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Macedo Signorelli NS, Rende SGS, Iorio EL, Ferraz DC, Paranhos LR, Moura CCG. Identification of oxidative stress biomarkers in apical periodontitis: A scoping review with bibliometric analysis. AUST ENDOD J 2024; 50:742-760. [PMID: 39297674 DOI: 10.1111/aej.12888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 07/08/2024] [Accepted: 08/31/2024] [Indexed: 12/13/2024]
Abstract
Oxidative stress (OS) is a ubiquitous process for protecting against microorganisms' challenges. This review maps the most used methods for obtaining samples and analysing reactive oxygen species levels in apical periodontitis, following the PRISMA Extension for Scoping Reviews and is registered in Open Science Framework ([https://doi.org/10.17605/OSF.IO/D5U76]). A systematic search was conducted in electronic databases MEDLINE (PubMed), Embase, Scopus, Web of Science, LILACS, SciElo, OATD and DANS up to 17 July 2023. A total of 18 studies were included, with periapical tissue being the most common sample. Twenty-eight different oxidative stress markers were identified, with inducible nitric oxide synthase being the most prevalent. The use of diverse biomarkers for oxidative stress assessment lacks specificity in identifying particular OS species for evaluating apical periodontitis and potential systemic effects. Studies are necessary to compare results obtained from less invasive methods (such as saliva and crevicular fluid) with those from periapical lesion samples.
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Affiliation(s)
| | | | - Eugenio Luigi Iorio
- Program in Integrative Medicine, School of Medicine, Uberaba University (UNIUBE), Uberlândia, Minas Gerais, Brazil
- International Observatory of Oxidative Stress, Salerno, Italy
- Department of Endodontics and Dental Materials, School of Dentistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | | | - Luiz Renato Paranhos
- Department of Preventive and Social Dentistry, School of Dentistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Camilla Christian Gomes Moura
- Department of Endodontics and Dental Materials, School of Dentistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
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Ferraz DC, Moura CCG, Signorelli NSM, Rosa RC, Pereira SADL, Borges ALS, Bittar VP, Duarte RMF, Teixeira RR, Bertolini M, Espindola FS. The Interaction of Apical Periodontitis, Cigarette Smoke, and Alcohol Consumption on Liver Antioxidant Status in Rats. Int J Mol Sci 2024; 25:12011. [PMID: 39596079 PMCID: PMC11593682 DOI: 10.3390/ijms252212011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 11/04/2024] [Accepted: 11/05/2024] [Indexed: 11/28/2024] Open
Abstract
This study aimed to investigate the impact of alcohol (A), secondhand cigarette smoking (ShS), and their combined effect on liver antioxidant activity and hepatic damage in rats with induced apical periodontitis (AP). Thirty-five female Wistar rats were randomly allocated into five groups (n = 7): (1) control (rats without ShS, alcoholic diet, or AP), (2) control-AP (induced AP only), (3) ShS-AP (ShS exposure and induced AP), (4) A-AP (alcoholic diet and induced AP), and (5) A+ShS-AP (alcoholic diet, ShS exposure, and induced AP). Alcohol was administered through semi-voluntary intake, while ShS exposure involved the daily inhalation of cigarette smoke. The experimental period lasted 8 weeks, with AP induction occurring in the 4th week following molar pulp exposure. Liver samples were collected post-euthanasia for histomorphometric and antioxidant marker analyses. All AP-induced groups exhibited increased liver sinusoidal dilation compared to the control group (p < 0.05). AP significantly reduced total antioxidant capacity (FRAP) across all groups (p < 0.05). In AP-induced groups, FRAP levels were further decreased in ShS-AP and A+ShS-AP compared to control-AP (p < 0.05). AP also led to a decrease in the glutathione defense system (p < 0.05). Rats with alcohol exposure (A-AP and A+ShS-AP) showed reduced glutathione peroxidase activity (p < 0.05). Glutathione reductase activity was comparable in the control and control-AP groups (p > 0.05), but significantly decreased in the alcohol and ShS-exposed groups (p < 0.05). Apical periodontitis can relate to morphological changes in the liver's sinusoidal spaces and impairment of liver's antioxidant capacity of rats, particularly when combined with chronic alcohol consumption and exposure to cigarette smoke.
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Affiliation(s)
- Danilo Cassiano Ferraz
- Department of Endodontics, School of Dentistry, Federal University of Uberlândia, Uberlândia 38405-266, MG, Brazil; (D.C.F.)
| | - Camilla Christian Gomes Moura
- Department of Endodontics, School of Dentistry, Federal University of Uberlândia, Uberlândia 38405-266, MG, Brazil; (D.C.F.)
| | - Nara Sarmento Macêdo Signorelli
- Department of Endodontics, School of Dentistry, Federal University of Uberlândia, Uberlândia 38405-266, MG, Brazil; (D.C.F.)
| | - Rodrigo César Rosa
- Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro, Uberaba 38025-180, MG, Brazil
| | | | - Ana Luiza Silva Borges
- Institute of Biotechnology, Federal University of Uberlândia, Uberlândia 38405-319, MG, Brazil (F.S.E.)
| | - Vinícius Prado Bittar
- Institute of Biotechnology, Federal University of Uberlândia, Uberlândia 38405-319, MG, Brazil (F.S.E.)
| | | | - Renata Roland Teixeira
- Institute of Biotechnology, Federal University of Uberlândia, Uberlândia 38405-319, MG, Brazil (F.S.E.)
| | - Martinna Bertolini
- Department of Periodontics and Preventive Dentistry, University of Pittsburgh, Pittsburgh, PA 15261, USA
| | - Foued Salmen Espindola
- Institute of Biotechnology, Federal University of Uberlândia, Uberlândia 38405-319, MG, Brazil (F.S.E.)
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Wen YH, Lin YX, Zhou L, Lin C, Zhang L. The immune landscape in apical periodontitis: From mechanism to therapy. Int Endod J 2024; 57:1526-1545. [PMID: 39087849 DOI: 10.1111/iej.14125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 07/04/2024] [Accepted: 07/12/2024] [Indexed: 08/02/2024]
Abstract
Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.
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Affiliation(s)
- Yuan-Hao Wen
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Yu-Xiu Lin
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Cariology and Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Lu Zhou
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Cariology and Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Chen Lin
- Department of Endodontics, Stomatological Hospital of Xiamen Medical College, Xiamen, China
| | - Lu Zhang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Cariology and Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
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Peng Z, Zhang W, Hong H, Liu L. Effect of luteolin on oxidative stress and inflammation in the human osteoblast cell line hFOB1.19 in an inflammatory microenvironment. BMC Pharmacol Toxicol 2024; 25:40. [PMID: 38997762 PMCID: PMC11241847 DOI: 10.1186/s40360-024-00764-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 07/05/2024] [Indexed: 07/14/2024] Open
Abstract
BACKGROUND Periapical lesions are characterized by periapical inflammation and damage to periapical tissues and eventually lead to bone resorption and even tooth loss. H2O2 is widely used in root canal therapy for patients with periapical inflammation. Luteolin possesses high anti-inflammatory, antioxidant, and anticancer potential. However, the underlying mechanism of the efficacy of H2O2 and luteolin on oxidative stress and inflammatory tissue has not been previously addressed. We aimed to investigate the anti-inflammatory and antioxidative effects of luteolin on H2O2-induced cellular oxidative inflammation. METHODS After human osteoblasts (hFOB1.19) were treated with lipopolysaccharide (LPS), luteolin, or H2O2, cell proliferation was analysed by using a cell counting kit-8 (CCK-8), cell apoptosis was measured by using flow cytometry, the production of reactive oxygen species (ROS) was evaluated by using an oxidation-sensitive probe DCFH-DA ROS assay kit, and the expression of genes and proteins was detected by using reverse transcription quantitative polymerase chain reaction (RT‒qPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). RESULTS We demonstrated that inflammation is closely related to oxidative stress and that the oxidative stress level in the inflammatory environment is increased. Luteolin inhibited the H2O2-induced increase in the expression of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor α (TNF-α) and significantly repressed the H2O2-induced increase in ROS, as well as markedly strengthened superoxide dismutase (SOD) activity in hFOB1.19 cells. Moreover, we detected that luteolin may inhibit H2O2-induced hFOB1.19 cell injury by suppressing the NF-κB pathway. CONCLUSION We elucidated that luteolin protected human osteoblasts (hFOB1.19) from H2O2-induced cell injury and inhibited the production of proinflammatory cytokines by suppressing the NF-κB signalling pathway. Our findings provide a potential drug for treating H2O2-induced periodontitis and cell injury.
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Affiliation(s)
- Zhengjun Peng
- Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Affiliated Stomatological Hospital, Sun Yat-Sen University, 56 Lingyuan Xi Rd, Guangzhou, 510055, Guangdong, China
| | - Wenyu Zhang
- Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Affiliated Stomatological Hospital, Sun Yat-Sen University, 56 Lingyuan Xi Rd, Guangzhou, 510055, Guangdong, China
| | - Hong Hong
- Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Affiliated Stomatological Hospital, Sun Yat-Sen University, 56 Lingyuan Xi Rd, Guangzhou, 510055, Guangdong, China
| | - Lu Liu
- Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Affiliated Stomatological Hospital, Sun Yat-Sen University, 56 Lingyuan Xi Rd, Guangzhou, 510055, Guangdong, China.
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Matos-Sousa JM, Chemelo VS, Frazão DR, Bittencourt LO, de Moura JDM, Mesquita CM, Marañón-Vásquez G, Fagundes NCF, Paranhos LR, Maia LC, Monteiro MC, Lima RR. Is there any association between the presence of biomarkers and apical periodontitis? A systematic review. Front Immunol 2024; 15:1366954. [PMID: 38840914 PMCID: PMC11150667 DOI: 10.3389/fimmu.2024.1366954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 04/15/2024] [Indexed: 06/07/2024] Open
Abstract
This systematic review aimed to verify whether there is evidence of an association between apical periodontitis and the presence of systemic biomarkers. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA. For this, the acronym PECO was used; population (P) of adult humans exposed (E) to the presence of apical periodontitis, compared (C) to adult humans without apical periodontitis, and the outcome (O) of the presence of biomarkers was observed. The articles were searched in PubMed, Scopus, Web of Science, LILACS, Cochrane Library, OpenGray, and Google Scholar grey databases. Subsequently, studies were excluded based on title, abstract, and full article reading, following the eligibility criteria. The methodological quality of the selected studies was evaluated using the Newcastle-Ottawa qualifier. After exclusion, 656 studies were identified, resulting in 17 final articles that were divided into case-control, cross-sectional, and cohort studies. Eight studies were considered to have a low risk of bias, one had a medium risk of bias, and eight had a high risk of bias. In addition, 12 articles evaluated biomarkers in blood plasma, four evaluated them in saliva, and only one evaluated them in gingival crevicular fluid. The results of these studies indicated an association between apical periodontitis and the systemic presence of biomarkers. These markers are mainly related to inflammation, such as interleukins IL-1, IL-2, and IL-6, oxidative markers, such as nitric oxide and superoxide anions, and immunoglobulins IgG and IgM. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier (CRD42023493959).
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Affiliation(s)
- José Mário Matos-Sousa
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém-Pará, Brazil
| | - Victória Santos Chemelo
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém-Pará, Brazil
| | - Deborah Ribeiro Frazão
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém-Pará, Brazil
| | - Leonardo Oliveira Bittencourt
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém-Pará, Brazil
| | - João Daniel Mendonça de Moura
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém-Pará, Brazil
| | - Caio Melo Mesquita
- Department of Preventive and Social Dentistry, Faculty of Dentistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Guido Marañón-Vásquez
- Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Luiz Renato Paranhos
- Department of Preventive and Social Dentistry, Faculty of Dentistry, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Lucianne Cople Maia
- Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Rafael Rodrigues Lima
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém-Pará, Brazil
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Vazão AR, Claudino L, Pimpinato PP, Sampaio LV, Fiais GA, de Freitas RN, Justo MP, Brito VGB, Oliveira SHP, Lima RR, Cintra LTÂ, Chaves-Neto AH. Experimental apical periodontitis alters salivary biochemical composition and induces local redox state disturbances in the salivary glands of male rats. Clin Oral Investig 2024; 28:154. [PMID: 38366095 DOI: 10.1007/s00784-024-05540-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 01/31/2024] [Indexed: 02/18/2024]
Abstract
OBJECTIVES 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. MATERIALS AND METHODS Twenty 12-week-old male Wistar rats were randomly divided into two groups (n = 10): a control group and apical periodontitis group. After 28 days, 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. RESULTS 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. CONCLUSIONS 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. CLINICAL RELEVANCE Apical periodontitis could exacerbate the decline in oral health by triggering dysfunction in the salivary glands.
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Affiliation(s)
- Arieli Raymundo Vazão
- Programa de Pós-Graduação em Ciências, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
- Department of Basic Sciences, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Lívia Claudino
- Department of Basic Sciences, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Pedro Penati Pimpinato
- Department of Basic Sciences, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Larissa Victorino Sampaio
- Department of Basic Sciences, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
- Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas-SBFis, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Gabriela Alice Fiais
- Department of Basic Sciences, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
- Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas-SBFis, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Rayara Nogueira de Freitas
- Programa de Pós-Graduação em Ciências, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
- Department of Basic Sciences, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Mariana Pagliusi Justo
- Programa de Pós-Graduação em Ciências, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
- Department of Preventive and Restorative Dentistry, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Victor Gustavo Balera Brito
- Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas-SBFis, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Sandra Helena Penha Oliveira
- Department of Basic Sciences, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
- Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas-SBFis, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Rafael Rodrigues Lima
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Pará, Brazil
| | - Luciano Tavares Ângelo Cintra
- Programa de Pós-Graduação em Ciências, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
- Department of Preventive and Restorative Dentistry, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil
| | - Antonio Hernandes Chaves-Neto
- Programa de Pós-Graduação em Ciências, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil.
- Department of Basic Sciences, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil.
- Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas-SBFis, School of Dentistry of Araçatuba-UNESP-Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil.
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Sebring D, Kvist T, Lund H, Jonasson P, Lira-Junior R, Norhammar A, Rydén L, Buhlin K. Primary apical periodontitis correlates to elevated levels of interleukin-8 in a Swedish population: A report from the PAROKRANK study. Int Endod J 2024; 57:12-22. [PMID: 38290211 DOI: 10.1111/iej.13987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 09/27/2023] [Accepted: 09/28/2023] [Indexed: 02/01/2024]
Abstract
AIM To explore associations between root filled teeth, primary and secondary apical periodontitis, and levels of inflammatory markers in blood from patients with a first myocardial infarction and matched controls. METHODOLOGY Between May 2010 and February 2014, 805 patients with a first myocardial infarction and 805 controls, matched for sex, age, and postal code area, were recruited to the multicentre case-control study PAROKRANK (periodontitis and its relation to coronary artery disease). All participants underwent a physical and oral examination, as well as blood sampling. Using panoramic radiography, root filled teeth, primary apical periodontitis, and secondary apical periodontitis were assessed by three independent observers. Blood samples were analysed with enzyme-linked immunosorbent assay method for the following inflammatory markers: interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12p70, tumour necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Additionally, white blood cell count and plasma-fibrinogen were analysed. Associations between endodontic variables and the levels of inflammatory markers were statistically analysed with Mann-Whitney U-test and Spearman correlation, adjusted for confounding effects of baseline factors (sex, age, myocardial infarction, current smoking, diabetes, family history of cardiovascular disease, education, marital status, and periodontal disease). RESULTS Mean age of the cohort was 62 years, and 81% were males. Root fillings were present in 8.4% of the 39 978 examined teeth and were associated with higher levels of hsCRP, fibrinogen, and leukocyte count, but lower levels of IL-2 and IL-12p70. After adjusting for confounders, root filled teeth remained associated with higher levels of fibrinogen, but lower levels of IL-1β, IL-2, IL-6, and IL-12p70. Primary apical periodontitis was found in 1.2% of non-root filled teeth and associated with higher levels of IL-8 (correlation 0.06, p = .025). Secondary apical periodontitis was found in 29.6% of root filled teeth but did not relate to the levels of any of the inflammatory markers. CONCLUSIONS This study supports the notion that inflammation at the periapex is more than a local process and that systemic influences cannot be disregarded. Whether the observed alterations in plasma levels of inflammatory markers have any dismal effects on systemic health is presently unknown but, considering the present results, in demand of further investigation.
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Affiliation(s)
- Dan Sebring
- Department of Endodontology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Thomas Kvist
- Department of Endodontology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Henrik Lund
- Department of Oral Maxillofacial Radiology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Ronaldo Lira-Junior
- Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Anna Norhammar
- Unit of Cardiology, Department of Medicine, MedS Solna, Karolinska Institutet, Stockholm, Sweden
- Capio S:t Görans Hospital, Stockholm, Sweden
| | - Lars Rydén
- Unit of Cardiology, Department of Medicine, MedS Solna, Karolinska Institutet, Stockholm, Sweden
| | - Kåre Buhlin
- Unit of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden
- Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
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8
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Chauhan N, Mittal S, Tewari S, Sen J, Laller K. Effect of endodontic treatment on endothelial dysfunction and subclinical atherosclerosis-a prospective intervention study. Clin Oral Investig 2023; 27:5617-5625. [PMID: 37522992 DOI: 10.1007/s00784-023-05183-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 07/18/2023] [Indexed: 08/01/2023]
Abstract
OBJECTIVE The objective of this study is to investigate the effect of endodontic treatment on flow-mediated dilatation (FMD) and carotid intima-media thickness (c-IMT) in patients with apical periodontitis (AP). MATERIAL AND METHOD The study includes 32 young men having AP with a mean age of 25.78 years free from cardiovascular disease (CVD) and its risk factors, including periodontitis. All subjects underwent complete physical and dental examination, echocardiography, and ultrasound assessment of FMD on the brachial artery and c-IMT on the carotid artery at baseline and 12 months after the endodontic treatment. Data were analyzed using paired Student's t-test and Pearson's correlation coefficient (r) test using SPSS 26 version. RESULTS Endodontic treatment leads to the improvement of FMD significantly from a pooled baseline value of 4.84 ± 1.55% to 7.68 ± 2.08% (p < 0.05). The study also depicts a statistically significant difference between c-IMT (mean = 0.62 ± 0.11 mm) before treatment as compared to 12 months after treatment (mean = 0.59 ± 0.11 mm) (p < 0.05). CONCLUSION Endodontic treatment leads to improved FMD and decreased c-IMT suggesting that treating AP can be help revert the early stages of CVD. CLINICAL RELEVANCE AP could be a potential etiological factor of future CVD and should be treated as soon as diagnosed.
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Affiliation(s)
- Nishant Chauhan
- Post Graduate Institute of Dental Sciences, Rohtak, Haryana, 124001, India.
| | - Shweta Mittal
- Post Graduate Institute of Dental Sciences, Rohtak, Haryana, 124001, India
| | - Sanjay Tewari
- Post Graduate Institute of Dental Sciences, Rohtak, Haryana, 124001, India
| | - Jyotsna Sen
- Post Graduate Institute of Medical Sciences, Rohtak, Haryana, 124001, India
| | - Kuldip Laller
- Post Graduate Institute of Medical Sciences, Rohtak, Haryana, 124001, India
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Martos R, Tar I, Nagy AC, Csősz É, Kiss C, Márton I. Hypercitrullination and anti-citrullinated protein antibodies in chronic apical periodontitis, a laboratory investigation. Does autoimmunity contribute to the pathogenesis? Int Endod J 2023; 56:584-592. [PMID: 36762960 DOI: 10.1111/iej.13903] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/11/2023]
Abstract
AIM The presence of Gram-negative anaerobic bacteria, in particular, Porphyromonas gingivalis (P. gingivalis) in periapical granulomas predicts the generation of citrullinated proteins in the lesion. Citrullination of proteins may lead to the formation of anti-citrullinated autoantibodies (ACPA-s) initiating the formation of an autoimmune loop which may contribute to the perpetuation of inflammatory reactions and tissue damage in chronic apical periodontitis. The objective of this study was to demonstrate the formation of citrullinated proteins in chronic apical periodontitis and whether they can act as autoantigens. METHODOLOGY Twenty-five periapical granulomas (n = 25) were investigated in the study. Healthy periodontal tissue samples served as normal control tissue (n = 6). The peptidyl-citrulline level was determined with the dot blot method. ACPA levels were analysed using anti-citrullinated cyclic peptide (anti-CCP) EDIA kit. Differences between periapical granuloma and control samples were assessed using Mann-Whitney U tests. p Values <.05 were considered as statistically significant. RESULTS Protein concentrations, peptidyl-citrulline levels and anti-CCP ratios were compared between periapical granuloma and healthy control groups. Multiple linear regression analysis revealed significant (p = .042) hypercitrullination in periapical granuloma samples. Moreover, there was a significant difference in the ACPA ratios between periapical granuloma (2.03 ± 0.30) and healthy control (0.63 ± 0.17) groups (p = .01). Seventeen of 25 periapical granuloma samples (17/25; 68%), whereas one out of six control samples (1/6; 17%) were shown to be positive for the presence of ACPA. CONCLUSIONS This is the first study detecting the presence of citrullinated peptides and APCA in periapical granuloma, suggesting the contribution of autoimmune reactions in the pathogenesis and perpetuation of chronic apical periodontitis.
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Affiliation(s)
- Renáta Martos
- Department of Operative Dentistry and Endodontics, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
| | - Ildikó Tar
- Department of Oral Medicine, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
| | - Attila Csaba Nagy
- Department of Health Informatics, Faculty of Health Sciences, University of Debrecen, Debrecen, Hungary
| | - Éva Csősz
- Proteomics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Csongor Kiss
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Ildikó Márton
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.,Faculty of Health Sciences, University of Debrecen, Debrecen, Hungary
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10
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Georgiou AC, Cornejo Ulloa P, Van Kessel GMH, Crielaard W, Van der Waal SV. Reactive oxygen species can be traced locally and systemically in apical periodontitis: A systematic review. Arch Oral Biol 2021; 129:105167. [PMID: 34126418 DOI: 10.1016/j.archoralbio.2021.105167] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 05/17/2021] [Accepted: 05/25/2021] [Indexed: 12/22/2022]
Abstract
OBJECTIVES The aim of this systematic review was to summarize the existing evidence on the local production and systemic traces of reactive oxygen species (ROS) in apical periodontitis (AP). DESIGN A search of MEDLINE-PubMed and EMBASE was conducted up to January 12 of 2021 to identify studies in 6 different languages. Eligibility was evaluated and data were extracted from the eligible studies following the predefined objective. The Newcastle-Ottawa Scale was used for quality assessment of the included studies. RESULTS After screening, 21 papers met the inclusion criteria. Six studies were about systemic oxidative stress, 14 studies examined local production of reactive oxygen species and one studied both. ROS modulate cell signalling and cause oxidant imbalance locally at the site of AP. Cell signalling leads to a pro-inflammatory response, activation of MMPs and formation and progression of the AP lesion. Simultaneously, these oxidative stress biomarkers are also found in blood and saliva of subjects with AP. CONCLUSIONS Understanding the mechanism of ROS generation, involved in chronic inflammation, can provide us with important information to enhance local and systemic healing and possibly improve diagnostic tools. Future research considerations would be to use antioxidants to accelerate the return to oxidative balance.
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Affiliation(s)
- A C Georgiou
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands.
| | - P Cornejo Ulloa
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands
| | - G M H Van Kessel
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands
| | - W Crielaard
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands
| | - S V Van der Waal
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands; Department of Endodontics, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands
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11
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High-fat diet effect on periapical lesions and hepatic enzymatic antioxidant in rats. Life Sci 2020; 264:118637. [PMID: 33203524 DOI: 10.1016/j.lfs.2020.118637] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 10/17/2020] [Accepted: 10/19/2020] [Indexed: 12/11/2022]
Abstract
AIMS To evaluate the effects of a high-fat diet (HFD) on the progression of apical periodontitis (AP), local inflammation, systemic antioxidant status, and blood lipid profile in rats. MAIN METHODS Sixteen male Wistar rats were fed a standard diet (SD) or a HFD. At the sixth experimental week, the pulp chambers of the mandibular first molars were exposed to develop AP. A glucose tolerance test was performed the week before euthanasia. At the tenth experimental week, the animals were euthanized and the livers were collected to estimate catalase (CAT) and reduced glutathione (GSH) levels. Blood was acquired for biochemical analysis. The size of AP was estimated from radiographs and described as AP size-to-body weight ratio; inflammatory grade of AP was determined by histological analysis. KEY FINDINGS At the end of the experimental period, the rats fed the HFD had 30% less weight (P < 0.0001) and higher blood glucose levels after 30 min of sucrose intake (P < 0.05) than those fed the SD. Animals from the HFD group had lower levels of CAT (P < 0.01), but the same was not observed in the GSH levels. Plasma insulin and total cholesterol were not affected by the diet. The rats fed the HFD presented greater AP than those fed the SD (P < 0.05). However, the local inflammatory infiltrate was similar in both groups. SIGNIFICANCE The alterations promoted by the consumption of a HFD were not only observed systemically, but also locally, producing greater AP in rats than a SD.
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12
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Jiménez-Sánchez MC, Cabanillas-Balsera D, Areal-Quecuty V, Velasco-Ortega E, Martín-González J, Segura-Egea JJ. Cardiovascular diseases and apical periodontitis: association not always implies causality. Med Oral Patol Oral Cir Bucal 2020; 25:e652-e659. [PMID: 32388515 PMCID: PMC7473437 DOI: 10.4317/medoral.23665] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 03/02/2020] [Indexed: 12/19/2022] Open
Abstract
Background Several studies published in the last two decades have found an association between the prevalence of apical periodontitis (AP) or root canal treatment (RCT) and cardiovascular diseases (CVDs). However, the demonstration of association does not prove by itself the existence of a cause–effect relationship. Two diseases can appear as statistically related without any of them directly affecting the values of the other, resulting in a non-causal relationship. The aim of this narrative review is to summarize the current state of knowledge regarding the association between AP and CVDs, analysing it according to the Hill's causality criteria.
Material and Methods Epidemiological studies carried out on the association between CVDs and AP or RCT published in English until 8 December 2019 were identified. Forty-four articles were selected and its results were analysed.
Results Numerous cross-sectional epidemiological studies have found significant relationship between CVDs and AP. The odds ratio values range 1.6 - 5.4. However, other studies have not found significant association. Respect to RCT, some studies found correlation, but others found no association or even found that RCT is a protective factor against CVDs.
Conclusions The results are inconsistent and a causal relationship between CVDS and endodontic disease cannot be stablished. The risk factors common to both diseases can act as confounding factors, biasing the results. To reach definitive conclusions about the type of association (causal or non-causal) between both diseases, longitudinal epidemiological studies must be carried out to establish the temporal relationship and the dose-response gradient. Key words:Apical periodontitis, atherosclerosis, cardiovascular disease, coronary heart disease, endodontic medicine, root canal treatment.
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Affiliation(s)
- M-C Jiménez-Sánchez
- School of Dentistry, University of Sevilla C/ Avicena s/n, 41009-Sevilla, Spain
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13
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Apical periodontitis induces changes on oxidative stress parameters and increases Na +/K +-ATPase activity in adult rats. Arch Oral Biol 2020; 118:104849. [PMID: 32847752 DOI: 10.1016/j.archoralbio.2020.104849] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/01/2020] [Accepted: 07/21/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Endodontic infection can cause systemic alterations. The involvement of oxidative stress (OS) and transmembrane enzymes compose the pathogenesis of various systemic diseases. However, the relation among apical periodontitis (AP), OS parameters, and Na+/K+-ATPase (NKA) pump was not reported in the literature. This study evaluated the AP influence on OS parameters and NKA activity in adult rats. METHODS Adult male Wistar rats (sixteen weeks old) were randomly assigned to two experimental groups: control (CT group; n = 8) and AP (AP group; n = 9), which was induced in the first right mandibular molar tooth. After 21 days of AP induction, mandibles were dissected for radiographic analysis. In addition, the heart, liver, pancreas, and kidney were collected for analysis of endogenous OS parameters and NKA activity. Data were analyzed by Student's T-test. Values of p < 0.05 were considered statistically significant. RESULTS AP presence increased reactive species (RS) generation only in the heart, while the other analyzed organs did not have this parameter modified. Heart and pancreas had a decreased endogenous antioxidant system (catalase activity and vitamin C levels), liver and kidney had an increased one. AP increased NKA activity in the heart, liver, and pancreas, but not in the kidney. CONCLUSION The modulation of both endogenous antioxidant defense system and NKA activity in vital organs suggested that alterations in the antioxidant status and cellular electrochemical gradient may be involved in the AP pathophysiology.
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14
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Komatsu T, Kobayashi K, Morimoto Y, Helmerhorst E, Oppenheim F, Chang-Il Lee M. Direct evaluation of the antioxidant properties of salivary proline-rich proteins. J Clin Biochem Nutr 2020; 67:131-136. [PMID: 33041509 PMCID: PMC7533858 DOI: 10.3164/jcbn.19-75] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 11/10/2019] [Indexed: 01/20/2023] Open
Abstract
Proline-rich proteins are associated with the formation of an acquired protein layer overlying the tooth enamel surface. Previous studies have described the antioxidant activity of salivary histatin against the hydroxyl radical from Fenton’s reaction, acting as the critical reactive oxygen species. However, the role of proline-rich proteins in mitigating the oxidative stress caused by reactive oxygen species in the oral cavity remains unclear. In this study, we investigated the antioxidant effects of proline-rich proteins 2 on direct reactive oxygen species using electron spin resonance spectroscopy. For the first time, we demonstrated that proline-rich proteins 2 exhibits antioxidant activity directly against the hydroxyl radical produced by hydrogen peroxide with ultraviolet. Considering that identical results were obtained when assaying 30 residues of proline-rich proteins 2, the direct antioxidant effects against the hydroxyl radical by proline-rich proteins 2 may be related to these specific 30 residues.
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Affiliation(s)
- Tomoko Komatsu
- Division of Dentistry for the Special Patient, Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan.,Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Kyo Kobayashi
- Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Yoshinari Morimoto
- Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Eva Helmerhorst
- Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Albany street, Boston, MA 02118, USA
| | - Frank Oppenheim
- Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Albany street, Boston, MA 02118, USA
| | - Masaichi Chang-Il Lee
- Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
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15
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Jakovljevic A, Nikolic N, Carkic J, Beljic‐Ivanovic K, Soldatovic I, Miletic M, Andric M, Milasin J. Association of polymorphisms in TNF‐α, IL‐1β, GSTM and GSTT genes with apical periodontitis: is there a link with herpesviral infection? Int Endod J 2020; 53:895-904. [DOI: 10.1111/iej.13298] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 03/19/2020] [Indexed: 12/13/2022]
Affiliation(s)
- A. Jakovljevic
- Department of PathophysiologyUniversity of Belgrade BelgradeSerbia
| | - N. Nikolic
- Department of Human GeneticsUniversity of Belgrade BelgradeSerbia
| | - J. Carkic
- Department of Human GeneticsUniversity of Belgrade BelgradeSerbia
| | - K. Beljic‐Ivanovic
- Department of Restorative Dentistry and Endodontics School of Dental MedicineUniversity of Belgrade BelgradeSerbia
| | - I. Soldatovic
- Faculty of Medicine Institute of Medical Statistics and InformaticsUniversity of Belgrade BelgradeSerbia
| | - M. Miletic
- Department of PathophysiologyUniversity of Belgrade BelgradeSerbia
| | - M. Andric
- Department of Oral Surgery School of Dental Medicine University of Belgrade Belgrade Serbia
| | - J. Milasin
- Department of Human GeneticsUniversity of Belgrade BelgradeSerbia
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16
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Komatsu T, Kobayashi K, Helmerhorst E, Oppenheim F, Chang-Il Lee M. Direct assessment of the antioxidant property of salivary histatin. J Clin Biochem Nutr 2019; 65:217-222. [PMID: 31777423 PMCID: PMC6877405 DOI: 10.3164/jcbn.19-53] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 08/17/2019] [Indexed: 11/22/2022] Open
Abstract
Histatin, a salivary protein, affects oral homeostasis through preservation of tooth integrity and protection against caries and fungal infections. However, the effects of histatin in the generation of oxidative stress induced by reactive oxygen species and in the oral cavity remain unclear. In this study, the effects of histatin on direct reactive oxygen species scavenging activity were examined using electron spin resonance. We demonstrated, for the first time, that histatin exhibits antioxidant activity against hydroxyl radicals generated by Fenton's reaction by metal chelation or binding. The direct antioxidant effects of histatin, along with its antimicrobial activity, may be important in the oral protection of salivary proteins.
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Affiliation(s)
- Tomoko Komatsu
- Division of Dentistry for the Special Patient, Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan.,Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Kyo Kobayashi
- Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Eva Helmerhorst
- Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Albany street, Boston, MA 02118, USA
| | - Frank Oppenheim
- Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Albany street, Boston, MA 02118, USA
| | - Masaichi Chang-Il Lee
- Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
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17
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Georgiou AC, Crielaard W, Armenis I, de Vries R, van der Waal SV. Apical Periodontitis Is Associated with Elevated Concentrations of Inflammatory Mediators in Peripheral Blood: A Systematic Review and Meta-analysis. J Endod 2019; 45:1279-1295.e3. [PMID: 31542282 DOI: 10.1016/j.joen.2019.07.017] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 06/18/2019] [Accepted: 07/28/2019] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Apical periodontitis (AP), except for the local known consequences, may also be a systemic burden. Circulating inflammatory mediators that are released to sustain the AP lesion can in theory harm other bodily tissues. The aim of this systematic review was to summarize the existing evidence on the influence of AP on the peripheral blood levels of inflammatory mediators and markers of systemic stress. METHODS A search of MEDLINE-PubMed, Embase, and Cochrane was conducted up to and including February 2019 to identify studies in 5 different languages. The Newcastle-Ottawa Scale was used for quality assessment of the included studies. RESULTS Twelve of the 20 included studies were case-control studies, and 8 were intervention studies. The data of all the included studies were analyzed descriptively, whereas the data of 11 studies were available for meta-analyses. The study designs were heterogeneous. Nevertheless, the meta-analyses revealed statistically significant differences in C-reactive protein, interleukin 6, and asymmetric dimethylarginine levels between AP subjects and controls in peripheral blood. In addition, the concentration of C3 complement fragment in peripheral blood was significantly lower after the treatment and resolution of AP than before. CONCLUSIONS The existing literature indicates that AP adds on to systemic inflammation by elevating C-reactive protein, interleukin 6, asymmetric dimethylarginine, and C3 levels. In order to overcome the issue of large variation between study designs, future studies should have clear inclusion criteria, preferably larger cohorts, adequate follow-up of all subjects, and a thorough presentation of the data to enable further exploration of the possible burden of AP on general human health. Nevertheless, there is now stronger evidence that AP contributes to low-grade systemic inflammation.
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Affiliation(s)
- Athina Christina Georgiou
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Amsterdam, the Netherlands.
| | - Wim Crielaard
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Amsterdam, the Netherlands
| | - Iakovos Armenis
- Department of Cardiology, Onassis Cardiac Surgery Centre, Athens, Greece; Department of Internal Medicine, "Laiko" Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece
| | - Ralph de Vries
- Medical Library, Vrije Universiteit, Amsterdam, the Netherlands
| | - Suzette V van der Waal
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Amsterdam, the Netherlands; Department of Endodontics, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Amsterdam, the Netherlands
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18
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Jakovljevic A, Andric M, Nikolic N, Coric V, Krezovic S, Carkic J, Knezevic A, Beljic-Ivanovic K, Pljesa-Ercegovac M, Miletic M, Soldatovic I, Radosavljevic T, Jovanovic T, Simic T, Ivanovic V, Milasin J. Levels of oxidative stress biomarkers and bone resorption regulators in apical periodontitis lesions infected by Epstein-Barr virus. Int Endod J 2018; 51:593-604. [PMID: 29315650 DOI: 10.1111/iej.12886] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 01/04/2018] [Indexed: 02/05/2023]
Abstract
AIM To investigate whether apical periodontitis lesions infected by Epstein-Barr virus (EBV) exhibit higher levels of oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and oxidized glutathione (GSSG)] and bone resorption regulators [receptor activator of nuclear factor (NF-κB) ligand (RANKL) and osteoprotegerin (OPG)] compared to EBV-negative periapical lesions and healthy pulp tissues. METHODOLOGY The experimental group consisted of 30 EBV-positive and 30 EBV-negative periapical lesions collected in conjunction with apicoectomy. The pulp tissues of 20 impacted third molars were used as healthy controls. The qualitative and quantitative analysis of EBV was performed by nested and real-time polymerase chain reaction (PCR), respectively. The levels of RANKL and OPG were analysed by reverse transcriptase real-time PCR. The levels of 8-OHdG and GSSG were determined by enzyme-linked immunosorbent assay (ELISA). Mann-Whitney U-test and Spearman's correlation were used for statistical analysis. RESULTS The levels of RANKL, OPG, 8-OHdG and GSSG were significantly higher in apical periodontitis lesions compared to healthy pulp controls (P = 0.001, P < 0.001, P < 0.001 and P < 0.05, respectively). RANKL and OPG mRNA expression was significantly higher in EBV-positive compared to EBV-negative periapical lesions (P < 0.05). There was no significant correlation between EBV copy numbers and levels of RANKL, OPG, 8OH-dG and GSSG in apical periodontitis. CONCLUSION Levels of bone resorption regulators and oxidative stress biomarkers were increased in apical periodontitis compared to healthy pulp tissues. EBV-positive periapical lesions exhibited higher levels of RANKL and OPG compared to EBV-negative periapical lesions. EBV may contribute to progression of apical periodontitis via enhanced production of bone resorption regulators.
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Affiliation(s)
- A Jakovljevic
- Department of Pathophysiology, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
- Clinic of Oral Surgery, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - M Andric
- Clinic of Oral Surgery, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - N Nikolic
- Department of Biology and Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - V Coric
- Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - S Krezovic
- Clinic of Oral Surgery, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
- Department of Biology and Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - J Carkic
- Department of Biology and Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
- Department of Microbiology, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - A Knezevic
- Institute of Microbiology and Immunology, Department of Virology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - K Beljic-Ivanovic
- Clinic of Restorative Dentistry and Endodontics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - M Pljesa-Ercegovac
- Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - M Miletic
- Department of Pathophysiology, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - I Soldatovic
- Institute of Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - T Radosavljevic
- Institute of Pathophysiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - T Jovanovic
- Institute of Microbiology and Immunology, Department of Virology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - T Simic
- Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - V Ivanovic
- Clinic of Restorative Dentistry and Endodontics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - J Milasin
- Department of Biology and Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
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19
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Hernández-Ríos P, Pussinen PJ, Vernal R, Hernández M. Oxidative Stress in the Local and Systemic Events of Apical Periodontitis. Front Physiol 2017; 8:869. [PMID: 29163211 PMCID: PMC5672116 DOI: 10.3389/fphys.2017.00869] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 10/17/2017] [Indexed: 12/13/2022] Open
Abstract
Oxidative stress is involved in the pathogenesis of a variety of inflammatory disorders. Apical periodontitis (AP) usually results in the formation of an osteolytic apical lesion (AL) caused by the immune response to endodontic infection. Reactive oxygen species (ROS) produced by phagocytic cells in response to bacterial challenge represent an important host defense mechanism, but disturbed redox balance results in tissue injury. This mini review focuses on the role of oxidative stress in the local and associated systemic events in chronic apical periodontitis. During endodontic infection, ligation of Toll-like receptors (TLRs) on phagocytes' surface triggers activation, phagocytosis, synthesis of ROS, activation of humoral and cellular responses, and production of inflammatory mediators, such as, cytokines and matrix metalloproteinases (MMPs). The increment in ROS perturbs the normal redox balance and shifts cells into a state of oxidative stress. ROS induce molecular damage and disturbed redox signaling, that result in the loss of bone homeostasis, increased pro-inflammatory mediators, and MMP overexpression and activation, leading to apical tissue breakdown. On the other hand, oxidative stress has been strongly involved in the pathogenesis of atherosclerosis, where a chronic inflammatory process develops in the arterial wall. Chronic AP is associated with an increased risk of cardiovascular diseases (CVD) and especially atherogenesis. The potential mechanisms linking these diseases are also discussed.
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Affiliation(s)
- Patricia Hernández-Ríos
- Department of Conservative Dentistry, School of Dentistry, Universidad de Chile, Santiago, Chile
| | - Pirkko J Pussinen
- Oral and Maxillofacial Diseases, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Rolando Vernal
- Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.,Dentistry Unit, Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago, Chile
| | - Marcela Hernández
- Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.,Dentistry Unit, Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago, Chile
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20
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Vengerfeldt V, Mändar R, Saag M, Piir A, Kullisaar T. Oxidative stress in patients with endodontic pathologies. J Pain Res 2017; 10:2031-2040. [PMID: 28894386 PMCID: PMC5584906 DOI: 10.2147/jpr.s141366] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Apical periodontitis (AP) is an inflammatory disease affecting periradicular tissues. It is a widespread condition but its etiopathogenetic mechanisms have not been completely elucidated and the current treatment options are not always successful. PURPOSE To compare oxidative stress (OxS) levels in the saliva and the endodontium (root canal [RC] contents) in patients with different endodontic pathologies and in endodontically healthy subjects. PATIENTS AND METHODS The study group of this comparison study included 22 subjects with primary chronic apical periodontitis (pCAP), 26 with posttreatment or secondary chronic apical periodontitis (sCAP), eight with acute periapical abscess, 13 with irreversible pulpitis, and 17 healthy controls. Resting saliva samples were collected before clinical treatment. Pulp samples (remnants of the pulp, tooth tissue, and/or previous root filling material) were collected under strict aseptic conditions using the Hedström file. The samples were frozen to -80°C until analysis. OxS markers (myeloperoxidase [MPO], oxidative stress index [OSI], 8-isoprostanes [8-EPI]) were detected in the saliva and the endodontium. RESULTS The highest MPO and 8-EPI levels were seen in pCAP and pulpitis, while the highest levels of OSI were seen in pCAP and abscess patients, as well as the saliva of sCAP patients. Controls showed the lowest OxS levels in both RC contents and saliva. Significant positive correlations between OxS markers, periapical index, and pain were revealed. Patients with pain had significantly higher OxS levels in both the endodontium (MPO median 27.9 vs 72.6 ng/mg protein, p=0.004; OSI 6.0 vs 10.4, p<0.001; 8-EPI 50.0 vs 75.0 pg/mL, p<0.001) and saliva (MPO 34.2 vs 117.5 ng/mg protein, p<0.001; 8-EPI 50.0 vs 112.8 pg/mL, p<0.001) compared to pain-free subjects. CONCLUSION OxS is an important pathomechanism in endodontic pathologies that is evident at both the local (RC contents) and systemic (saliva) level. OxS is significantly associated with dental pain and bone destruction.
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Affiliation(s)
- Veiko Vengerfeldt
- Institute of Dental Sciences, Faculty of Medicine, University of Tartu
| | - Reet Mändar
- Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu
- Competence Centre on Health Technologies, Tartu, Estonia
| | - Mare Saag
- Institute of Dental Sciences, Faculty of Medicine, University of Tartu
| | - Anneli Piir
- Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu
| | - Tiiu Kullisaar
- Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu
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Cotti E, Zedda A, Deidda M, Piras A, Flore G, Ideo F, Madeddu C, Pau VM, Mercuro G. Endodontic Infection and Endothelial Dysfunction Are Associated with Different Mechanisms in Men and Women. J Endod 2015; 41:594-600. [DOI: 10.1016/j.joen.2015.01.037] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 01/27/2015] [Accepted: 01/30/2015] [Indexed: 10/23/2022]
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C-reactive protein expression is up-regulated in apical lesions of endodontic origin in association with interleukin-6. J Endod 2015; 41:464-9. [PMID: 25748492 DOI: 10.1016/j.joen.2014.12.021] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 12/14/2014] [Accepted: 12/15/2014] [Indexed: 02/02/2023]
Abstract
INTRODUCTION C-reactive protein (CRP) is the prototype component of acute-phase proteins induced ultimately by interleukin (IL)-6 in the liver, but it is unknown whether periradicular tissues locally express CRP. The present study aimed to identify whether CRP messenger RNA synthesis occurs in situ within apical lesions of endodontic origin (ALEOs) and healthy periodontal ligament and its association with IL-6 and to determine their protein levels and tissue localization. METHODS Patients with asymptomatic apical periodontitis and healthy volunteers presenting at the School of Dentistry, University of Chile, Santiago, Chile, were enrolled. ALEOs and healthy teeth were obtained and processed for either immunohistochemistry and double immunofluorescence to assess IL-6 and CRP tissue localization, whereas healthy periodontal ligaments were processed as controls for real-time reverse-transcription polymerase chain reaction for their RNA expression levels and multiplex assay to determine their protein levels. Statistic analysis was performed using the unpaired t test or Mann-Whitney test according to data distribution and Pearson correlation. RESULTS IL-6 and CRP were synthesized in ALEOs, whereas their RNA expression and protein levels were significantly higher when compared with healthy periodontal ligament. IL-6 and CRP immunolocalized to the inflammatory cells, vascular endothelial cells, and mesenchymal cells. Both, IL-6 and CRP colocalized in ALEOs, and a positive correlation was found between their expression levels (P < .05). CONCLUSIONS IL-6 and CRP messenger RNA are constitutively expressed in periodontal ligament and up-regulated in ALEOs along with higher protein levels. Given their pleiotropic effects, IL-6 and CRP protein levels in apical tissues might partially explain the development and progression of ALEOs as well as potentially asymptomatic apical periodontitis-associated systemic low-grade inflammation.
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Garrido M, Dezerega A, Castro-Martínez A, Hernández M. Host-derived biomarkers in gingival crevicular fluid for complementary diagnosis of apical periodontitis. World J Stomatol 2014; 3:19-24. [DOI: 10.5321/wjs.v3.i2.19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Revised: 05/07/2014] [Accepted: 05/14/2014] [Indexed: 02/07/2023] Open
Abstract
Apical periodontitis (AP) develops as a result of the host’s immune inflammatory response to pulpal infection of the dental root canals that leads to the generation of an apical lesion of endodontic origin (ALEO) and potentially to systemic metabolic alterations. Misdiagnosed ALEO is not infrequent due to the lack of diagnostic tools to differentiate apical lesions of different natures. Despite the conservative endodontic treatment shows a high success rate, there are refractory cases that can not be identified early enough during follow up. This evidences the need to develop complementary diagnostic tools, such as oral fluid biomarker analysis. Gingival crevicular fluid (GCF) is a serum transudate that becomes an exudate under inflammatory conditions, carrying molecules from local periodontal tissues and general circulation than can be harvested non-invasively. We aimed to review the available literature analyzing GCF composition in AP patients to evaluate whether GCF has any potential for complementary diagnosis. To the date, only few studies addressing changes of GCF components in AP are available. Most studies support GCF modifications in specific components in AP-affected teeth, suggesting that it might reflect periapical inflammation. GCF has potential for diagnostic tool, treatment follow-up and eventually to assess systemic comprise.
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Inchingolo F, Marrelli M, Annibali S, Cristalli MP, Dipalma G, Inchingolo AD, Palladino A, Inchingolo AM, Gargari M, Tatullo M. Influence of endodontic treatment on systemic oxidative stress. Int J Med Sci 2014; 11:1-6. [PMID: 24396280 PMCID: PMC3880985 DOI: 10.7150/ijms.6663] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2013] [Accepted: 08/26/2013] [Indexed: 01/24/2023] Open
Abstract
INTRODUCTION An increased production of oxidizing species related to reactive oral diseases, such as chronic apical periodontitis, could have systemic implications such as an increase in cardiovascular morbidity. Based on this consideration, we conducted a prospective study to assess whether subjects affected by chronic periodontitis presented with higher values of oxidative stress than reference values before endodontic treatment, and whether endodontic treatment can reduce the oxidative imbalance and bring it back to normal in these subjects. MATERIALS AND METHODS The authors recruited 2 groups of patients from private studies and dental clinics: these patients were recruited randomly. The oxidative balance in both patients with chronic apical periodontitis (CAP) and healthy control patients was determined by measuring the oxidant status, using an identification of the reactive oxygen metabolites (d-ROMs) test, while the antioxidant status in these patients was determined using a biological antioxidant potential (BAP) test. Both these tests were carried on plasma samples taken from enrolled patients. Values were measured both before the endodontic treatment of the patients with chronic apical periodontitis, and 30 and 90 days after treatment, and compared to those obtained from healthy control patients. RESULTS It was found that, on recruitment, the patients with chronic apical periodontitis exhibited significantly higher levels of oxidative stress than control patients, as determined by the d-ROMs and BAP tests. Furthermore, the d-ROMs test values were shown to decrease and the BAP test values to increase over time in patients with chronic apical periodontitis following endodontic therapy. As the levels of oxidative stress in these patients tended to reduce and return to normal by 90 days following treatment. CONCLUSIONS This study has demonstrated a positive association between chronic apical periodontitis and oxidative stress. Subjects affected by chronic apical periodontitis are exposed to a condition of oxidative stress, which is extremely dangerous to general health. Moreover, one can infer from these findings that through proper endodontic therapy, a good oxidative balance can be restored, thereby avoiding the risk of contracting the abovementioned diseases.
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Affiliation(s)
- Francesco Inchingolo
- 1. Department of interdisciplinary Medicine, University of Bari, General Hospital, Bari, Italy
| | - Massimo Marrelli
- 2. Unit of Maxillofacial Surgery, Calabrodental, Crotone, Italy; ; 4. Tecnologica Research Institute, Biomedical Section, Crotone, Italy
| | - Susanna Annibali
- 6. Department of Stomatology and Maxillofacial Science - Oral Surgery Unit - University of Rome "Sapienza" Rome, Italy
| | - Maria Paola Cristalli
- 6. Department of Stomatology and Maxillofacial Science - Oral Surgery Unit - University of Rome "Sapienza" Rome, Italy
| | - Gianna Dipalma
- 2. Unit of Maxillofacial Surgery, Calabrodental, Crotone, Italy
| | | | | | - Angelo Michele Inchingolo
- 5. Department of Surgical, Reconstructive, and Diagnostic Sciences, University of Milan, Milan, Italy
| | - Marco Gargari
- 8. Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Rome, Italy
| | - Marco Tatullo
- 2. Unit of Maxillofacial Surgery, Calabrodental, Crotone, Italy; ; 3. Department of Basic Medical Sciences, University of Bari, Bari, Italy; ; 4. Tecnologica Research Institute, Biomedical Section, Crotone, Italy
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Can Apical Periodontitis Modify Systemic Levels of Inflammatory Markers? A Systematic Review and Meta-analysis. J Endod 2013; 39:1205-17. [DOI: 10.1016/j.joen.2013.06.014] [Citation(s) in RCA: 122] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Revised: 04/29/2013] [Accepted: 06/29/2013] [Indexed: 01/01/2023]
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Dezerega A, Madrid S, Mundi V, Valenzuela MA, Garrido M, Paredes R, García-Sesnich J, Ortega AV, Gamonal J, Hernández M. Pro-oxidant status and matrix metalloproteinases in apical lesions and gingival crevicular fluid as potential biomarkers for asymptomatic apical periodontitis and endodontic treatment response. JOURNAL OF INFLAMMATION-LONDON 2012; 9:8. [PMID: 22436166 PMCID: PMC3358239 DOI: 10.1186/1476-9255-9-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2011] [Accepted: 03/21/2012] [Indexed: 01/22/2023]
Abstract
Background Oxidative stress and matrix metalloproteinases -9 and -2 are involved in periodontal breakdown, whereas gingival crevicular fluid has been reported to reflect apical status. The aim of this study was to characterize oxidant balance and activity levels of MMP -2 and -9 in apical lesions and healthy periodontal ligament; and second, to determine whether potential changes in oxidant balance were reflected in gingival crevicular fluid from asymptomatic apical periodontitis (AAP)-affected teeth at baseline and after endodontic treatment. Methods Patients with clinical diagnosis of AAP and healthy volunteers having indication of tooth extraction were recruited. Apical lesions and healthy periodontal ligaments, respectively, were homogenized or processed to obtain histological tissue sections. Matrix metalloproteinase -9 and -2 levels and/or activity were analyzed by Immunowestern blot, zymography and consecutive densitometric analysis, and their tissue localization was confirmed by immunohistochemistry. A second group of patients with AAP and indication of endodontic treatment was recruited. Gingival crevicular fluid was extracted from AAP-affected teeth at baseline, after endodontic treatment and healthy contralateral teeth. Total oxidant and antioxidant status were determined in homogenized tissue and GCF samples. Statistical analysis was performed using STATA v10 software with unpaired t test, Mann-Whitney test and Spearman's correlation. Results Activity of MMP-2 and MMP-9 along with oxidant status were higher in apical lesions (p < 0.05). Total oxidant status correlated positively with matrix metalloproteinase-2 and lesion size (p < 0.05). Gingival crevicular fluid showed significantly lower levels of total antioxidant status in diseased teeth at baseline compared to controls and endodontically-treated groups. Conclusions Apical lesions display an oxidant imbalance along with increased activity of matrix metalloproteinase-2 and -9 and might contribute to AAP progression. Oxidant imbalance can also be reflected in GCF from AAP-affected teeth and was restored to normal levels after conservative endodontic treatment. These mediators might be useful as potential biomarkers for chair-side complementary diagnostic of apical status in GCF.
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Affiliation(s)
- Andrea Dezerega
- Laboratorio de Biología Periodontal, Facultad de Odontología, Avenida Sergio Livingstone 943, Comuna de Independencia, Santiago, Chile.
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Graunaite I, Lodiene G, Maciulskiene V. Pathogenesis of apical periodontitis: a literature review. J Oral Maxillofac Res 2012; 2:e1. [PMID: 24421998 PMCID: PMC3886078 DOI: 10.5037/jomr.2011.2401] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2011] [Accepted: 09/03/2011] [Indexed: 05/29/2023]
Abstract
OBJECTIVES This review article discusses the host response in apical periodontitis with the main focus on cytokines, produced under this pathological condition and contributing to the degradation of periradicular tissues. The pace of research in this field has greatly accelerated in the last decade. Here we provide an analysis of studies published in this area during this period. MATERIAL AND METHODS Literature was selected through a search of PubMed electronic database. The keywords used for search were pathogenesis of apical periodontitis cytokines, periapical granuloma cytokines, inflammatory infiltrate apical periodontitis. The search was restricted to English language articles, published from 1999 to December 2010. Additionally, a manual search in the cytokine production, cytokine functions and periapical tissue destruction in the journals and books was performed. RESULTS In total, 97 literature sources were obtained and reviewed. The topics covered in this article include cellular composition of an inflammatory infiltrate in the periapical lesions, mechanisms of the formation of the innate and specific immune response. Studies which investigated cytokine secretion and functions were identified and cellular and molecular interactions in the course of apical periodontitis described. CONCLUSIONS The abundance and interactions of various inflammatory and anti-inflammatory molecules can influence and alter the state and progression of the disease. Therefore, periapical inflammatory response offers a model, suited for the study of many facets of pathogenesis, biocompatibility of different materials to periapical tissues and development of novel treatment methods, based on the regulation of cytokines expression.
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Affiliation(s)
- Indre Graunaite
- Department of Dental and Oral Pathology, Faculty of Odontology, Lithuanian University of Health SciencesLithuania.
| | - Greta Lodiene
- Department of Dental and Oral Pathology, Faculty of Odontology, Lithuanian University of Health SciencesLithuania.
| | - Vita Maciulskiene
- Department of Dental and Oral Pathology, Faculty of Odontology, Lithuanian University of Health SciencesLithuania.
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Cutando A, Gómez-Moreno G, Arana C, Acuña-Castroviejo D, Reiter RJ. Melatonin: potential functions in the oral cavity. J Periodontol 2007; 78:1094-102. [PMID: 17539724 DOI: 10.1902/jop.2007.060396] [Citation(s) in RCA: 86] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Melatonin is synthesized and secreted by the pineal gland and other organs. The pattern of melatonin secretion is controlled by an endogenous circadian timing system and conveys information about the light-dark cycle to the organism, thereby organizing its seasonal and circadian rhythms. Melatonin has powerful antioxidant effects, functions in an immunomodulatory role, may protect against certain cancers, delays some age-related processes, stimulates the synthesis of type I collagen fibers, and promotes bone formation. METHODS An extensive review was made (e.g., using PubMed, Science Direct, and Web of Knowledge) of the literature. RESULTS Melatonin, which is released into the saliva, may have important implications for dental disorders, especially in periodontal disease. Diseases of the periodontium are known to be aggravated by free radicals and by alterations in the immune response to microorganisms that are present in plaque. In response to periodontal inflammation, the blood and salivary levels of melatonin may increase. CONCLUSION Melatonin may play a role in protecting the oral cavity from tissue damage that is due to oxidative stress, and it may contribute to the regeneration of alveolar bone through the stimulation of type I collagen fiber production and the modulation of osteoblastic and osteoclastic activity.
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Affiliation(s)
- Antonio Cutando
- Department of Special Care in Dentistry, School of Dentistry, University of Granada, Granada, Spain.
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Cutando A, Gomez-Moreno G, Arana C, Escames G, Acuña-Castroviejo D. Melatonin reduces oxidative stress because of tooth removal. J Pineal Res 2007; 42:419-20. [PMID: 17439559 DOI: 10.1111/j.1600-079x.2007.00425.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Cutando A, Arana C, Gómez-Moreno G, Escames G, López A, Ferrera MJ, Reiter RJ, Acuña-Castroviejo D. Local Application of Melatonin Into Alveolar Sockets of Beagle Dogs Reduces Tooth Removal–Induced Oxidative Stress. J Periodontol 2007; 78:576-83. [PMID: 17335383 DOI: 10.1902/jop.2007.060244] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The antioxidant and anti-inflammatory hormone melatonin is secreted by saliva into the oral cavity, where it may protect the mucosal and gingival tissues from radical damage. To date, no studies have addressed the potential beneficial role of melatonin in the acute inflammatory response that follows oral surgical interventions, especially tooth extractions. The aim of this study was to determine whether tooth extraction induces changes in plasma oxidative stress levels, and whether melatonin treatment may counteract these changes. METHODS Maxillary and mandibular premolars and molars of 16 adult Beagle dogs were extracted under general anesthesia. Eight dogs were treated with 2 mg melatonin placed into the alveolar sockets, whereas the other eight dogs received only vehicle. Lipid peroxidation (LPO) and nitrite plus nitrate (NOx) levels were determined in plasma, whereas glutathione (GSH) and glutathione disulfide (GSSG) levels and glutathione peroxidase (GPx) and reductase (GRd) activities were measured in red blood cells before and 24 hours after tooth extraction. RESULTS Removal of the premolars and molars caused a significant rise in plasma LPO and NOx levels and in the erythrocyte GSSG/GSH ratio, whereas melatonin treatment restored the normal values of these parameters. Also, melatonin slightly increased erythrocyte GRd activity without changing GPx activity. CONCLUSION For the first time to our knowledge, the results show that during the immediate postoperative period following tooth extraction, there is a significant increase of oxidative stress, which is counteracted by the administration of melatonin into the alveolar sockets.
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Affiliation(s)
- Antonio Cutando
- Department of Special Care in Dentistry, School of Dentistry, University of Granada, Granada, Spain
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