Efeito de resinas experimentais contendo inibidores de proteases da matriz sobre gelatinases e colagenases / Effect of experimental resins containing protease inhibitors on gelatinases and collagenase

A evolução das resinas compostas fez com que esses materiais passassem a ter uma durabilidade maior e características estéticas muito boas, mas o risco de cárie recorrente é ainda um problema a ser resolvido. Na tentativa de solucionar esse problema, estudos vêm sendo conduzidos na tentativa de se formularem resinas compostas contendo agentes antibacterianos, como é o caso da incorporação de clorexidina (CHX). Outro fato que impede a longevidade deste material é a degradação de matriz de colágeno por proteases ativadas por pH ácido. Para tentar contornar esse problema, a adição de clorexidina, assim como Epigallocatechin gallate (EGCg), clássicos antibacterianos e inibidores de proteases da matriz , como as metaloproteinases da matriz (MMP) a resinas, poderia melhorar a eficácia destes materiais como substitutos de dentina em procedimentos restauradores, aumentando a longevidade do tratamento restaurador, mediante preservação das propriedades mecânicas do material. Assim, o objetivo desse estudo é avaliar o poder de inibição de resinas experimentais contendo inibidores conhecidos de proteases da matriz sobre gelatinases e colagenase. Para isso, copolímeros experimentais foram preparados combinando Bis-GMA com o diluente TEGDMA (70/30 mol%). Com exceção do copolímero placebo (sem drogas), EGCg ou CHX foram incorporados a 1% em peso isoladamente ou em combinação, a 0,5% em peso cada. Amostras contendo EGCg, CHX ou EGCg e CHX concentradas 10X foram obtidas do armazenamento de espécimes polimerizados da resina experimental em água deionizada (1 mL) após o período de 24h a 37°C e sua posterior concentração. O efeito da ação dos inibidores foi checado por zimografia e confirmado por um ensaio enzimático específico para colagenases e gelatinases. Os dados passaram por teste de homogeneidade (Bartlett) e normalidade (Kolmogorov-Smirnov) e foram avaliados por ANOVA a 2 critérios, seguido pelo teste de Bonferroni para comparações individuais (p<0,05). Os resultados...

The evolution of composite resins made these materials to have a greater durability and very good esthetics characteristics, but the risk of recurrent caries is still a problem to be solved. In the attempt to solve this problem, studies are being conducted with the purpose to formulate composite resins containing antibacterial agents, such as chlorhexidine (CHX). Another fact that prevents the longevity of this material is the degradation of the collagen matrix by the proteases activated by acidic pH. In order to solve this problem, the addition of chlorhexidine and/or Epigallocatechin gallate (EGCg), classical antibacterial agents and inhibitors of matrix proteases, such as matrix metalloproteinases (MMP) in resins, could improve the efficacy of these materials as dentin substitutes in restorative procedures, increasing the longevity of the restorative treatment, while preserving the mechanical properties of the material. Thus, the aim of this study is to evaluate the ability of experimental resins containing known matrix protease inhibitors on the inhibition of gelatinases and collagenase. For this purpose, experimental copolymers were prepared combining Bis-GMA with the diluent TEGDMA (70/30 mol%). Except for the placebo copolymer (drug free), EGCg or CHX were incorporated at 1% in weight, isolated or in combination (0.5% in weight each). Samples containing EGCg, CHX or EGCg and CHX concentrated 10X were obtained after storage of polymerized specimens of the experimental resin in deionized water (1 mL) after the period of 24 h, at 37°C and after that were concentra. The effect of the action of the inhibitors was checked by zymography and confirmed by an enzymatic test specific for collagenases and gelatinases. The data passed in the tests of homogeneity (Bartlett test) and normality (Kolmogorov-Smirnov test), and were evaluated by 2-way ANOVA, followed by Bonferroni test for individual comparisons (p<0.05). The results of this study showed that the...

Tissue inhibitor of metalloproteinases-4. The road less traveled.

Tissue inhibitors of metalloproteinases (TIMPs) regulate diverse processes, including extracellular matrix (ECM) remodeling, and growth factors and their receptors' activities through the inhibition of matrix metalloproteinases (MMPs). Recent evidence has shown that this family of four members (TIMP-1 to TIMP-4) can also control other important processes, such as proliferation and apoptosis, by a mechanism independent of their MMP inhibitory actions. Of these inhibitors, the most recently identified and least studied is TIMP-4. Initially cloned in human and, later, in mouse, TIMP-4 expression is restricted to heart, kidney, pancreas, colon, testes, brain and adipose tissue. This restricted expression suggests specific and different physiological functions. The present review summarizes the information available for this protein and also provides a putative structural model in order to propose potential relevant directions toward solving its function and role in diseases such as cancer.

The role of matrix metalloproteinases in the oral environment.

This review focuses specifically on matrix metalloproteinases (MMPs) and their role in physiological and pathological extracellular matrix (ECM) remodeling and degradation processes in the oral environment. A group of enzymes capable of degrading almost all ECM proteins, MMPs contribute to both normal and pathological tissue remodeling. The expression of different MMPs may be upregulated in pathological conditions such as inflammation and tumor invasion. The balance between activated MMPs and tissue inhibitors of metalloproteinases (TIMPs) controls the extent of ECM remodeling. Prior to mineralization, MMPs may participate in the organization of enamel and dentin organic matrix, or they may regulate mineralization by controlling the proteoglycan turnover. There is evidence indicating that MMPs could be involved in the etiology of enamel fluorosis and amelogenesis imperfecta. They seem to play a part in dentinal caries progression, since they have a crucial role in dentin collagen breakdown in caries lesions. MMPs have been identified in pulpal and periapical inflammation and are strongly correlated with periodontal diseases, since they are the major players in collagen breakdown during periodontal tissue destruction. The use of MMP inhibitors could help the prevention and treatment of many MMP-related oral diseases.