Subject(s)
Antineoplastic Agents/pharmacokinetics , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Micelles , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/blood , Cell Line, Tumor , Cross-Linking Reagents , Disulfides/chemistry , Dithiothreitol/administration & dosage , Dithiothreitol/pharmacokinetics , Doxorubicin/administration & dosage , Doxorubicin/pharmacokinetics , Drug Delivery Systems , Drug Stability , Humans , Hydrogen-Ion Concentration , Lysosomes/metabolism , Magnetic Resonance Spectroscopy , Mice , Mice, Nude , Nanoparticles , Particle Size , Polyethylene Glycols/chemistry , Polymers/chemistry , Spectroscopy, Fourier Transform InfraredABSTRACT
Periradicular lesions are primarily evoked as a response to a bacterial challenge emanating from an infected root canal. Many bacteria such as those of the genera Porphyromonas, Prevotella, and others have been isolated from infected root canals. The cause of periradicular lesions is related to the destruction of the extracellular matrix (ECM). Matrix metalloproteinases (MMPs) such as interstitial collagenase (MMP-1), gelatinase A (MMP-2), gelatinase B (MMP-9), and so on are products of inflammatory cells and, once activated, are intimately involved in the degradation of the ECM. However, there are no reports regarding the destruction of the ECM by bacterial extracts from Prevotella nigrescens (P. nigrescens). The present study was conducted to evaluate the activating effect of a whole-cell extract (WCE) of P. nigrescens on proMMP-2 and proMMP-9. P. nigrescens WCE was mixed with proMMP-2 or proMMP-9 under many conditions, and the activation of these MMPs was determined by gelatin zymography. A band indicating a lower molecular weight of 66 kd or 84 kd, which migrated faster than the band of proMMP-2 (72 kd) or proMMP-9 (92 kd) respectively, was detected, which could be the active form of either MMP. The present study suggests that P. nigrescens might be able to activate proMMP-2 and proMMP-9 in vivo and that this activation might be related to the destruction of periapical tissues.
Subject(s)
Matrix Metalloproteinase 2/physiology , Matrix Metalloproteinase 9/physiology , Prevotella nigrescens/physiology , Cell Line, Tumor , Culture Media, Conditioned/pharmacology , Dithiothreitol/pharmacokinetics , Electrophoresis, Polyacrylamide Gel , Enzyme Activation/drug effects , Enzyme Precursors/drug effects , Extracellular Matrix Proteins/metabolism , Gelatin/metabolism , Gelatinases/drug effects , Humans , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 9/analysis , Matrix Metalloproteinase 9/drug effects , Protease Inhibitors/pharmacologyABSTRACT
The aim of this study was to investigate the possible involvement of the glutamatergic system in the toxicity of organochalcogens, since this is an important neurotransmitter system for signal transduction and neural function. The results indicated that 100 microM diphenyl diselenide (PhSe)(2) and diphenyl ditelluride (PhTe)(2) inhibit by 50 and 70% (P<0.05), respectively, [(3)H]glutamate binding in vitro. Acute administration of 25 micromol/kg (PhSe)(2) or 3 micromol/kg (PhTe)(2) caused a significant reduction in [(3)H]glutamate (30%, P<0.05) or [(3)H]MK-801 binding (30%, P<0.05) to rat synaptic membranes. These results suggest that (PhSe)(2) and (PhTe)(2) affect, in a rather complex way, the glutamatergic system after acute in vivo exposure in rats. In vitro, total [(3)H]GMP-PNP binding was inhibited about 40% at 100 microM (PhSe)(2) and (PhTe)(2). Acute exposure in vivo to (PhSe)(2) decreased the stable [(3)H]GMP-PNP binding to 25% and (PhTe)(2) to 68% of the control value (P<0.05, for both compounds). Simultaneously, the unstable binding of [(3)H]GMP-PNP was decreased about 30 and 50% (P<0.05, for both compounds) after exposure to (PhSe)(2) and (PhTe)(2), respectively. GMP-PNP stimulated adenylate cyclase (AC) activity significantly in control animals. (PhSe)(2)- and (PhTe)(2)-treated animals increased the basal activity of this enzyme, but GMP-PNP stimulation was totally abolished. These results suggest that the toxic effects of organochalcogens could result from action at different levels of neural signal transduction pathways, possibly involving other neurotransmitters besides the glutamatergic system.
