Safety of Topical Resolvin E1 Treatment in Experimental Periodontitis

BACKGROUND: Resolvin E1 (RvE1) is a potent proresolving mediator of inflammation that is biosynthesized from the omega-3 eicosapentaenoic acid (EPA). In a rabbit model of human periodontal disease, topical RvE1 resulted in complete resolution of inflammation and regeneration of alveolar bone. AIM: To evaluate the safety of topical RvE1 treatment in systemic tissues of rabbits. METHODS: Periodontitis was induced with ligature and Porphyromonas gingivalis in New Zealand white rabbits for a 6-week period and animals were randomized into untreated (n=5); vehicle (n=5); or RvE1 (n=14) groups with topical delivery every-other-day for 6 weeks. After sacrifice, the internal organs (lung, kidney, liver, spleen, heart) were fixed in formalin, paraffin-embedded, sectioned, and stained with hematoxylin-eosin. The slides were screened for potential signs of adverse effects such as inflammation, intracellular lipid, protein, glycogen or pigment accumulation, degeneration, fibrosis or necrosis. RESULTS: In liver specimens from RvE1 group, intact hepatic microarchitecture was observed with no evidence of degeneration, necrosis, inflammation, or fibrosis. Kidney glomeruli, tubuli, intersticium, and blood vessels were normal with no signs of renal failure or fibrosis. Lung specimens were free of disorganization of the alveolar parenchyma with no proteinaceous debris or desquamation in alveolar bronchioles. In spleen, the white and red pulps of the parenchyma were normal. Myocytes were abundant; inflammatory cells and collagen were scarce thus representing an essentially normal myocardium in heart of RvE1-treated animals. CONCLUSION: Topical RvE1 application in the treatment of experimental periodontitis does not cause systemic toxicity on internal organs. Supported by USPHS Grant DE16191.