Apical Periodontitis Group Research Articles

Apical periodontitis as an aggravating factor for the severity of rheumatoid arthritis: An animal study.

The present study investigated the influence of apical periodontitis (AP) on the severity of rheumatoid arthritis (RA) using a Wistar rat model. Forty male Wistar rats were distributed across four groups (n = 10) based on the induction of RA and AP: Control, RA, AP, and RA + AP. RA was induced through two immunisations with type II collagen emulsified in incomplete Freund's adjuvant, followed by one immunisation with complete Freund's adjuvant. After 21 days of RA induction, AP was induced by exposing the pulp of four molars. Animals were euthanized after 28 days of pulp exposure. Through the experiment, visual and behavioural assessments tracked RA development and the knees and hind paw joints were measured. Micro-computed tomography scans of knees and hind paws, as well as mandibles and maxillae, were conducted to evaluate RA severity and the presence of AP, respectively. Serum samples were collected to analyse proinflammatory cytokines (IL-1β, IL-2, IL-17, and TNF-α). Non-parametric data were analysed using the Kruskal-Wallis test followed by Student-Newman-Keuls test, while one-way anova followed by Tukey's test was performed for parametric data. A significance level of 5% was employed. All molars submitted to access cavity developed AP. All joints subjected to arthritis induction developed the disease, with AP + RA demonstrating a higher arthritis severity when compared to the RA group (p < .05). RA + AP group displayed a significantly larger hind paw and knee circumference compared to the RA group (p < .05). Micro-CT images of RA and RA + AP groups revealed joints with erosions and bone deformities, with a significantly lower bone surface density, lower trabecular number and higher trabecular separation in the hind paw and a significantly lower percent bone volume and higher trabecular separation in the knees of RA + AP group compared to RA group (p < .05). RA + AP group exhibited a significantly higher level of TNF-α and a lower level of IL-2 compared to all other groups (p < .05). Both RA and RA + AP groups had significantly higher IL-17 levels (p < .05), while there was no significant difference in IL-1β levels among the groups (p > .05). The findings from this study underscore a possible relationship between apical periodontitis and the exacerbation of rheumatoid arthritis.

Increase Toll-like receptors 2 and 4 in apical periodontitis of rats with chronic liver disease.

The aim of this study was to evaluate the influence of liver fibrosis (LF) on the expression of Toll-like receptors (TLR) 2 and 4 in apical periodontitis (AP) in Wistar rats. Forty Wistar rats were allocated in the following groups (n = 10): C-control; AP-apical periodontitis; LF-liver fibrosis; AP + LF-rats with AP and LF. LF and AP were induced by established methodologies. Histological, bacteriological, and immunohistochemical analyses were performed according to pre-established scores. For comparisons between AP and AP + LF groups, the Mann-Whitney test was used (P < .05). The livers of the LF and AP + LF groups showed generalized portal inflammatory infiltrate and collagen fibers confirming the presence of LF. Histopathological analysis in the maxilla of the AP + LF group showed areas of necrosis comprising the entire dental pulp and periapical tissue surrounded by a more intense inflammatory infiltrate than observed in the AP group (P = 0.032). A significant number of specimens in the AP + LF group showed microorganisms beyond the apical foramen adhered to the extraradicular biofilm, demonstrating greater invasion compared to the AP group (P = .008). Immunohistochemical analysis showed a large number of cells immunoreactive for TLR2 and TLR4 in the AP + LF group, compared to the AP group (P < 0.05). Liver fibrosis favors the inflammation and contamination of microorganisms in apical periodontitis and triggers the expression of TLR2 and TLR4, modulating innate immunity response in periapical lesions.

The importance of mechanosensitive cell mediated prostaglandin and nitric oxide synthesis in the pathogenesis of apical periodontitis: comparative with chronic periodontitis

ObjectivesMechano-sensitive odontoblast cells, which sense mechanical loading and various stresses in the tooth structure, synthesize early signaling molecules such as prostaglandin E2 (PGE2) and nitric oxide (NO) as an adaptive response. It is thought that these synthesized molecules can be used for the diagnosis and treatment of periodontal and periapical diseases. The aim of this study was to investigate the relationship between the severity of apical periodontitis (AP) and chronic periodontitis (CP) and serum (s) TNF-α, IL-10, PGE2 and NO levels, as well as PGE2 and NO levels in gingival crevicular fluid (GCF) samples.Materials & methodsA total of 185 subjects were divided into three categories: AP group (n = 85), CP group (n = 50) and healthy control group (n = 50). The AP group was divided into 3 subgroups according to abscess scoring (AS-PAI 1, 2 and 3) based on the periapical index. The CP group was divided into 4 subgroups according to the periodontitis staging system (PSS1, 2,3 and 4). After recording the demographic and clinical characteristics of all participants, serum (s) and gingival crevicular fluid (GCF) samples were taken. TNF-α, IL-10, PGE2 and NO levels were measured in these samples.ResultsUnlike serum measurements (sTNF-α, sIL-10, sNO and sPGE2), GCF-NO and GCF-PGE levels of the AP group were significantly higher than the control group in relation to abscess formation (54.4 ± 56.3 vs. 22.5 ± 12.6 µmol/mL, p < 0.001 and 100 ± 98 vs. 41 ± 28 ng/L, p < 0.001, respectively). Confirming this, the GCF-NO and GCF-PGE levels of the AS-PAI 1 group, in which abscesses have not yet formed, were found to be lower than those in AS-PAI 2 and 3, which are characterized by abscess formation [(16.7(3.7-117.8), 32.9(11.8-212.8) and 36.9(4.3-251.6) µmol/mL, p = 0,0131; 46.0(31.4–120.0), 69.6(40.3-424.2) and 74.4(32.1–471.0) ng/L, p = 0,0020, respectively]. Consistent with the increase in PSS, the levels of sTNF [29.8 (8.2-105.5) vs. 16.7(6.3–37.9) pg/mL, p < 0.001], sIL-10 [542(106–1326) vs. 190(69–411) pg/mL, p < 0.001], sNO [182.1(36.3–437) vs. 57.0(15.9–196) µmol/mL, p < 0.001], sPGE2 [344(82-1298) vs. 100(35-1178) ng/L, p < 0.001], GCF-NO [58.9 ± 33.6 vs. 22.5 ± 12.6 ng/L, p < 0.001] and GCF-PGE2 [ 99(37–365) vs. 30(13–119), p < 0.001] in the CP group were higher than the control group. Comparison ROC analysis revealed that the GCF-PGE2 test had the best diagnostic value for both AP and CP (sensitivity: 94.1 and 88.0; specificity: 64.0 and 78.0, respectively; p < 0.001).ConclusionsGCF-PE2 and GCF-NO have high diagnostic value in the determination of AP and CP, and can be selected as targets to guide treatment. In addition, the measurements of PGE2 and NO in GCF can be used as an important predictor of pulpal necrosis leading to abscess in patients with AP.Clinical relevanceIn this article, it is reported that syntheses of early signaling molecules such as PGE2 and NO can be used for the diagnosis and treatment target of periapical and periodontal infections.

Effect of Orthodontic Treatment on the Outcomes of Endodontically Treated Teeth: A Cone-Beam Computed Tomography Analysis

IntroductionOften there is the need of moving endodontically treated teeth. Orthodontic movement may have no effect on the prognosis of teeth with root canal treatment (RCT). To verify this subject, we evaluated the effect of orthodontic movement on the prognosis of RCT teeth using cone-beam computed tomography (CBCT) and further explored the influence of orthodontic movement on the prognosis of RCT teeth with and without apical periodontitis (AP). MethodsThis retrospective study was conducted by evaluating 169 RCT teeth of 100 patients who had undergone fixed orthodontic treatment. AP was assessed and classified using the CBCT periapical index. Univariate analysis of RCT outcome was performed for the total RCT group, RCT without AP group and RCT with AP group. Multivariate logistic regression was performed for the total RCT group and RCT without AP group, respectively, but not for the RCT with AP group. Variables related to the prognosis of RCT were included, such as age, gender, tooth position, RCT quality, coronal restoration quality, periodontal condition, orthodontic traction distance, and orthodontic rotation angle. ResultsThe orthodontic traction distance and rotation angle were not significantly correlated to the RCT outcomes, regardless of the presence of AP. Among the total RCT group, teeth with unqualified RCT (odds ratio = 3.42, P = .004) and inadequate coronal restoration (odds ratio = 4.40, P = .031) had a lower success rate. Of the 97 RCT teeth without AP, unqualified RCT was a risk factor for treatment failure (odds ratio = 3.55, P = .041). Of the 72 RCT teeth with AP, the univariate analysis showed that RCT quality were significantly related to the outcome (P = .042). ConclusionsOrthodontic movement had no effect on the prognosis of RCT teeth regardless of the presence of AP.

Endodontic Treatment of Chronic Apical Periodontitis Ameliorates Systemic Inflammation and Restores Impaired Cellular Responses to Insulin in an In Vitro Model

IntroductionA growing body of research supports an association between periapical inflammation and an increased risk of developing systemic diseases. There is currently no scientific evidence to support a causal effect of inflammation on the onset of insulin resistance (IR) in patients with apical periodontitis (AP). The aim of this in vitro study was to evaluate any association between AP and levels of serum inflammatory factors potentially associated with the onset of IR, and to investigate the effect of root canal treatment (RCT) on these systemic inflammation markers and on the response in vitro to insulin. MethodsA total of 27 control subjects and 27 patients with AP were enrolled. Patients with AP underwent RCT and were followed-up 6 and 12 months post-treatment. Enzyme-linked immunosorbent assays were used to evaluate serum levels of proinflammatory cytokines interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α. The response in vitro to insulin was assessed by measuring glucose consumption in a human pancreatic epithelioid carcinoma cell line treated with sera from healthy and AP subjects. ResultsAt baseline AP was associated with significant higher levels of IL-1, IL-6, and IL-8 in the serum of untreated (AP) patients vs controls (P < .001). Glucose consumption decreased in pancreatic cells incubated with baseline serum from patients with AP, in a manner proportional to total cytokines amount. Notably, endodontic treatment was associated with reduced levels of cytokines (P < .001) and improved response to insulin in AP group (P < .001). ConclusionsOur findings suggest that AP may promote inflammatory-driven IR in an in vitro model, and that RCT may ameliorate inflammatory mediators in vivo and the cellular response to insulin in vitro.

Physical training attenuates systemic cytokine response and tissue damage triggered by apical periodontitis

Apical periodontitis (AP) is a condition characterized by inflammatory and infectious components in the tooth canal. AP affects periradicular tissues and has systemic repercussions. Physical exercise is a structured activity that requires cardiorespiratory function, and can modulate the inflammatory profile in pathological conditions. As a result, this study aimed to determine the effects of aerobic physical training (PT) on the alveolar bone with and without AP, and its systemic inflammatory repercussions. AP was induced in the mandibular first molars, and PT was performed on a treadmill for five consecutive days over four weeks, with progressive increases in speed and activity time. Blood samples were collected to determine serum cytokine levels using immunoassays, and alveolar bone samples were collected for histopathological evaluation, lesion volume and microarchitecture assessment using computed microtomography. Animals with AP had increased pro-inflammatory cytokines levels compared to those without AP; however, these levels were attenuated or restored by PT. Compared to the AP group, the AP + PT group had a smaller lesion volume and greater preservation of the bone trabeculae in the remaining alveolar bone surrounding the lesion. In overall, PT minimized the severity of AP proving to be a valid strategy for individuals undergoing endodontic treatment.

Effects of melatonin against experimentally induced apical periodontitis in rats.

Apical periodontitis is an inflammatory condition resulting from microbial invasion in the root canal system, causing periapical tissue destruction and bone resorption. This study investigated melatonin's effects, known for its antioxidant and anti-inflammatory properties, on experimentally induced apical periodontitis in rats. Three groups of rats were studied: control, apical periodontitis and apical periodontitis with melatonin treatment. Proinflammatory cytokines and enzyme levels in blood serum were measured, and micro-CT analysis assessed bone resorption. Results showed significantly elevated cytokines and enzyme levels in the apical periodontitis group compared to the control. However, in the melatonin-treated group, these levels were significantly reduced (p < 0.01-0.001). Micro-CT analysis indicated decreased periapical resorption cavity volume and surface area with melatonin treatment. This suggests that systemic melatonin administration can mitigate inflammation and reduce bone resorption in experimentally induced apical periodontitis in rats, potentially holding promise for human endodontic disease treatment pending further research.

Experimental apical periodontitis alters salivary biochemical composition and induces local redox state disturbances in the salivary glands of male rats.

The objective was to evaluate the effects of experimental apical periodontitis on the inflammatory, functional, biochemical, and redox parameters of the parotid and submandibular glands in rats. Twenty 12-week-old male Wistar rats were randomly divided into two groups (n = 10): a control group and apical periodontitis group. After 28days, the saliva was collected for salivary flow rate and biochemistry composition. Both glands were sampled for quantification of the tumor necrosis factor-alpha (TNF-α) and biochemical analyses of redox state. TNF-α concentrations were higher in both salivary glands adjacent to the periapical lesions in animals with apical periodontitis and also compared to the control group. The apical periodontitis group increased the salivary amylase, chloride, potassium, calcium, and phosphate. The total oxidant capacity increased in the parotid gland adjacent to the periapical lesions in the same rat and compared to the control group. Conversely, the total antioxidant capacity of the parotid glands on both sides in the apical periodontitis group was lower than that in the control group. Furthermore, glutathione peroxidase activity increased in the submandibular gland adjacent to the apical periodontitis group compared to the control group. Experimental apical periodontitis alters salivary biochemical composition, in addition to increasing inflammatory marker and inducing local disturbances in the redox state in the parotid and submandibular glands of male rats. Apical periodontitis could exacerbate the decline in oral health by triggering dysfunction in the salivary glands.

Relationship of MMP-9 with the clinical course of apical periodontitis and the main bacterial species in the oral microbiota.

Bacterial products, host immune cells and cytokines have been reported to play an important role in the pathogenesis of apical periodontitis (AP). This study aimed to determine the main bacterial species in the microbiota as gram positive and negative and to compare the relationship between matrix metalloproteinase (MMP)-9 and tumor necrosis factor (TNF)-α with controlled patient groups. 60 patients with AP and extraction indication were included in the study. 30 systemically healthy volunteers without AP were selected as the control group. After access cavity preparation, an initial microbiologic sample (S1) was taken from the root canal. After atraumatic extraction of the tooth, a second microbial sample (S2) was taken from the extraradicular region. After bacterial DNA extraction, 16S rRNA gene primer was designed for sequence analysis. Bacterial community profiling was made by Sanger sequencing of the PCR products. In addition, serum MMP-9 and TNF-α levels were measured from all patients. TNF-α levels of the AP group were higher than the control group, while MMP-9 levels were found to be lower (p = 0.0264 and p = 0.0146, respectively). There was no difference in the main bacterial species isolated from the samples taken from the intracanal and extraradicular region of the tooth with AP (p = 0.714). The main bacterial species in the intracanal region of the tooth with AP are similar to the main bacterial species in the extraradicular region. The pathophysiology of the tooth with AP is associated with low MMP-9 and high TNF-α, independent of the bacterial species in the intracanal and extraradicular regions.

Radiographic Criteria for Differential Diagnosis Between Vertical Root Fracture and Apical Periodontitis in Single-Rooted Endodontically Treated Premolars Using Cone-Beam Computed Tomography

IntroductionThis study explores the differences between the patterns of bone defects associated with vertical root fracture (VRF) and apical periodontitis (AP) in single-rooted endodontically treated premolars (SRETPs) based on cone-beam computed tomography (CBCT) data. MethodsEighty-four SRETPs were extracted and categorized into the VRF and AP groups. On preoperative CBCT images, the location of bone defects according to the root thirds in buccolingual and mesiodistal directions across the study groups were compared. ResultsThe majority of bone defects in the VRF group were longitudinal and combined, involving more than one root thirds in buccolingual and mesiodistal directions simultaneously. A uniform approach to comparing bone defects using the sites of periradicular area with bone loss as a comparison unit was developed. In the VRF group, bone loss sites in the middle and coronal thirds were detected more often and were located mainly buccolingually compared with the AP group (P < .001). ConclusionBone defects in the middle or middle and coronal root thirds in the buccolingual direction may be potential radiographic signs useful in differentiating between VRF and AP in SRETPs. The introduction of the uniform approach to assessment of bone loss patterns will give practitioners a single simple tool and improve the quality of endodontic treatment.

Comparative oral metagenome insight into acute and chronic root canal infections

Background: In the dynamic progression of root canal infections, the resultant change in environmental conditions directs the adaptation of the microbiome in terms of richness, evenness, and diversity. Objective: The goal of this study is to contrast the interradicular bacterial community structures of teeth in acute and chronic stages and investigate potential microorganisms associated with persistent apical periapical infections. Methods: Interradicular samples were collected from 10 teeth in the apical periodontitis group and 10 teeth in the chronic apical periodontitis group. High-throughput next-generation sequencing (NGS)–based microbial identification through the Illumina platform was used to characterize the complex intraradicular microbial communities in acute and chronic root canal infections. Results: Bacteria were the major domain, with a prevalence of &gt;97% (acute cases: 98.11% and chronic cases: 97.6%) compared to eukaryotes and archaea. Bacterial diversity was relatively higher in acute compared to chronic conditions under 10 and 9 phyla, 79 and 64 genera, and 172 and 135 species, respectively. These endodontically infecting bacteria belonged to Firmicutes (47.21%), Bacteroidetes (20.07%), and Proteobacteria (10.72%) in acute conditions, while in the chronic stage, Firmicutes (40.85%), Proteobacteria (27.80%), and Actinobacteria (14.79%) were abundant. The phylum Candidatus Saccharibacteria was exclusively found in acute samples. Spirochaetes and Synergistetes were found predominantly in acute infections compared to chronic infections. Bacillus and Lactobacillus were found in equal and highest abundance under the phylum Firmicutes in both conditions. Conclusion: This study provides information on the differential microbial community present in the apical root canal system of teeth with acute and chronic apical periodontitis and contributes to new approaches or channels for future research on preventive measures and therapeutic protocols during disease progression and treatment. However, functional characterization and detection of antimicrobial resistance in these two clinical conditions can supplement these findings for deciding routine drug treatment for periodontal infections.

Apical periodontitis and autoimmune diseases-should we be screening patients prior to therapy?

A single-centre retrospective case-control study from 2012-2020 comparing the prevalence of apical periodontitis (AP) in patients with autoimmune disorders (AD) against a control group of those without. The different medication groups commonly used for treatment of AD were included for comparison. This study utilised patients' electronic records. These were anonymous. Patient sociodemographic variables were collected and compared. Two cases were removed from selection as they were being treated with dual biologic therapy. Both the control group and AP group contained 89 patients. Various additional variables were considered, such as DMFT and a logistical regression analysis was used to correlate between AD and AP. For the autoimmune disease conditions within this study, the authors found a higher prevalence of apical periodontitis than in the control group, 89.9% versus 74.2%, respectively (p = 0.015). Furthermore, those taking conventional disease-modifying drugs such as methotrexate had a lower prevalence than those on biologics. These results were of statistical significance. Individuals with autoimmune disorders may have increased prevalence of apical periodontitis irrespective of their treatment with biologics or not. A DMFT score can be used to predict the occurrence of AP.

Is oxidative stress involved in the hepatic inflammatory response to apical periodontitis? A comparative study in normal and hyperlipidaemic rat.

The aim of the study was to explore the involvement of oxidative stress (OS) in the hepatic inflammation induced by apical periodontitis (AP). Periapical, systemic and hepatic reaction to AP under hyperlipidaemia was also investigated. A total of 16 male Sprague-Dawley rats were fed with a hyperlipidaemic diet (HD) whereas another 16 rats with a normal diet (ND). After 9 weeks, the first molars of the right maxilla and mandible of 8 HD and 8 ND rats were exposed to induce AP (ND, ND + AP, HD and HD + AP group). After 5 weeks, rats were euthanized, the haematological tissue was collected directly from the heart, and serum levels of inflammatory cytokines were measured. Liver tissue was analysed by haematoxylin-eosin and Masson staining, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect mRNA expression of inflammatory cytokines. Serum, periapical, and hepatic OS parameters including total oxidant status (TOS), total antioxidant capacity (TAOC) and oxidative stress index (OSI) were measured by enzyme-linked immunosorbent assay (ELISA). The area of AP lesion in the right maxilla or mandible was radiographically assessed. Student's t-test was performed on the periapical data. A one-way analysis of variance and the Kruskal-Wallis test were analysed for others. The HD + AP group had a larger AP lesion in the maxilla, compared with the ND + AP group (p < .05). The ND + AP group presented higher serum interleukin (IL)-18, IL-1β, TOS, OSI levels, lower serum TOAC levels, higher hepatic tumour necrosis factor (TNF)-α mRNA expression and higher hepatic TOS, and OSI levels, compared with the ND group (p < .05). The HD + AP group had lower serum IL-4 level, higher serum IL-1β level, and higher hepatic IL-6 and transforming growth factor (TGF) -β1 mRNA expression, compared with the HD group (p < .05). Apical periodontitis could activate systemic and liver inflammation by promoting serum IL-18, 1L-1β, TOS and OSI expression, enhancing hepatic TOS and OSI expression and inhibiting serum TOAC expression. AP under hyperlipidaemia led to more profound periapical bone destruction in the maxilla and elicit systemic and liver inflammatory responses through elevating serum levels of IL-1β, descending serum IL-4 level and improving hepatic IL-6 and TGF-β1 expression.

Inflammatory profile of apical periodontitis exacerbated by cigarette smoke inhalation: Histological and immunohistochemical analysis in rats.

The aim of this study was to evaluate the effects of cigarette smoke inhalation (CSI) on inflammation, pro-inflammatory mediators and haematological parameters in rats with induced apical periodontitis (AP). Thirty-two 3-month-old male Wistar rats were divided into four experimental groups (n=8): C-Control; S-rats with CSI; AP-rats with AP; and SAP-rats with CSI + AP. Animals in groups S and SAP inhaled cigarette smoke by remaining inside a smoking chamber for 8 min, three times daily, for 50 days. After 20 days of smoke inhalation, animals in AP and SAP groups had the pulps of the lower right first molar exposed to oral environment for 30 days to induce AP. In these subsequent 30 days, animals in group S and SAP continued with CSI. On Day 50, animals were euthanized and mandibles were histologically processed to assess inflammatory infiltrate, immunohistochemical interleukins (IL-1β, IL-6 and TNF-α), and blood samples collected for laboratory analysis. The Mann-Whitney test was performed for non-parametric data and the pairwise analyses of Student's t-test for parametric data, with a significance level of p < .050. Inflammatory infiltrate was moderate in AP group and more severe in the SAP (p=.010). The interleukins IL-6, IL-1β and TNF-α were higher in SAP group (p < .001) when compared to the AP group. A greater number of red blood cells (p=.010), haemoglobin (p=.007) and neutrophils (p=.014) were observed in the SAP group in comparison with the AP group. Cigarette smoke inhalation induced a more severe inflammatory infiltrate, with increased levels of pro-inflammatory cytokines and changes in haematological parameters in rats with induced AP. Thus, CSI aggravated AP, exacerbating the inflammatory response.

Effects of adjacent periodontitis on osseointegrated dental implants.

This study aimed to investigate whether new-onset periodontitis or apical periodontitis in the adjacent teeth affects osseointegrated dental implants in a beagle dog model. One control group and 2 experimental groups (periodontitis and apical periodontitis groups) were defined based on the presence of experimental periodontitis or apical periodontitis, with 1 beagle dog randomly assigned to each group. The mandibular second and fourth premolars on both sides of the 3 beagles were extracted. Eight weeks after extraction, 4 bone-level implant fixtures, 2 on both sides of each mandible, were placed in each beagle. Six weeks after implant surgery, healing abutments were connected. After sufficient osseointegration, plaque control was performed in the control group, while periodontitis and apical periodontitis were induced in the experimental groups. The beagles were euthanized for histological analyses 20 weeks after induction of experimental periodontitis. Statistical analyses were performed using the Kruskal-Wallis test with the Bonferroni correction to compare the 3 groups. The implants in the control and apical periodontitis groups were well-maintained, while those in the periodontitis group showed clinical signs of inflammation with bone resorption. The bone-to-implant contact (BIC) and bone area values in the periodontitis group were lower than those in the other groups. The distance between the implant shoulder and the first BIC was significantly greater in the periodontitis group than in the control group (P<0.05). The presence of periodontitis in adjacent teeth can pose a risk to dental implants, potentially resulting in peri-implantitis. However, this was not observed for apical periodontitis. Within the limitations of this study, periodontal care is necessary to reduce the impact of periodontitis in adjacent teeth on osseointegrated implants.

Melatonin decreases IRF-3 protein expression in the gastrocnemius muscle, reduces IL-1β and LPS plasma concentrations, and improves the lipid profile in rats with apical periodontitis fed on a high-fat diet.

To evaluate the effects of melatonin (MEL) on the expression of toll-like receptor-4 (TLR4); myeloid differentiation primary response protein-88 (MyD88); TIR-domain-containing adapter-inducing interferon-β (TRIF); IFN regulatory-factor-3 (IRF-3); nuclear factor kappa-B (NF-κB); plasma concentrations of interleukin-1β (IL-1β) and lipopolysaccharide (LPS); and lipid profile of rats with apical periodontitis (AP) fed on a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control, AP, HFD, HFDAP, CNMEL, APMEL, HFDMEL and HFDAPMEL. HFD groups were fed on a HFD for 107days. On day 7, experimental AP was induced in the AP groups, and after 70days, MEL (5mg/kg) was administered to the MEL groups for 30days. Plasma concentrations of LPS and IL-1β were analyzed using enzyme-linked immunosorbent assay, and the lipid profile was analyzed using biochemical tests. The expression of proteins involved in the TLR4 pathway (TLR4, MyD88, TRIF, IRF-3 and NF-κB) in the gastrocnemius muscle (GM) was evaluated using western blotting and qRT-PCR. Treatment with MEL decreased IRF-3 protein expression in GM and IL-1β plasma concentration in the APMEL and HFDMEL groups. Reduction in LPS plasma concentration was reported only in the HFDMEL group. Additionally, a decrease in LDL and an increase in HDL were observed in the HFDMEL and HFDAPMEL groups. Treatment with MEL exhibited anti-inflammatory and anti-hyperlipidemic effects attributed to HFD and AP by reducing the plasma concentrations of IL-1β and LPS in addition to reducing IRF-3 protein expression in the GM, which is associated with the production of inflammatory cytokines.

Early life stress exacerbates bone resorption and inhibitsanxiety-like behaviour induced by apical periodontitis in rats.

To evaluate the influence of the early life stress (ELS) on the severity of the apical periodontitis (AP) in Wistar rats. Forty male Wistar rats were divided into four groups (n=10): Control rats; AP-rats with AP; ELS-rats subject to ELS; AP + ELS-rats exposed to ELS and subject to AP. ELS was induced by maternal separation (MS) for a period of 3h for 21 consecutive days. AP was induced via pulp exposure of the first and second right maxillary molars to the oral environment for 40 days. Three days before euthanasia, all rats underwent behavioural analysis to measure anxiety levels by elevated zero maze. Then, the rats were euthanized and the maxillas were removed to assess the occurrence and severity of AP. The periapical region was evaluated for the intensity of the inflammatory infiltrate and the extent of bone loss. The Mann-Whitney test was performed for nonparametric data, and the Tukey's or Student's t-test was performed for parametric data (p < .05). The intensity of the inflammatory infiltrate was significantly larger in the AP + ELS group when compared with AP group (p < .05). The AP + ELS group exhibited significantly greater alveolar bone loss, with a periapical lesion size of 103.5 ± 29.88, compared with 72.3 ± 22.28 in the AP group (p < .05). Rats with AP displayed higher anxiety-like behaviour in relation to the control group (p < .05). However, exposure to ELS abolished the AP-induced increased anxiety-like 'behaviour' throughout, since that rats from AP + ELS group attended more the open arms than non-stressed rats with AP (p < .05). Early life stress is predictive of the severity of AP exacerbating the inflammatory process and increasing periapical bone resorption.

The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: A prospective case-control study.

To explore the influence of apical periodontitis (AP) on inflammatory markers in blood of otherwise healthy individuals and to depict the inflammatory profile of the healing after dental extraction. This is a prospective case-control intervention study, during which, individuals with a diagnosis of AP of one affected tooth were included, along with a control group matched for age and gender. A broad panel of blood inflammatory mediators was examined longitudinally in all subjects during six visits. In the case of the AP subjects, the tooth with AP was extracted at the third visit. Results were analysed by linear regression analyses and linear mixed-model analyses. A total of 53 subjects were included in the study, 27 with AP and 26 without. Fifteen females and 12 males were included in the AP group, and 14 females and 12 males in the control group. At baseline, granulocyte colony-stimulating factor(p < .001), interleukin (IL)-1β (p=.03) and IL-4 (p=.01) were significantly lower in AP subjects than in controls. Comparison of the differences between baseline and the last visit, i.e. 3 months after the tooth extraction, showed a significant reduction in IL-10 (p=.03) and IL-12p70 (p=.01). The immunologic profile of chronic AP in one tooth and its healing profile reveals a systemic low-grade inflammation through compensatory immunosuppression. A larger lesion or multiple lesions could disrupt the balance that the system is trying to maintain, resulting in loss of homeostasis.

Melatonin decreases plasma TNF-α and improves nonenzymatic antioxidant defence and insulin sensitivity in rats with apical periodontitis fed a high-fat diet.

To analyse the effects of melatonin (ME) treatment on oxidative stress and insulin resistance (IR) in rats with apical periodontitis (AP) fed a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control (CN), AP, HFD with AP (HFDAP), control with ME (CNME), AP with ME (APME), HFD with ME (HFDME) and HFD with AP+ME (HFDAPME). The animals from the HFD groups were fed a HFD throughout the experimental period. On day 7, the animals from the AP groups were subjected to experimental AP, and after 70 days, the ME groups were treated for 30 days. Glycaemia, insulinaemia, homeostatic model assessment for IR index, tumour necrosis factor-α (TNF-α), and interleukin-6 were analysed in plasma using biochemical tests and enzyme-linked immunosorbent assay. Thiobarbituric acid-reactive substances (TBARS), carbonyl protein (CP), superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione (GSH) and total antioxidant capacity (ferric reducing antioxidant power [FRAP]) were analysed in the gastrocnemius muscle. (1) Association of AP and HDF exacerbated IR, and ME treatment improved this alteration; (2) AP and HFD and their association showed increased TNF-α, and ME reversed it; (3) TBARS increased in the AP and HFDAP groups, and ME reversed only in the group with the association of disease and diet; (4) CP increased in all HFD groups and improved in the ME groups; (5) GSH activity decreased in all experimental groups, and ME increased this parameter only in the CN and AP groups; (6) FRAP did not change between the groups, but ME treatment increased its activity in the AP and HFD groups; (7) ME increased SOD in the CN and AP groups. Apical periodontitis and HFD promoted IR, and the association of AP with diet promoted IR exacerbation; this resistance might have been caused by an increase in TNF-α. AP promoted more intense changes in lipid oxidative damage than in protein oxidative damage. In non-enzymatic antioxidant defence, it was observed that both AP and HFD and their association promoted a decrease in GSH levels. Overall, ME treatment reversed changes such as oxidative stress and IR.

Effect of maternal true combined endodontic-periodontal lesion on insulin and inflammatory pathway in adult offspring.

Maternal periodontal disease (PED) and apical periodontitis (AP) are associated insulin resistance (IR), increased tumor necrosis factor-α (TNF-α) levels, and alterations in insulin signaling (IS) in the gastrocnemius muscle (GM) of adult offspring. TNF-α stimulates I kappa B kinase (IKK) and c-Jun N-terminal protein kinase (JNK), resulting in IS attenuation. However, studies that investigated the maternal true endodontic-periodontal lesion (EPL) in offspring are scarce, and in this case, the impact could be even higher. This study aimed to evaluate the effects of EPL on the IR, IS, and inflammatory pathways on the offspring GM. Female Wistar rats were distributed into control, AP, PED, and EPL groups. After 30 days of oral inflammation induction, rats from all groups were allowed to mate with healthy rats. The body weight of the offspring was assessed from birth to 75days of age. After 75days, the following measurements were performed: glycemia, insulinemia, IR, TNF-α content, and IKKα/β, JNK, pp185 (Tyr), and IRS-1 (Ser) phosphorylation status in the GM. Maternal PED and EPL were associated with low birth weights. All maternal oral inflammations promoted IR and IS impairment in the GM and only maternal PED and EPL caused an increase in TNF-α content and IKKα/β phosphorylation status in the GM of offspring. The offspring of the rats with EPL group showed worsening of metabolic changes when compared with offspring of rats with AP or PED. Association of maternal AP and PED promoted a more pronounced worsening in the health of the adult offspring.