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Aim: To evaluate the effect of red wine consumption or its polyphenols on the inflammation/resorption processes associated with apical periodontitis in rats., Methodology: Thirty-two three-month-old Wistar rats had apical periodontitis induced in four first molars and were then arranged into four groups: control (C)-rats with apical periodontitis; wine (W)-rats with apical periodontitis receiving 4.28 ml/kg of red wine; resveratrol+quercetin (R+Q)-rats with apical periodontitis receiving 4.28 ml/kg of a solution containing 1.00 mg/L of quercetin and 0.86 mg/L of resveratrol and alcohol (ALC)-rats with apical periodontitis receiving the alcoholic dose contained in the wine. The oral gavage treatments were administered daily, from day 0 to day 45. On the 15th day, apical periodontitis was induced, and on the 45th day, the animals were euthanized. Histological, immunohistochemical (RANKL, OPG, TRAP, IL-10, TNF-⍺ and IL-1β) and micro-computed tomography for bone resorption analysis were performed in the jaws. The Kruskal-Wallis with Dunn's test was performed for nonparametric data, and the anova with Tukey's test for parametric data, p < .05., Results: The median score of the inflammatory process was significantly lower in the R+Q group (1) compared to the C (2) (p = .0305) and ALC (3) (p = .0003) groups, and not different from the W (1.5) group. The immunolabeling for OPG was significantly higher in the R+Q group (p = .0054) compared to all groups; the same was observed for IL-10 (p = .0185), different from groups C and ALC. The R+Q group had the lowest TRAP cell count (p < .0001), followed by the W group, both inferior to C and ALC groups. The lowest bone resorption value was in the R+Q group (0.50mm 3  ± 0.21mm 3 ), significantly lower (p = .0292) than the C group (0.88mm 3  ± 0.10mm 3 ). The W group (0.60 mm 3  ± 0.25 mm 3 ) and R+Q group had less bone resorption compared to the ALC group (0.97 mm 3  ± 0.22 mm 3 ), p = .0297 and p = .0042, respectively., Conclusion: Red wine administration to rats for 15 days before induction of apical periodontitis decreased inflammation, TRAP marking and periapical bone resorption compared to alcohol. Resveratrol-quercetin administration reduced the inflammatory process in apical periodontitis, periapical bone resorption, and altered the OPG, IL-10 and TRAP expression compared to C and ALC groups., (© 2021 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Aim: To evaluate the effect of excessive caffeine intake on the inflammation/resorption processes associated with periapical periodontitis (PP) in rats., Methodology: Sixteen Wistar rats were used. Periapical periodontitis was induced in the four first molars in each animal. The animals were arranged into two groups: control (C)-rats with periapical periodontitis; and caffeine (CAF)-rats with periapical periodontitis under caffeine administration protocol. The CAF animals received 10 mg/100 g of body weight/day of caffeine via gavage starting fifteen days before PP induction and continuing for thirty more days until euthanasia. On the 30th day, the animals were euthanized and the jaws removed for microcomputed tomography, histological and immunohistochemical analysis for RANKL, OPG, TRAP, IL-10, TNF-⍺ and IL-1β. The Mann-Whitney test was performed for nonparametric data, and Student's t test was performed for parametric data, using p < .05., Results: There was no significant difference in the weight change between the groups. The median score of the inflammatory process was significantly greater in the CAF group (3) compared with the C group (2), p = .0256. Bone resorption was greater in the group consuming caffeine (1.08 ± 0.15 mm 3 ) compared with the C group (0.88 ± 0.10 mm 3 ), p = .0346. The immunolabelling for RANKL, TRAP and IL-1β was significantly higher in the CAF group when compared to the control, p < .05. No differences were found for the OPG, IL-10 and TNF-⍺ immunolabelling., Conclusion: Excessive caffeine exposure via gavage in rats was able to exacerbate the volume of periapical bone destruction, and the inflammatory pattern deriving from periapical periodontitis altering the expression of RANKL, IL-1β and TRAP., (© 2021 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Endodontics has gained emphasis in the scientific community in recent years due to the increase in clinical and in animal models studies focused on endodontic medicine, which aims to evaluate the interrelationship between systemic and periapical tissues pathological conditions. These studies have shown that systemic changes can boost the pathogenesis of endodontic infection, favoring its development and progression. A contrary relationship is reported in numerous studies that affirm the potential of endodontic infection to trigger systemic damage and may lead to the worsening of pre-existing pathologies. Recently, the potential of filling materials to develop systemic changes such as neurological alterations had been evaluated, also showing that systemic diseases can negatively influence tissue responses to filling materials after endodontic treatment. Despite advances in endodontic medicine studies, there are still gaps in knowledge on the mechanisms of interactions between apical periodontitis (AP) and systemic diseases and much research to be done. In this sense, this critical narrative literature review aimed to show the evolution of studies in endodontic medicine to help the endodontist to know the role of systemic diseases in the pathogenesis of AP and the possible interference in the repair of periapical tissues after endodontic treatment, as well as to evidence the systemic complications that can be triggered or aggravated in the presence of endodontic infection., (© 2021. The Society of The Nippon Dental University.)

Objective: The aim of this study was to evaluate whether probiotics multi-strain formula affects the development of apical periodontitis (AP) induced in rats., Methodology: 16 Wistar rats were divided in two groups (n=8): rats with AP fed with regular diet (Control-C (CG)); rats with AP, fed with regular diet and supplemented with multi-strain formula (one billion colony-forming units (CFU)): GNC Probiotic Complex (PCG) ( Lactobacillus acidophilus, Lactobacillus salivaris, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium animalis subs. lactis and Streptococcus thermofilus ). AP was induced in the upper and lower first molars by dental pulp exposure to the oral environment. PCG was administered orally through gavage for 30 days during the AP development. After this period the animals were euthanized and the mandibles were removed and processed for histologic analysis, and immunochemical assays for interleukin (IL)-6, IL-10, IL-1β, RANKL, OPG, and TRAP. The Mann-Whitney U test and Student's t test were performed (P<.05)., Results: The CG showed more intense inflammatory infiltrate than the PCG group (P<.05). IL-1β, IL 6 and RANKL decreased in the PCG group compared with CG (P<.05). The IL-10 level increased in the PCG group (P<.05). The OPG level was similar in both groups (P>.05). The number of mature osteoclasts (TRAP-positive multinucleated cells) was lower in PCG group when compared to the CG (P<.05)., Conclusion: Probiotic Complex modulates inflammation and bone resorption in apical periodontitis.

Aim: To evaluate the relationship between systemic administration of probiotics and inflammation/resorption processes associated with apical periodontitis (AP) in a rat model., Methodology: Twenty-four male Wistar rats were used. AP was induced in the mandibular left/right first molars. The animals were arranged into three groups: Control, Lactobacillus rhamnosus and L. acidophilus. Probiotics were orally administered via gavage (10 9 colony-forming units (CFU) diluted in 5 mL of water) for 30 days during the development of AP. On the 30th day, blood was collected to analyse the calcium, phosphorus and alkaline phosphatase concentrations in plasma. Then, the animals were euthanized and the jaws removed for micro-computed tomography and immune-histopathological analysis for receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG) and tartrate-resistant acid phosphatase (TRAP). After the Shapiro-Wilk test of normality, the Kruskal-Wallis followed by Dunn's test was performed for nonparametric data, and analysis of variance followed by the Tukey test was performed for parametric data (P < 0.05)., Results: There was no significant difference in the calcium and phosphorus levels in plasma amongst the groups (P > 0.05). The level of alkaline phosphatase was significantly higher in the groups that consumed probiotics (P < 0.05). A significantly lower volume of bone resorption was observed in groups that consumed probiotics (P < 0.05). The inflammatory infiltrates and the immunolabelling for RANKL and TRAP were significantly lower in probiotic groups when compared to the control (P < 0.05). Also, the OPG was significantly more immunolabelled in the L. acidophilus group than in the L. rhamnosus and control groups (P < 0.05)., Conclusion: Probiotic supplementation through gavage (L. rhamnosus and L. acidophilus) had a significant effect on the reduction of inflammation and bone resorption in apical periodontitis development in rats., (© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Aim: To investigate the effect of different alcohol concentrations on the development of apical periodontitis (AP) in rats., Methods: Forty Wistar rats were arranged into five groups: (C) - control rats receiving sterile water as the only liquid; (G5) - animals receiving an alcohol solution at 5%, (G10) - alcohol solution at 10%, (G15) - alcohol solution at 15%, and (G20) - alcohol solution at 20%. The alcoholic solution or water was given to the groups as the sole source of hydration throughout the 30 days of the experiment. AP was induced in the mandibular molars on the first day. In the end, the animals were euthanized for histopathological and IL-1b, RANKL, OPG, and TRAP analyses. The Kruskal-Wallis test was used for nonparametric data, and ANOVA followed by the Tukey test were performed for parametric data, p < 0.05., Results: G15 and G20 had a greater chronic inflammatory infiltrate (Score 3) and AP size bigger (1.59 ± 0.41 and 1.83 ± 0.38, respectively) than the C, G5 and G10 (p < 0.05). No significant difference was found in the IL-1b analyses. The G15 and G20 showed the highest immunolabeling pattern for RANKL and the lowest for OPG. The G20 had greater TRAP cells per mm (4.70 ± 0.99) compared to the C, G5, and G10 (p < 0.05). Furthermore, G15 presented 3.92 ± 0.64 TRAP cells/mm, higher than C (p < 0.05)., Conclusions: G5 and G10 did not exert a protective or aggravating effect on the AP development. However, G15 and G20 had a significant effect on the AP severity, exacerbating the inflammation and osteoclast markers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the effect of systemic administration of probiotics on the severity of apical periodontitis (AP)., Methodology: Twenty-four male Wistar rats were used. AP was induced in the maxillary left/right first molars. The animals were arranged into groups: Control, Lactobacillus rhamnosus, and Lactobacillus acidophilus. Probiotics were administered orally for gavage (10 9 colony-forming units diluted in 5 mL of water for 30 days) during the development of AP. After 30 days, cardiac puncture was performed to analyse the complete blood count. Moreover, microbiological analysis of the root canal contents and saliva was performed. Then, the animals were euthanized and the jaw removed for histopathological and IL-10, IL-1β and IL-6 immunolabeling analyses. After the Shapiro-Wilk test of normality, the Kruskal-Wallis followed by Dunn's test was performed for nonparametric data, and analysis of variance followed by the Tukey test was performed for parametric data (P < 0.05)., Results: No significance difference was observed in the blood profiles and in the counts of microorganisms from the saliva samples among the groups (P > 0.05). Total microorganism counts in the root canal, the inflammatory infiltrate and the immunostaining for IL-1β and IL-6 in AP were significantly lower in the probiotic groups when compared with the control group (P < 0.05). IL-10 was significantly more immunolabled in the probiotic groups than in the control group (P < 0.05)., Conclusion: Supplementation with probiotics (Lactobacillus rhamnosus and Lactobacillus acidophilus) had a significant effect on the severity of apical periodontitis in rats, demonstrating the anti-inflammatory effect of probiotics on the development of apical periodontitis., (© 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Aim: The aim of the present study was to evaluate apical periodontitis (AP) development in rats under a chronic alcohol diet by calcium, phosphorus, and alkaline phosphatase blood levels in addition to histological and radiographic analyses., Methods: Thirty-two rats were arranged into four groups: (a) group 1: without apical periodontitis and on a regular diet; (b) group 2: AP and on a regular diet; (c) group 3: alcoholic diet without apical periodontitis; and (d) group 4: alcoholic diet and apical periodontitis. Alcoholic solution at 20% was given throughout the 8-week experiment. AP was induced in the first molars at the end of the 7th week. At the end, the animals were anesthetized for blood collection, followed by euthanasia, and jaws were removed for digital radiography and histological processing. The level of significance was 5%., Results: Calcium levels remained constant in all groups (P > 0.05). Group 4 showed a higher phosphorous level than group 2 (P < 0.05). The alkaline phosphatase activity was higher in group 3 compared with group 1 (P < 0.05). Three animals in group 4 exhibited a severe inflammatory reaction, whereas the animals in group 2 did not demonstrate any reaction (P < 0.05). The lowest value of radiographic density was given by group 4 (P < 0.05)., Conclusions: Chronic alcohol consumption increased serum phosphorus and decreased bone density in the periapical region, favoring AP development., (© 2019 John Wiley & Sons Australia, Ltd.)

Aim: To investigate the effect of chronic alcohol consumption on apical periodontitis in rats., Methodology: Thirty-two male Wistar rats were arranged into four groups: Control (C): without apical periodontitis and nonalcoholic diet; (AL): without apical periodontitis and alcoholic diet; (AP): with apical periodontitis and nonalcoholic diet; and (AP + AL): with apical periodontitis and alcoholic diet. The alcoholic solution at 20% was given to the AL and AP + AL groups as the sole source of hydration throughout the experiment. AP was induced in the mandibular left first molars at the end of the 4th week. Weight changes and the amount of solid and liquid foods were recorded for 8 weeks. At the end, the animals were euthanized and the jaws removed followed by histological processing for histopathological and RANKL, OPG, TRAP and HIF-1α analyses. The Mann-Whitney test was used for nonparametric data, and anova followed by the Tukey test was performed for parametric data, with P < 0.05., Results: Animals that received the alcoholic diet had a lower weight gain than the other groups (P < 0.05). Control and AL groups did not have an inflammatory response in the periapical tissues. The median score of inflammatory infiltrate was significantly higher in the AP + AL group (2.5) compared to the AP group (1.5; P < 0.05). In the same comparison, AP + AL was associated with score 3 for RANKL and HIF-1α versus score 2 for AP group (P < 0.05). Moreover, the values for TRAP were 3.88 ± 0.70 cells mm -1 for the AP + AL group and 2.43 ± 0.94 cells mm -1 for the AP group (P < 0.05)., Conclusion: In rats, an alcoholic diet had a significant effect on the severity of apical periodontitis, exacerbating the inflammatory response and osteoclastogenesis., (© 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.)