ABSTRACT
BACKGROUND: Arachidonate-5-lipoxygenase (5-LO) activity and increased leukotriene B4 (LTB4) production have been implicated in various inflammatory conditions. Increased production of leukotrienes has been associated with periodontal diseases; however their relative contribution to the tissue destruction is unknown. We used an orally-active specific 5-LO inhibitor to assess its role in inflammation and bone resorption in a murine model of lipopolysaccharide (LPS)-induced periodontal disease. METHODS: Periodontal disease was induced in Balb/c mice by direct injections of LPS into the palatal gingival tissues adjacent to the upper first molars 3 times/week for four weeks. Animals were treated with the biochemical inhibitor (2 mg/Kg/day) or the same volume of the vehicle by oral gavage. µCT analysis was used to assess bone resorption. EIA determined leukotriene B4, and ELISAs quantified TNF, IL-12 and IL-10 in the gingival tissues. Histological sections were used for the morphometric analysis (number neutrophils and mononuclear cells). Osteoclasts were counted in TRAP-stained sections. RESULTS: Administration of 5-LO inhibitor effectively reduced the production of LTB4 (23.7% decrease) and significantly reduced TNF and IL-12 levels in the gingival tissues. Moreover, reduction of LTB4 levels in the gingival tissues was associated with a significant decrease in bone resorption and a marked reduction in the number of osteoclasts and inflammatory cells. CONCLUSION: 5-LO activity plays a relevant role in inflammation and bone resorption associated with the LPS model of experimental periodontal disease.
ABSTRACT
Three new isoaigialones, A, B, and C (1-3), along with aigialone (4), were isolated from the crude EtOAc extract of a Phaeoacremonium sp., an endophytic fungus obtained from the leaves of Senna spectabilis. The structures of these compounds were elucidated based on the analysis of spectroscopic data. Compounds 2 and 4 were active against the phytopathogenic fungi Cladosporium cladosporioides and C. sphaerospermum. This is the first report of metabolites produced by an Phaeoacremonium sp., associated with S. spectabilis.
Subject(s)
Acetals/isolation & purification , Acetals/pharmacology , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Ascomycota/chemistry , Cladosporium/chemistry , Ketones/isolation & purification , Ketones/pharmacology , Lactones/isolation & purification , Plant Leaves/chemistry , Senna Plant/chemistry , Acetals/chemistry , Antifungal Agents/chemistry , Ketones/chemistry , Lactones/chemistry , Lactones/metabolism , Lactones/pharmacology , Molecular StructureABSTRACT
BACKGROUND: Arachidonate-5-lipoxygenase (5-LO) activity and increased leukotriene B4 (LTB4) production have been implicated in various inflammatory conditions. Increased production of leukotrienes has been associated with periodontal diseases; however, their relative contribution to tissue destruction is unknown. In this study, an orally active specific 5-LO inhibitor is used to assess its role in inflammation and bone resorption in a murine model of lipopolysaccharide (LPS)-induced periodontal disease. METHODS: Periodontal disease was induced in Balb/c mice by direct injections of LPS into the palatal gingival tissues adjacent to the maxillary first molars three times per week for 4 weeks. Animals were treated with biochemical inhibitor (2 mg/kg/daily) or the same volume of the vehicle by oral gavage. Microcomputed tomography analysis was used to assess bone resorption. Enzyme immunoassay determined LTB4, and enzyme-linked immunosorbent assays quantified tumor necrosis factor (TNF), interleukin (IL)-12, and IL-10 in gingival tissues. Histologic sections were used for the morphometric analysis (number of neutrophils and mononuclear cells). Osteoclasts were counted in tartrate-resistant acid phosphatase-stained sections. RESULTS: Administration of 5-LO inhibitor effectively reduced production of LTB4 (23.7% decrease) and significantly reduced TNF and IL-12 levels in gingival tissues. Moreover, reduction of LTB4 levels in gingival tissues was associated with a significant decrease in bone resorption and a marked reduction in number of osteoclasts and inflammatory cells. CONCLUSION: 5-LO activity plays a relevant role in inflammation and bone resorption associated with the LPS model of experimental periodontal disease.
