede ser beneficioso para el tratamiento de varias enfermedades, incluyendo la enfermedad periodontal. El objetivo de este estudio es evaluar el efecto inmunomodulador de una pasta dental medicada con atorvastatina sobre la proliferación celular de linfocitos T CD4+. A partir de células mononucleares de sangre periférica de donantes sanos (PBMC), se realizaron ensayos de proliferación y viabilidad de linfocitos T CD4+ bajo las siguientes condiciones: control, solución de atorvastatina, dentífrico medicado con atorvastatina y dentífrico sin atorvastatina, en concentraciones 1, 5, 10, 50 and 100 µM. Se realizó el análisis estadístico utilizando el modelo Generalized Equation Estimation (GEE) a fin de analizar la concentración versus la proliferación y la concentración versus el porcentaje de muerte celular para cada uno de los grupos. El dentífrico medicado con atorvastatina (valor p <0,0001) y solución de atorvastatina (valor p <0,0001) inhibieron significativamente la proliferación de células T CD4 + de una manera dependiente de la dosis en comparación con el dentífrico sin atorvastatina y condiciones de control. Sólo la relación entre la atorvastatina solución y el porcentaje de células muertas fue significativa en comparación con las otras condiciones (vale-p 0,019). Los resultados revelaron que el dentífrico medicado con atorvastatina en concentraciones de 1 a 100 mM tenía efectos inmunomoduladores, inhibiendo la proliferación de células T CD4 + sin afectar la viabilidad de PBMC. Los otros componentes del dentífrico no afectaron la proliferación de células T CD4 + o la viabilidad celular, indicando su utilidad como vehículo para conseguir los efectos deseados de atorvastatina en el tejido periodontal. Todavía se necesitan ensayos clínicos controlados para evaluar los efectos clínicos de un dentífrico medicado con atorvastatina sobre el periodonto.