Experimental basis for the efficacy of mitochondria-targeted agents for periodontal diseases: a laboratory study

BACKGROUND: Recent evidence indicates a role of mitochondrial dysfunction in the etiopathogenesis of periodontitis. As active participants in cellular metabolic and energy processes, mitochondria constitute key components of oxidative stress pathways. AIM: The study aimed to evaluate the potential use of mitochondria-targeted agents as part of comprehensive therapy for inflammatory periodontal diseases. METHODS: An experimental study of the effect of the mitochondria-targeted agent 5-aminoimidazole-4-carboxamide riboside on periodontitis was conducted. Male Wistar rats (Rattus Wistar) aged 4 months with a body weight of 221.0 ± 7.5 g were used in the study. Five experimental groups were formed: a control group (healthy animals); animals with experimentally induced periodontitis; main group I, in which periodontitis was treated with topical application of a gel containing metronidazole and chlorhexidine for 7 days; main group II, in which periodontitis was treated with topical application of the metronidazole-chlorhexidine gel combined with simultaneous oral administration of 5-aminoimidazole-4-carboxamide riboside also for 7 days; main group III, in which periodontitis was treated with topical application of the metronidazole- chlorhexidine gel followed by topical administration of 5-aminoimidazole-4-carboxamide riboside, also for 7 days. Mitochondrial alterations in periodontal tissues were investigated using molecular genetic analysis of characteristics of nuclear and mitochondrial DNA (mtDNA), as well as biochemical assessment of oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione. RESULTS: Mitochondrial alterations characteristic of experimental periodontitis were largely reversed following treatment with a metronidazole–chlorhexidine gel, with up to 80% normalization based on mtDNA amplification metrics and mutation frequency (up to 7%). The addition of a mitochondria-targeted agent resulted in a more pronounced improvement, reaching 97% normalization in mtDNA quantity and reducing mutation frequency to 2%. Oxidative stress associated with periodontitis decreased after treatment with the metronidazole–chlorhexidine gel, as reflected by an 18% reduction in MDA concentration and a 32% increase in glutathione concentration. With combined therapy including the mitochondria-targeted agent administered after gel treatment (main group III), а 57% reduction in MDA concentration and a 49% increase in glutathione concentration were recorded. CONCLUSION: This study demonstrates improvement in mitochondrial parameters in periodontal tissues following completion of therapy for experimental periodontitis using a metronidazole-chlorhexidine gel and its combination with a mitochondria-targeted agent. Incorporation of 5-aminoimidazole-4-carboxamide riboside into the treatment regimen produced a more pronounced therapeutic effect, as evidenced by the parameters of mtDNA amplification quantity and mutant copies frequency and by markers of oxidative stress.