Department of Stomatology, Discipline of Periodontology, School of Dentistry, University of São Paulo (FOUSP), São Paulo, São Paulo, Brazil.
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, São Paulo, Brazil.
J Periodontol. 2021 Aug;92(8):e84-e93. doi: 10.1002/JPER.20-0718. Epub 2021 Feb 19.
Leukotrienes (LTs) participate in the process of tissue damage in periodontal disease by leukocyte chemotaxis and osteoclastic activation. The activation of Cysteinyl-LT receptor is associated with increased expression of proinflammatory molecules and osteoclastogenesis. However, its implications on periodontal disease progression have not been studied. The present study evaluated the effect of the cysteinyl-LT receptor antagonist (montelukast [MT]) on ligature-induced experimental periodontitis (EP) in rats.
Adult male Wistar rats were subjected to bilateral ligature-induced periodontitis and orally treated with MT (at doses of 10 or 30 mg/kg/d, MT10, and MT30, respectively). Sham animals had the ligatures immediately removed and received placebo treatment. Sets of animals were euthanized 7, 14, or 21 days after ligature placement and the mandibles were removed for macroscopic evaluation of alveolar bone loss (ABL). In addition, histological analysis of periodontal tissues, myeloperoxidase (MPO) activity of gingival tissues, and periodontal tissue expression of collagen type I, RUNX2, RANK, RANKL, OPG, BLT1, Cys-LTR1, LTA4H, and LTC4S were also analyzed.
MT significantly reduced ABL at 14 (MT10 and MT30) and 21 days (MT10) (P < 0.05), gingival MPO at 7 (MT10) and 14 days (MT30) (P < 0.05), LTA4H, BLT1 and LTC4S gene expression on day 14 day (MT30, P < 0.05) and increased RUNX2 expression on day 14 (MT30, P < 0.05).
Systemic therapy with MT decreases periodontal inflammation and ABL in ligature-induced periodontitis in rats.
白三烯（LTs）通过白细胞趋化作用和破骨细胞激活参与牙周病组织损伤。半胱氨酰-LT 受体的激活与促炎分子的表达增加和破骨细胞生成有关。然而，其对牙周病进展的影响尚未研究。本研究评估了半胱氨酰-LT 受体拮抗剂（孟鲁司特[MT]）对大鼠结扎诱导牙周炎（EP）的影响。
成年雄性 Wistar 大鼠双侧结扎诱导牙周炎，给予 MT 口服治疗（剂量分别为 10 或 30mg/kg/d，MT10 和 MT30）。假手术动物立即去除结扎线并给予安慰剂治疗。结扎后 7、14 或 21 天处死一组动物，取出下颌骨进行牙槽骨丧失（ABL）的大体评估。此外，还分析了牙周组织的组织学分析、牙龈组织的髓过氧化物酶（MPO）活性以及牙周组织中胶原 I、RUNX2、RANK、RANKL、OPG、BLT1、Cys-LTR1、LTA4H 和 LTC4S 的表达。
MT 显著降低了 14 天（MT10 和 MT30）和 21 天（MT10）的 ABL（P<0.05）、7 天（MT10）和 14 天（MT30）的牙龈 MPO（P<0.05）、14 天的 LTA4H、BLT1 和 LTC4S 基因表达（MT30，P<0.05）和 14 天的 RUNX2 表达（MT30，P<0.05）。
MT 全身治疗可减少大鼠结扎诱导牙周炎中的牙周炎症和 ABL。
