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Objectives: The aim was to determine whether premixed calcium silicate-based root canal sealers have better biological properties than AH Plus. Materials and Methods: Searches of studies published up to January 2023 were performed in the PubMed/MEDLINE and EMBASE and via other methods (databases of the International Endodontic Journal, Journal of Endodontics, and gray literature). The inclusion criteria were in vivo animal and in vitro studies that analyzed the response in the dorsal subcutaneous tissue of rats, cell viability, and genotoxicity. Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias (RoB) tool for in vivo studies and modified CONSORT checklist for in vitro were appraised. Meta-analysis was performed using the Stata. Results: Fifty-two studies were included. In the RoB, in vivo studies fulfilled 20%-50% of the items and in vitro 60%-100%. The studies included in the meta-analysis demonstrated better histocompatibility with the premixed calcium silicate-based sealers at 30 days and greater cell viability with these sealers when used in undiluted extracts in experimental period of 72 h and in extracts with 1:2 and 1:4 dilution in 24 and 72 h. In contrast, no difference between materials was found concerning genotoxicity. Conclusion: Premixed calcium silicate-based root canal sealers have better histocompatibility and are less cytotoxic than the epoxy resin-based sealer AH Plus, demonstrating favorable biological behavior.
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The aim of this work was to evaluate the toxicological action of AH Plus (AHP), Bio-C Sealer (BCS), and EndoSequence BC Sealer (ESB), using Drosophila melanogaster as the model organism performing in vivo and ex vivo analysis. D. melanogaster were exposed for 10 days to three concentrations (5 mg/ml, 10 mg/ml, and 20 mg/ml) of AHP, BCS, and ESB sealers mixed with 10 ml of standard diet. During this period, the mortality of flies was evaluated. On the 11th day, the locomotor activity test was performed and the flies were euthanized for oxidative damage analysis (reactive species and lipid peroxidation) and cell viability (resazurin reduction). For the mortality curves evaluation, the log-rank test (Mantel-Cox) was used. For the analysis of other data, a one-way analysis of variance (ANOVA) was applied, followed by Tukey's post hoc test (α = 0.05). Regarding mortality, there were no significant differences. The locomotor activity was reduced, mainly in the two highest concentrations of AHP and BCS. Besides, reactive species generation was bigger in the AHP 20 mg/ml group. AHP induced a lipid peroxidation increase in all three concentrations tested, when compared to other sealers. Considering cell viability, the two highest concentrations of AHP reduced this parameter; while in other sealers, viability was reduced only in the highest concentration. AHP showed changes in oxidative markers that led to greater damage to the flies.
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OBJECTIVES: The present study aimed to determine in silico toxicity predictions of test compounds from hydraulic calcium silicate-based sealers (HCSBS) and AH Plus and computationally simulate the interaction between these substances and mediators of periapical inflammation via molecular docking. MATERIALS AND METHODS: All chemical information of the test compounds was obtained from the PubChem site. Predictions for bioavailability and toxicity analyses were determined by the Molinspiration Cheminformatics, pkCSM, ProTox-II and OSIRIS Property Explorer platforms. Molecular docking was performed using the Autodock4 AMDock v.1.5.2 program to analyse interactions between proteins (IL-1ß, IL-6, IL-8, IL-10 and TNF-α) and ligands (calcium silicate hydrate, zirconium oxide, bisphenol-A epoxy resin, dibenzylamine, iron oxide and calcium tungstate) to establish the affinity and bonding mode between systems. RESULTS: Bisphenol-A epoxy resin had the lowest maximum dose tolerated in humans and was the test compound with the largest number of toxicological properties (hepatotoxicity, carcinogenicity and irritant). All systems had favourable molecular docking. However, the ligands bisphenol-A epoxy resin and dibenzylamine had the greatest affinity with the cytokines tested. CONCLUSION: In silico predictions and molecular docking pointed the higher toxicity and greater interaction with mediators of periapical inflammation of the main test compounds from AH Plus compared to those from HCSBS. CLINICAL RELEVANCE: This is the first in silico study involving endodontic materials and may serve as the basis for further research that can generate more data, producing knowledge on the interference of each chemical compound in the composition of different root canal sealers.
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Compostos Benzidrílicos , Benzilaminas , Compostos de Cálcio , Resinas Epóxi , Fenóis , Materiais Restauradores do Canal Radicular , Silicatos , Humanos , Resinas Epóxi/toxicidade , Simulação de Acoplamento Molecular , Inflamação , Materiais Restauradores do Canal Radicular/toxicidadeRESUMO
Diabetes mellitus (DM) and arterial hypertension are considered serious public health problems. Several studies have shown that oxidative stress is usually related to the onset of DM and hypertension, as well their associated complications. Moreover, the levels of some minerals are closely related to the pathophysiology of these diseases. Thus, in this study we aimed to evaluate the effect of metformin on the redox profile and mineral levels in the serum of patients with DM type 2 and hypertension. We also tested the effect of metformin on the viability and redox profile of peripheral blood mononuclear cells (PBMCs) for 24 h. As expected, we found that patients with type 2 DM and hypertension + type 2 DM had higher fasting glucose and triglyceride levels. As groundbreaking research, we found that both patients DM type 2 and Hypertension + DM type 2 had reduced myeloperoxidase (MPO) activity. On the other hand, the levels of total thiols (PSH) and vitamin C were increased. There was no statistical significance for the alterations in mineral levels. In addition, metformin treatment had no cytotoxic effect on PBMCs. Similarly, in patients of both groups, MPO activity was reduced and PSH levels were increased in PBMCs. We have shown that metformin is a drug with a protective effect in patients with DM type 2 against oxidative stress by reducing MPO activity and improving the levels of PSH and antioxidant defenders such as vitamin C. The results of in vitro assays support the antioxidant effect of metformin. Furthermore, we suggest studies to assess the biochemical mechanisms of metformin and how it can be used in a pharmacological therapeutic perspective against oxidative damage.
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Antioxidantes/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Estudos Transversais , Leucócitos Mononucleares , Biomarcadores , Minerais , Ácido Ascórbico/uso terapêuticoRESUMO
This study evaluated the biocompatibility of degradable polydioxanone (PDS) electrospun drug delivery systems (hereafter referred as matrices) containing metronidazole (MET) or ciprofloxacin (CIP) after subcutaneous implantation in rats. Sixty adult male rats were randomized into six groups: SHAM (sham surgery); PDS (antibiotic-free matrix); 1MET (one 25 wt% MET matrix); 1CIP (one 25 wt% CIP matrix); 2MET (two 25 wt% MET matrices); and 2CIP (two 25 wt% CIP matrices). At 3 and 30 days, animals were assessed for inflammatory cell response (ICR), collagen fibers degradation, and oxidative profile (reactive oxygen species [ROS]; lipid peroxidation [LP]; and protein carbonyl [PC]). At 3 days, percentages of no/discrete ICR were 100, 93.3, 86.7, 76.7, 50, and 66.6 for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP, respectively. At 30 days, percentages of no/discrete ICR were 100% for SHAM, PDS, 1MET, and 1CIP and 93.3% for 2MET and 2CIP. Between 3 and 30 days, SHAM, 1CIP, and 2CIP produced collagen, while 1MET and 2MET were unchanged. At 30 days, the collagen fiber means percentages for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP were 63.7, 60.7, 56.6, 62.6, 51.8, and 61.7, respectively. Antibiotic-eluting matrices showed similar or better oxidative behavior when compared to PDS, except for CIP-eluting matrices, which showed higher levels of PC compared to SHAM or PDS at 30 days. Collectively, our findings indicate that antibiotic-eluting matrices may be an attractive biocompatible drug delivery system to fight periodontopathogens. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2019.
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Antibacterianos/química , Materiais Biocompatíveis/química , Ciprofloxacina/química , Metronidazol/química , Nanocápsulas/química , Nanofibras/química , Polidioxanona/química , Animais , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Liberação Controlada de Fármacos , Humanos , Masculino , Metronidazol/farmacologia , Oxirredução , Implantação de Prótese , Ratos , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo , Engenharia Tecidual , Alicerces TeciduaisRESUMO
Amphetamine (AMPH) abuse is a serious public health problem due to the high addictive potential of this drug, whose use is related to severe brain neurotoxicity and memory impairments. So far, therapies for psychostimulant addiction have had limited efficacy. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have shown beneficial influences on the prevention and treatment of several diseases that affect the central nervous system. Here, we assessed the influence of fish oil (FO), which is rich in n-3 PUFA, on withdrawal and relapse symptoms following re-exposure to AMPH. Male Wistar rats received d,l-AMPH or vehicle in the conditioned place preference (CPP) paradigm for 14 days. Then, half of each experimental group was treated with FO (3 g/kg, p.o.) for 14 days. Subsequently, animals were re-exposed to AMPH-CPP for three additional days, in order to assess relapse behavior. Our findings have evidenced that FO prevented relapse induced by AMPH reconditioning. While FO prevented AMPH-induced oxidative damages in the prefrontal cortex, molecular assays allowed us to observe that it was also able to modulate dopaminergic cascade markers (DAT, TH, VMAT-2, D1R and D2R) in the same brain area, thus preventing AMPH-induced molecular changes. To the most of our knowledge, this is the first study to show a natural alternative tool which is able to prevent psychostimulant relapse following drug withdrawal. This non-invasive and healthy nutraceutical may be considered as an adjuvant treatment in detoxification clinics.
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Anfetamina/toxicidade , Ácidos Graxos Ômega-3/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Animais , Condicionamento Clássico/efeitos dos fármacos , Ácidos Graxos/metabolismo , Óleos de Peixe/farmacologia , Masculino , Córtex Pré-Frontal/metabolismo , Carbonilação Proteica , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Comportamento Espacial/efeitos dos fármacosRESUMO
Drug abuse and addiction are overwhelming health problems mainly during adolescence. Based on a previous study of our research group, the rats that received modafinil (MD) during the adolescence showed less preference for amphetamine (AMPH) in adulthood. Our current hypothesis is that MD will show beneficial effects against AMPH preference and abstinence symptoms during adolescence, a critical lifetime period when drug hedonic effects are more pronounced. We investigated the influence of MD pretreatment on AMPH preference in conditioned place preference (CPP) paradigm in adolescent rats and anxiety-like symptoms during drug withdrawal (48â¯h after the last AMPH dose) in elevated plus maze (EPM) task. Besides that, oxidative and molecular status were evaluated in the ventral tegmental area (VTA) and striatum. Our findings showed, as it was expected, that adolescent animals developed AMPH preference together with anxiety-like symptoms during the drug withdrawal while the MD pretreatment prevented those behaviors. Besides promoting benefits on reward parameters, MD was able to preserve VTA and striatum from oxidative damages. This was observed by the increased catalase activity and reduced generation of reactive species and lipid peroxidation, which were inversely modified by AMPH exposure. At molecular level, MD exerted an interesting modulatory activity on the VTA and induced an up-regulation in striatal dopaminergic targets (TH, DAT, D1R and D2R). So far, during the adolescence, MD presented beneficial behavioral outcomes that could be attributed to its modulatory activity on the striatal dopaminergic system in an attempt to maintain the adequate dopamine levels.
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Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Ansiedade/prevenção & controle , Estimulantes do Sistema Nervoso Central/farmacologia , Modafinila/farmacologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Anfetamina/farmacologia , Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Animais , Ansiedade/etiologia , Ansiedade/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/crescimento & desenvolvimento , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Masculino , Ratos Wistar , Maturidade Sexual , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/psicologia , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/crescimento & desenvolvimento , Área Tegmentar Ventral/metabolismoRESUMO
ABSTRACT Tooth losses due to pathological processes continue to be a reality in daily clinical dentistry, inducing functional and psychological complications in patients. In view of this, a new option for the management of this problem - tissue engineering - has been studied in Dentistry. This field, considered multidisciplinary, uses three key elements for tissue regeneration: scaffolds (extracellular matrices) - natural or synthetic; cells, and growth factors. In this sense, combination of these three elements may induce regeneration of the dental pulp, bone and periodontal tissue, among others. Therefore, the aim of this study was to conduct a literature review, describing the main elements of tissue engineering and their applicability in Dentistry, as a means of updating dental surgeons about this subject.
RESUMO As perdas dentárias, devido aos processos patológicos, ainda são uma realidade na clínica odontológica diária, induzindo complicações funcionais e psicológicas ao paciente. Diante disso, uma nova opção para o manejo desse problema vem sendo estudada na Odontologia, a engenharia tecidual. Essa área, considerada multidisciplinar, utiliza três elementos chaves para a regeneração dos tecidos: os scaffolds (matriz extracelular) naturais ou sintéticos, as células e os fatores de crescimento. Nesse sentido, a combinação desses três elementos pode induzir a regeneração da polpa dentária, tecido ósseo e periodontal, entre outros. Portanto, o objetivo deste estudo é realizar uma revisão da literatura, descrevendo e atualizando os cirurgiões-dentistas sobre os principais elementos da engenharia tecidual e sua aplicabilidade na Odontologia.
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Haloperidol is a widely used antipsychotic, despite the severe motor side effects associated with its chronic use. This study was carried out to compare oral dyskinesia induced by different formulations of haloperidol-loaded nanocapsules containing caprylic/capric triglycerides, fish oil or grape seed oil (GSO) as core, as well as free haloperidol. Haloperidol-loaded lipid-core nanocapsules formulations were prepared, physicochemical characterized and administered (0.5 mg kg-1-ip) to rats for 28 days. Oral dyskinesia was evaluated acutely and subchronically and after that cell viability and free radical generation in cortex and substantia nigra. All formulations presented satisfactory physicochemical parameters. Acutely, all formulations were able to prevent oral dyskinesia development in comparison to free haloperidol, except haloperidol-loaded nanocapsules containing GSO, whose effect was only partial. After subchronic treatment, all haloperidol-loaded nanocapsules formulations prevented oral dyskinesia in relation to free drug. Also, haloperidol-loaded nanocapsules containing fish oil and GSO were more effective than caprylic/capric triglycerides nanocapsules and free haloperidol in cell viability preservation and control of free radical generation. Our findings showed that fish oil formulation may be considered as the best formulation of haloperidol-loaded lipid-core nanocapsules, being able to prevent motor side effects associated with chronic use of antipsychotic drugs, as haloperidol.
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Antidiscinéticos/farmacologia , Discinesias/tratamento farmacológico , Óleos de Peixe/química , Haloperidol/farmacologia , Nanocápsulas/uso terapêutico , Óleos de Plantas/química , Vitis/química , Animais , Produtos Biológicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Discinesias/metabolismo , Peixes , Masculino , Ratos WistarRESUMO
Addiction is a serious health problem which leads to general social impairment. The period of adolescence plays a significant role in drug abuse liability. Psychostimulants, such as modafinil (MOD), are majorly used by teenagers seeking improvements in cognition, which contributes to its indiscriminate use. This study aimed to investigate the influence of MOD (64 mg/kg by gavage, once a day) treatment during adolescence [post-natal day (PND) 28-42] on amphetamine (AMPH, 4 mg/kg i.p.)-conditioned place preference (CPP) in early adulthood (PND 60). Our findings showed that AMPH increased CPP for the drug and anxiety-like behaviours; on the other hand, AMPH decreased the number of crossings and recognition index. In addition, AMPH decreased catalase activity and increased reactive species, malondialdehyde and carbonyl protein levels in the hippocampus. AMPH also increased pro-brain derived neurotrophic factor (BDNF), tyrosine kinase receptor B, dopamine transporter, D1R and decreased BDNF and D2R immunoreactivity. Contrarily, animals pre-exposed to MOD showed reduced AMPH-CPP, no locomotor impairment, less anxiety-like behaviours and no memory deficits. In addition, MOD showed antioxidant activity by preventing AMPH-induced oxidative damage in the hippocampus. Moreover, molecular analysis showed that MOD was able to modulate the hippocampal dopaminergic system, thus preventing AMPH-induced impairments. Animals that received MOD during adolescence showed reduced AMPH-CPP in early adulthood. These unexpected behavioural effects of MOD on CPP could be due to its hippocampal dopaminergic system modulation, mainly by its action on D1R, which is closely linked to drug addiction. Nevertheless, further studies are necessary.