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Can Wine Modulate Apical Periodontitis Inflammation?

João Eduardo Gomes-Filho*

Department of Dentistry, University of State of Sao Paulo, Arcatuba, Brazil

*Corresponding Author:
João Eduardo Gomes-Filho
Department of Dentistry,
University of State of Sao Paulo, Arcatuba, Brazil
E-mail: [email protected]

Received: 21-Jan-2022, Manuscript No,JDS-22-51970; Editor assigned: 24-Jan-2022, Manuscript No,JDS-22-51970 (PQ); Reviewed: 07-Feb-2022, QC No. JDS-22-51970; Accepted: 10-Feb-2022, QC No. JDS22-51970 Published: 15-Feb-2022, DOI: 10.4172/2320-7949.10.2.005.

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There are a substantial number of studies suggesting possible benefits of the moderate wine consumption on human health. By the other side, it is known that chronic excessive alcohol consumption has a negative impact on bone health and in many organs. However, epidemiological evidence suggests that moderate consumption of alcoholic beverages may have beneficial effects on bone tissue. This mini-review aims to explore the relationship of wine and apical periodontitis inflammation.


Periodontitis; Resveratrol; Odontoclasts; Quercetin; Cementum


Apical periodontitis is the product resulting from persistent bacterial contamination of the root canal system in the face of combat led by the host's immune system, characterized by an inflammation of periradicular tissues [1]. When the dental pulp becomes infected, bacteria and their byproducts evoke nonspecific inflammatory responses, as well as specific immunological reactions, leading to the destruction of bone by osteoclasts and resorption of dental hard tissues (cementum and dentin) by multinucleated cells designated as odontoclasts [2,3]. Red wine and the isolated polyphenols (resveratrol and quercetin) have been established to alter the functioning of bone tissue and the immune system, both crucial elements for the development of apical periodontitis [4-10].

This mini-review aims to expose some scientific information regarding the effects of red wine on the development of apical periodontitis.


The wine Wine consumption is a common habit throughout the world [11]. Wine is an alcoholic beverage popularly produced from fermented grape juice. Wines can be classified as red, rose (pink), or white based on their color, and they can also be classified as table (red, rose, or white), sparkling, or fortified based on their alcohol level or carbon dioxide content [12]. Table wines are wines that are neither fortified nor sparkling and are typically served with food; fortified wines are made by adding alcohol [13,14]. Wines can also be classified based on how much carbon dioxide they contain. Those that contain carbon dioxide are classified as sparkling wines or “still” wines [12,13]. Wines can also be classified as alcohol free (<0.5% v/v), low-alcohol (0.5% to 1.2% v/v), reduced-alcohol (1.2% to 5.5% or 6.5% v/v), lower-alcohol (5.5% to 10.5% v/v), and alcoholic wines (>10.5% v/v) [15,16]. In addition, wines are also classified according to their sugar content: dry (maximum of 4 g/L sugar), medium dry (between 4 g/L and 12 g/L sugar), semi-sweet (between 12 g/L and 45 g/L sugar), and sweet (minimum of 45 g/L sugar) [17]. These classifications may vary between countries and their legislations.

Wine is composed of water, ethanol, glycerol, polysaccharides, and different types of acids and, in addition, presents a complex mixture of bioactive compounds that are predominantly phenolic in nature [18]. It is one of the main sources of polyphenols through the diet; like that, drinkers red wine moderates consume polyphenols at levels well above the average of the 4 population [19]. The phenolic compounds in wine can be divided into flavonoids and non-flavonoids. Flavonoids represent more than 85% of the components phenolics in red wine, including different molecular families such as flavonols (quercetin), flavones and anthocyanidins. Non-flavonoid compounds include acids hydroxycinnamics, hydroxybenzoic acids, stilbenes and its derivative, resveratrol [20].

Wine and systemic health It is estimated that the medicinal use of wine dates back to 2200 BC [21]. In the early 1990s, the discovery of the "French paradox" was reported, popularizing the Health benefits of red wine. This term was designed to describe the relationship inverse between coronary heart disease mortality and red wine consumption observed in French. This has been attributed to the so-called "Mediterranean diet", which includes an intake of constant wine [22]. Twenty years after the formulation of this concept, there have been a substantial number of studies suggesting possible benefits for the health that moderate wine consumption has on human health [23]. By the other side, it is known that chronic excessive alcohol consumption has a negative impact on bone health, in addition to deleterious effects on many organs. However, epidemiological evidence suggests that moderate consumption of alcoholic beverages may have beneficial effects on bone tissue [22].

Moderate consumption of alcohol has a positive impact on the immune system compared to excessive alcohol, also presenting an anti-inflammatory effect [24]. In vitro studies have shown that exposure to moderate doses of alcohol can inhibit the activation of NF-kB in human monocytes [25]. In addition, it was also reported that light alcohol consumption, preferably wine, resulted in an increase in bone mineral density of the spine and of the whole body in postmenopausal women [26]. In general, the beneficial effect of regular and moderate consumption of wine is obtained with approximately 150 ml/day for women and 300 ml/day for men [27,28].

There is evidence that ethanol increases the risk of cancer in the oral cavity, pharynx, larynx, esophagus and liver [29,30]. However it is possible that polyphenols and other potentially protective compounds present in wine may counteract the harm associated with ethanol.

It has been shown that red wine also promotes bone formation and prevents bone loss, inducing the proliferation of osteoblasts and inhibiting the differentiation of osteoclasts and, consequently, bone resorption. These mechanisms include the differentiation and proliferation of osteoblasts by mechanisms mediated by Receptors Estrogen (ER), activation of kinase 1/2 (ERK 1/2) and regulation of extracellular Wnt signal, increased osteoclast apoptosis and inhibition of factor activating receptor (RANKL) nuclear KB ligand [31-33].

Wine and apical periodontitis Recently our group investigated the effects of red wine on the development of apical periodontitis in a rat model study and we observed that red wine decreases the inflammatory intensity, the marking of TRAP in the periapical lesion, while the administration of isolated Resveratrol/Quercetin increased the expression of OPG and IL-10, in addition to decreasing TRAP [34]. One possibility to explain the attenuation of the beneficial effects of wine may be related to the presence of alcohol, as we observed a negative effect of alcohol on the development of periapical lesions when in concentrations above 15% [35].

The pathogenesis of the apical periodontitis is related to inflammation and immune responses promoting bone resorption in the apical region [36]. When the periapical lesion is installed, inflammatory cytokines or interleukins play an important role in the immune response, initiating and coordinating cellular events and regulating the host's response to endotoxins. Furthermore, the bone resorption that occurs in these pathologies appears as a determining factor for the expansion of these lesions, being initiated by the proliferation of immature osteoclast precursor cells and their differentiation into mature osteoclastic cells that promote the degradation of organic and inorganic bone components. RANKL is a key molecule in osteoclast activation and OPG is a receptor for RANKL. The increase in RANKL/OPG rate favors bone resorption through osteoclastogenesis and osteoclast activation [37]. The beneficial effect of resveratrol consumption in reducing alveolar bone loss seems to be associated with the modulation of the host's immune-inflammatory reaction, as indicated by other studies using different experimental models. The modulatory action exerted by resveratrol seems to be attributed to its inhibitory effect on the production of pro-inflammatory cytokines of the Th17 immune response, as the administration of this natural agent promoted a significant reduction in IL-17 levels [38,39].

Similarly to the observation regarding the apical periodontitis, periodontal disease is also benefited with wine or its phenolic compounds administration in different study models. A prospective cohort study found that intake of wine is inversely associated with clinical attachment loss in men [40]. It was also evidenced a beneficial effect of wine on periodontal status of southern Brazilian adults [41]. In animals, periodontitis was down regulated with the use of the polyphenols present in the red wine once continuous administration of resveratrol decreased periodontal breakdown induced experimentally in rats [42]. Moreover, resveratrol administered to rats caused a significant reduction in bone resorption [43]. Even when administrated subcutaneously it protected rats from periodontal tissue damage by inhibiting inflammatory responses and by stimulating antioxidant defense systems [44]. The same results observed when administered freely in drinking water [45]. Moreover, resveratrol decreased periodontal breakdown during smoking in rats [46].

Quercetin also could exhibit protective effects in bacterial-induced periodontitis, reducing the alveolar bone loss by mechanisms involving the reduction of pro-inflammatory cytokine production and down-regulation of the osteoclastogenic cytokine RANKL [47]. In addition, it could reduce alveolar bone loss in ligature-induced periodontitis by increasing osteoblastic activity, decreasing osteoclastic activity, apoptosis, and inflammation [48]. This flavonoid has been reported to decrease osteoclastogenesis via inhibition of the activating nuclear factor-kB ligand receptor (RANKL), involved in osteoclastic differentiation; can directly induce apoptosis of mature osteoclasts; and furthermore, the local use of quercetin in a collagen matrix caused greater new bone formation [49, 50]. 6 Quercetin is able to increase Alkaline Phosphatase (ALP) activity in osteoblasts of the MG-63 lineage; the quercetin-supplemented diet can also reverse osteopenia in diabetic rats as well as inhibit bone loss in ovariectomized mice, confirming its beneficial effect on bone tissue in bone disorders [51-54].


This review spotlights a promising approach using the red wine or its phenolic compounds to modulate the inflammation during the periapical periodontitis development. Although numerous studies have looked at a wide range of molecules in the context of AP, the involvement of TLR2, MyD88, MMP2, and MMP9 in the spread of infection, pulpal necrosis, and AP development is still unknown. Our research revealed some new details about the chemicals involved in the evolution of AP. However, further research in animals and humans is needed to better understand the relationship between bacteria, MMPs, and the innate immune system.