{"title":"Systemic administration of propranolol reduces bone resorption and inflammation in apical periodontitis of chronically stressed rats","authors":"Rayana Duarte Khoury, Giovanna Bignoto Minhoto, Patricia Pimentel de Barros, Juliana Campos Junqueira, Carolina Fedel Gagliardi, Renata Falchete do Prado, Marcia Carneiro Valera","doi":"10.1111/iej.14118","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aim</h3>\n \n <p>To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats.</p>\n </section>\n \n <section>\n \n <h3> Methodology</h3>\n \n <p>Twenty-four 70-day-old male Wistar rats (<i>Rattus norvegicus</i>, <i>albinus</i>) were distributed into three groups (<i>n</i> = 8): rats with AP without stressful conditions (AP-Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT-PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one-way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal–Wallis followed by Dunn's test. Significance level was set at 5% (<i>p</i> < .05) for all assessed parameters.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Micro-CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (<i>p</i> < .05), but no differences were observed between the Control and AP + S + PRO groups (<i>p</i> > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (<i>p</i> < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (<i>p</i> < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (<i>p</i> < .05).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti-inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms.</p>\n </section>\n </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International endodontic journal","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/iej.14118","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Aim
To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats.
Methodology
Twenty-four 70-day-old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP-Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT-PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one-way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal–Wallis followed by Dunn's test. Significance level was set at 5% (p < .05) for all assessed parameters.
Results
Micro-CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p < .05), but no differences were observed between the Control and AP + S + PRO groups (p > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p < .05).
Conclusions
Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti-inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms.
目的:评估全身给药普萘洛尔对慢性应激大鼠根尖牙周炎(AP)严重程度的影响:将24只70天大的雄性Wistar大鼠(Rattus norvegicus, albinus)分为三组(n = 8):无应激条件下患有牙尖周炎的大鼠(AP-对照组)、患有牙尖周炎并接受慢性不可预测应激(CUS)方案治疗的大鼠(AP + S组)和患有牙尖周炎并接受普萘洛尔治疗的CUS方案治疗的大鼠(AP + S + PRO组)。应激过程每天进行,直到实验结束。CUS 3 周后,将下颌和上颌第一磨牙的牙髓组织暴露于口腔环境中,诱发所有组的 AP。在整个实验期间,每天口服一次普萘洛尔。大鼠在42天时被处死,并采集血液通过多重分析法检测应激生物标志物血清剂量。取出大鼠下颌骨,进行显微断层扫描和组织病理学分析。将上第一磨牙周围的根尖周组织匀浆并进行 RT-PCR 分析,以评估 RANKL、TRAP 和 OPG 的 mRNA 表达。参数数据采用单因素方差分析,然后进行Tukey检验;非参数数据采用Kruskal-Wallis分析,然后进行Dunn检验。显著性水平设定为 5%(P 结果:显微 CT 显示,AP + S 组的骨吸收率更高(p .05),差异有统计学意义。与 AP + S 组相比,AP + S + PRO 组的炎症浸润强度和程度较低,骨质流失面积较小(P 结论:AP + S + PRO 组的骨质流失面积较小(P.05):口服普萘洛尔对应激大鼠的 AP 严重程度有显著影响,这表明普萘洛尔具有抗炎作用,对应激动物 AP 的骨吸收具有保护作用。有必要开展进一步研究,以全面了解其潜在机制。
期刊介绍:
The International Endodontic Journal is published monthly and strives to publish original articles of the highest quality to disseminate scientific and clinical knowledge; all manuscripts are subjected to peer review. Original scientific articles are published in the areas of biomedical science, applied materials science, bioengineering, epidemiology and social science relevant to endodontic disease and its management, and to the restoration of root-treated teeth. In addition, review articles, reports of clinical cases, book reviews, summaries and abstracts of scientific meetings and news items are accepted.
The International Endodontic Journal is essential reading for general dental practitioners, specialist endodontists, research, scientists and dental teachers.