Fluoxetine Inhibits Inflammatory Response and Bone Loss in a Rat Model of Ligature‐Induced Periodontitis

Abstract

Background Fluoxetine, a selective serotonin reuptake inhibitor, has recently been found to possess anti-inflammatory properties. The present study investigated the effects of fluoxetine on inflammatory tissue destruction in a rat model of ligature-induced periodontitis (PD). Methods Male Wistar rats were randomly assigned into three groups (n=10 animals/group): 1) Control rats (without ligature); 2) rats with ligature + placebo (saline; oral gavage); 3) rats with ligature + fluoxetine (20 mg/kg/day in saline; oral gavage). Histological analyses were performed on the furcation region and mesial of mandibular first molars of rats sacrificed at 15 days after ligature-induced PD. Reverse transcriptase-polymerase chain reaction (RT-PCR) and zymography were performed to analyze the mRNA expression of interleukin (IL)-1β, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS), and the MMP-9 activity, respectively, in gingival tissues samples. Results Compared to the ligature + placebo group, alveolar bone loss was reduced in the fluoxetine group (P < 0.05), and the integrity of collagen fibers in the gingival tissue was maintained. Moreover, in gingival tissue sampled 3 days after ligature attachment, fluoxetine administration reduced IL-1β and COX-2 mRNA expression. Fluoxetine down-regulated MMP-9 activity, without affecting MMP-9 mRNA expression induced by ligature, compared to the ligature + placebo group (P < 0.05). These data suggested that fluoxetine suppressed proinflammatory responses, as well as proteolytic enzyme activity, induced by ligature. Conclusions In the present study, fluoxetine suppressed the inflammatory response and protected against periodontal bone resorption and destruction of collagen fibers, suggesting that fluoxetine can constitute a promising therapeutic approach for periodontal diseases.

Effects of treatment with fluoxetine on mandibular development: A morphological study in rats

“…The same result was found by Branco-de-Almeida et al (2012) studying the influence of fluoxetine on the periodontium, showing that this substance may interfere in the quality of the bone matrix formed. However, the result found by these authors refers to the alveolar bone and not to the mandibular bone.…”

Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages

“…These effects were shown to be due to direct actions of the drug on macrophages, as well as indirectly via neuroendocrine mechanisms [33]. Because of these various effects of SSRIs on inflammation, studies have also looked at the role of SSRIs in mouse models of experimental colitis [9], arthritis[11], periodontitis [10] and also in facilitating wound healing [34]. More recently, paroxetine has also been shown to possess anti-inflammatory properties in neuro-inflammation models relevant in Parkinson's disease [8].…”

“…In this regard, SSRIs have been reported to have anti-inflammatory properties in not only neuronal tissues but also in non-neuronal cells [6,7]. In animal models of disease, SSRIs are able to effectively modulate neuronal as well as non-neuronal inflammatory diseases [8-10]. Given that paroxetine and fluoxetine are already FDA approved, there is also interest in repurposing these drugs possibly as anti-inflammatory therapeutics for diseases such as arthritis and colitis [11,12].…”

Nanoemulgel (NEG) of Ketoprofen with eugenol as oil phase for the treatment of ligature-induced experimental periodontitis in Wistar rats

“…To induce periodontitis, 18 rats (180-210 g) were initially anesthetized with an intramuscular injection (i.m.) of ketamine (90 mg/kg) and xylazine (10 mg/kg) (Branco-de-Almeida et al, 2012). Experimental periodontitis were induced by the placement of a non-absorbable sterile surgical silk ligature 3/0 (Ethicon, Johnson & Johnson LTD., Baddi, Himachal Pradesh, India) around the gingival crevices of the first left lower molar teeth utilizing the procedure used by Györfi et al (1994) with some modification (Xu & Wei, 2006).…”