Periodontitis in rats induces systemic oxidative stress that is controlled by bone-targeted antiresorptives.
Periodontitis in rats induces systemic oxidative stress that is controlled by bone-targeted antiresorptives.
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DOI：
10.1902/jop.2014.140302
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发表时间：
2015-01
影响因子：
4.3
通讯作者：
Kesavalu L
中科院分区：
文献类型：
--
作者：
Oktay S;Chukkapalli SS;Rivera-Kweh MF;Velsko IM;Holliday LS;Kesavalu L
牙周炎是一种慢性、多种微生物的炎症性疾病，可降解结缔组织和牙槽骨，导致牙齿脱落。氧化应激与牙周组织破坏和全身性炎症的发生有关，抗吸收治疗的成功将取决于它们如何有效地改善口腔感染期间牙周疾病诱导的氧化应激。用由牙龈卟啉单胞菌、齿垢密螺旋体和嗜酸坦纳氏菌组成的多菌接种物感染大鼠，作为每隔一周的口腔灌洗，持续12周。在大鼠多细菌感染6周后，每天皮下注射依诺沙星、双依诺沙星、阿仑膦酸盐或强力霉素，持续6周。在每只感染、治疗和假感染大鼠中评价氧化应激参数和抗氧化酶（包括谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶）的血清水平。与对照组相比，牙周病原体感染的大鼠的氧化应激指数增加了5倍，这是由于血清氧化剂水平升高和总抗氧化活性降低。尽管三种重要的抗氧化酶增加，但抗氧化活性总体下降，这表明抗氧化大分子/小分子生产和抗氧化酶水平之间存在不平衡。令人惊讶的是，骨靶向抗吸收药双依诺沙星和阿仑膦酸盐抑制牙周炎引起的氧化应激增加。双依诺沙星具有抗骨吸收和抗生素活性，比阿仑膦酸钠更有效，阿仑膦酸钠仅作为抗骨吸收剂。据作者所知，这是第一项证明大鼠牙周感染引起的氧化应激增加可以通过骨靶向抗吸收药改善的研究。
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. 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. 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. 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.