The influence of adrenergic blockade in rats with apical periodontitis under chronic stress conditions

The influence of adrenergic blockade in rats with apical periodontitis under chronic stress conditions:

Publication date: Available online 20 October 2019

Source: Archives of Oral Biology

Author(s): Rayana Duarte Khoury, Renata Falchete do Prado, Felipe de Souza Matos, Bruna Ribas de Meireles, Flávia Goulart da Rosa Cardoso, Luciane Dias de Oliveira, Cláudio Antonio Talge Carvalho, Marcia Carneiro Valera

Abstract

Objective

To investigate the influence of chronic stress and adrenergic blockade in a rat model of apical periodontitis.

Methods

Thirty-two Wistar rats were submitted to an animal model of periapical lesion and randomly divided into 4 groups (n = 8): no stress (NS); stress + saline solution (SS); stress + β-adrenergic blocker (Sβ); stress + α-adrenergic blocker (Sα). The SS, Sβ and Sα groups were submitted to an animal model of chronic stress for 28 days and received daily injections of saline solution, propranolol (β adrenergic blocker) and phentolamine (α adrenergic blocker), respectively. After 28 days the animals were euthanized and the following analyses were carried out: a) serum corticosterone levels through Radioimmunoassay; b) measurement of serum levels of IL-1B, IL-6, IL-10 and IL-17 by enzyme-linked immunosorbent assay (ELISA); c) volume of periapical bone resorption by micro-computed tomography; d) histomorphometric analysis by staining with hematoxylin and eosin; e) expression of β-AR, α-AR, receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) by immunohistochemistry; f) tartrate-resistant acid phosphatase (TRAP) staining; g)ex-vivo cytokine release followed by the stimulation with LPS in superfusion system, by ELISA.

Results

SS group displayed significantly higher corticosterone levels than NS group (non-stressed). Higher IL-1β serum level was observed in the NS group (p < .05); compared to all stressed groups. Other cytokines were present in similar amounts in the serum of all groups. All groups presented similar periapical lesions. All groups presented moderate inflammatory infiltrate, without statistically significant differences between them. No differences were observed regarding β-AR, α-AR, Rank-L and OPG expression. The number of TRAP-positive cells was significantly decreased in the groups that received daily injections of adrenergic blockers. The IL-1β release followed LPS stimulation was significantly suppressed when the superfusion media contained propranolol (p < .05). Perfusion containing phentolamine induced a greater release of IL-10. TGF-β was significantly suppressed by phentolamine perfusion in the NS group (p < .05).

Conclusions

Chronic stress can significantly change the inflammatory cytokines release. Rank-L/OPG system and periapical lesion volume were not affected following the current method applied. The administration of adrenergic blockers was not able to modulate the inflammatory response but presented effectivity in reducing the number of osteoclasts in the periapical region.

Graphical Abstract

Prolonged activation of the HPAA and the SNS caused by long-term exposure to stress, causes the release of catecholamines and glucocorticoids which leads to detrimental effects on immune functions. The high levels of stress hormones may supress the immune system by inhibiting antibodies, disrupting the T-helper/T-suppressor balance and natural killer cell function, changing inflammatory cytokine imbalance. Chronic stress deregulates the immune response by altering the balance of type 1 cytokines (inflammatory) towards type 2 cytokine (suppressor) mediated responses. Therefore, the combination of a greater tendency to inflammation and a depressed immunity has led to the general acceptance that chronic psychological stress represents a potential cofactor in the pathogenesis of many chronic diseases, including periodontitis.