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bioRxiv · 10.1101/2025.10.06.680686

Reversing Nicotine Toxicity: how Platelet-Rich Plasma Enhances Cell Recovery through Autophagy Modulation

Veriepe-Salerno, J.·Cancela, J.·Vischer, S.·Turzi, A.·Cuendet, M.·Giannopoulou, C.·Berndt, S.
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Abstract

BackgroundChronic exposure to nicotine significantly exacerbates periodontitis, a prevalent inflammatory disease, by inducing cellular processes such as autophagy and inflammation in gingival fibroblasts. Current therapies often fail to fully address these cellular alterations in smokers, highlighting a need for innovative therapeutic and generative approaches. ObjectiveThis study explores the therapeutic potential of Platelet-Rich Plasma (PRP), a blood-derived product, to modulate nicotine-induced biological activities in primary gingival fibroblasts. It aims at understanding the underlying cellular mechanisms and assessing the efficacy of PRP as an adjunct treatment for periodontitis in smokers. MethodsGingival fibroblasts were treated with increasing concentrations of nicotine, which led to senescence and autophagy. Subsequent treatment with autologous PRP was evaluated for its effect on the reversion of these processes, by measuring cell migration and proliferation, metabolic activity, as well as by looking at senescence and autophagic markers. A Caenorhabditis elegans model of autophagy was used to assess nicotine and PRP biological activities in an in vivo environment. ResultsNicotine at high concentrations triggered cellular vacuolization, a decrease in metabolism, viability and proliferation that was partially (with 500 ng/ml nicotine) or completely (with 250 ng/ml nicotine) reversed by a concomitant treatment with 10% PRP. Nicotine alone (250 ng/ml) slightly enhanced migration, while concomitant treatment between nicotine and PRP significantly increased their migration potential. In Caenorhabditis elegans, PRP reduced the nicotine-induced autophagic activity, as evidenced by decreased numbers of autophagosome and a higher number of viable worms during adulthood in comparison to nicotine control conditions. A screening of gingival fibroblast secretome revealed a modulation of autophagy-related cytokines in response to nicotine and/or PRP. ConclusionThe findings demonstrate that PRP could effectively inhibit nicotine-induced autophagy gingival fibroblasts, offering insights into its possible use as a therapeutic tool for managing periodontitis in smokers. The study underscores the potential of PRP in altering disease progression by modulating key cellular processes affected by smoking.

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Veriepe-Salerno, J., Cancela, J., Vischer, S., Turzi, A., Cuendet, M., Giannopoulou, C., Berndt, S.. 2025-10-07. Reversing Nicotine Toxicity: how Platelet-Rich Plasma Enhances Cell Recovery through Autophagy Modulation. https://doi.org/10.1101/2025.10.06.680686

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