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The alcohol groups were exposed to self\u2010administration of a 25% alcohol solution, while the other groups were given only filtered water. The nicotine groups received daily intraperitoneal injections of a nicotine solution (0.19\u2009\u03bcL of nicotine\/mL), whereas the other groups received saline solution. Periapical lesions were induced by exposing the pulps of the left mandibular first molars for 28\u2009days. After euthanasia, the mandibles were removed and the percentage bone volume, bone mineral density, trabecular thickness, trabecular separation and trabecular number of the periapical bone were measured using micro\u2010computed tomography images. Serum samples were collected for analysis of proinflammatory cytokines (IL\u20101\u03b2, IL\u20104, IL\u20106 and TNF\u2010\u03b1), biochemical and metabolomic analysis. Statistical analysis was performed with a significance level of 5%. Nonparametric data were analysed using the Kruskal\u2010Wallis test followed by Dunn's test, while one\u2010way <jats:sc>anova<\/jats:sc> followed by Tukey's test was performed for parametric data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The groups exposed to alcohol or nicotine consumption exhibited an altered bone pattern indicating lower bone density and higher levels of IL\u20101\u03b2, IL\u20106 and TNF\u2010\u03b1 compared to the Control group (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). Significant differences were observed among the groups in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholesterol, triglycerides, urea, creatinine, albumin, uric acid, bilirubin and calcium. Metabolomic analysis revealed significant differences in glycine, phosphocholine, lysine, lactate, valine, pyruvate and lipids (CH<jats:sub>2<\/jats:sub>CH<jats:sub>2<\/jats:sub>CO), n(CH<jats:sub>2<\/jats:sub>) and n(CH<jats:sub>3<\/jats:sub>). Most of these parameters were even more altered in the simultaneous consumption of both substances compared to single consumption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Alcohol and nicotine chronic consumption altered several metabolic markers, impaired liver and kidney function, increased the production of systemic proinflammatory mediators and harmed the periapical bone microarchitecture in the presence of apical periodontitis. The simultaneous consumption of alcohol and nicotine intensified these detrimental effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.13994","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T21:33:42Z","timestamp":1700084022000},"page":"178-194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Chronic alcohol and nicotine consumption as catalyst for systemic inflammatory storm and bone destruction in apical periodontitis"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5642-9541","authenticated-orcid":false,"given":"Karem Paula","family":"Pinto","sequence":"first","affiliation":[{"name":"Department of Integrated Clinical Procedures, School of Dentistry Rio de Janeiro State University (UERJ)  Rio de Janeiro 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