Integrative Computational and Experimental Approaches Reveal the Protective Role of Moderate Caffeine Intake Against Apical Periodontitis Induced Bone Loss.

Abstract

AIM: To investigate whether moderate systemic caffeine intake modulates the progression of apical periodontitis (AP) and associated alveolar bone loss, combining in&#xa0;vivo rat experiments with in silico molecular docking to explore potential mechanisms. METHODOLOGY: Male Wistar rats were randomly assigned to four groups (n&#x2009;=&#x2009;8 per group): control, caffeine, AP, AP&#x2009;+&#x2009;caffeine. AP was induced by pulp exposure of mandibular first molars and allowed to develop for 28&#x2009;days. Animals in caffeine groups received 10&#x2009;mg/kg/day by orogastric gavage during the experimental period. The antioxidant capacity of caffeine was assessed by DPPH&#x2022; and ABTS&#x2022;&#x2009;+&#x2009;assays. Systemic oxidative status was evaluated by blood reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). Histology, Picro-Sirius red staining for collagen, and micro-computed tomography (micro-CT) analysis of alveolar bone (BV/TV, Tb.N, Tb.Sp, porosity, lesion volume) were performed. Molecular docking against adenosine Aand Areceptors was used to probe caffeine-receptor interactions. RESULTS: Caffeine showed relevant radical-scavenging activity in&#xa0;vitro (DPPH&#x2022; assay). AP induced systemic redox imbalance, marked inflammatory infiltration, collagen loss and increased lesion volume. Moderate caffeine intake restored redox markers (&#x2191;GSH, &#x2193;TBARS), attenuated inflammatory infiltrate, preserved collagen content and reduced lesion volume (AP&#x2009;+&#x2009;caffeine vs. AP; p&#x2009;<&#x2009;0.05). Micro-CT demonstrated improved alveolar bone microarchitecture in AP&#x2009;+&#x2009;caffeine group (increased BV/TV and Tb.N; reduced Tb.Sp and porosity). Molecular docking indicated stable hydrophobic and hydrogen-bond interactions of caffeine within Aand Areceptor binding pockets, supporting an antagonistic effect on adenosine signalling consistent with reduced pro-inflammatory activation. CONCLUSION: Moderate systemic caffeine (10&#x2009;mg/kg/day) attenuates apical periodontitis progression and preserves alveolar bone quality in rats, associated with antioxidant activity and a probable modulation of adenosine receptor-mediated inflammatory pathways.