Periodontitis in Rats Induces Systemic Oxidative Stress That Is Controlled by Bone‐Targeted Antiresorptives

Abstract

Background Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease–induced oxidative stress during oral infection. Methods Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bisenoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham-infected rats. Results Rats infected with the periodontal pathogens displayed a five-fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone-targeted antiresorptives bis-enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis-enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive. Conclusion To the best of the authors’ knowledge, this is the first study to demonstrate that the increased oxidative stress induced by periodontal infection in rats can be ameliorated by bone-targeted antiresorptives.

Quercetin and alendronate multi‐functionalized materials as tools to hinder oxidative stress damage

“…At variance, the beneficial effect of alendronate is rather unexpected, when considering that the adverse effects on gastrointestinal system of the oral administration of alendronate have been suggested to be related to oxidative damage . On the other hand, a recent study demonstrates that alendronate can reduce the oxidative stress induced by periodontal infection in rats . Moreover, inhibition of osteoclastogenesis induced in female mice by systemic administration of alendronate has been suggested to provoke a decrease of ROS generation .…”

Association of Serum Triglyceride Level and Gemfibrozil Consumption With Periodontal Status

“…A role has been proposed for oxidative stress in the pathogenesis of periodontal diseases 1 , 5 . By creating reactive oxygen species in the process of neutrophil activity, ionic balance is disrupted and periodontal tissue is damaged by production of free oxygen radicals such as OH and H 2 O 2 , leading to development of periodontal disease 12 , 32 . Factors capable of eliminating these free radicals or inhibiting their production can prevent the development or progression of periodontal disease 33–37 .…”

Periodontal Health and Disease in Glutathione Peroxidase

“…The plurality of periodontal tissue devastation is brought about by an unsuitable host response to those pathogens and their products (lipopolysaccharides and proteases) [11]. The coaction between pathogenic bacteria and the host's immune response is participated by chemokines, the produce of pro-inflammatory cytokines, and an exaggerated immune response, entailing an increase in the number and activity of polymorphonuclear leukocytes (PMNs) [12]. PMNs are the main mediators of host response averse to the bacteria [13].…”