ABSTRACT
Nuclear factor-kappaB (NF-kappaB) is a transcription factor which plays a pivotal role in the induction of genes involved in physiological processes as well as in the response to injury and inflammation. Dithiocarbamates are antioxidants which are potent inhibitors of NF-kappaB. We postulated that pyrrolidine dithiocarbamate (PDTC) would attenuate inflammation. In the present study, we have investigated the effects of PDTC, in a rat model of periodontitis. Periodontitis was induced in rats by placing around the lower left first molar a 2/0 braided silk. At day eight the gingivomucosal tissue encircling the mandibular first molar was removed for biochemical and histological analysis. At day eight ligations significantly induced an increase neutrophil infiltration as well as the gingivomucosal tissue expression of TNF-alpha and iNOS as well as nitrotyrosine formation and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitonial injection of PDTC (10 mg/kg daily for eight days) significantly reduced all of the parameters of inflammation as described above. These data demonstrate that PDTC exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage associated with ligature-induced periodontitis.
Subject(s)
Periodontitis/drug therapy , Pyrrolidines/therapeutic use , Thiocarbamates/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Male , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , Periodontitis/enzymology , Periodontitis/metabolism , Periodontitis/pathology , Pyrrolidines/pharmacology , Rats , Rats, Sprague-Dawley , Thiocarbamates/pharmacologyABSTRACT
Recent studies have demonstrated that cloricromene, a coumarin derivative, exerts protective effects in models of inflammation and shock. Tumour necrosis factor plays a pivotal role in the induction of genes involved in physiological processes, as well as in the response to inflammation. We investigated the effect of cloricromene in a rat model of periodontitis. Periodontitis was induced in rats by placing a 2/0 braided silk ligature around the lower left first molar. At day 8 the gingivomucosal tissue encircling the mandibular first molar was removed for evaluation of tumour necrosis factor production, neutrophil infiltration, tissue permeability, nitrotyrosine formation, poly (ADP-ribose) polymerase activation, radiography and histology. Ligation significantly induced an increased tumour necrosis factor production, neutrophil infiltration and a positive staining for nitrotyrosine formation and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone erosion as evaluated by radiography analysis. Intraperitonal injection of cloricromene (10 mg/kg daily for 8 days) significantly decreased all of the parameters of inflammation as described above. This suggests that cloricromene treatment, which reduced tumour necrosis factor production, may be of benefit in the treatment of periodontitis.
Subject(s)
Chromonar/analogs & derivatives , Periodontitis/prevention & control , Animals , Capillary Permeability/drug effects , Chromonar/pharmacology , Chromonar/therapeutic use , Male , Neutrophil Infiltration , Periodontitis/metabolism , Periodontitis/pathology , Poly(ADP-ribose) Polymerases/metabolism , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesis , Tyrosine/analogs & derivatives , Tyrosine/biosynthesisABSTRACT
BACKGROUND: Recent studies have demonstrated that Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a cell membrane-permeable radical scavenger, exerts protective effects in various models of inflammation and shock. Reactive oxygen species (ROS) plays a pivotal role in the induction of genes involved in physiological processes as well as in the response to inflammation. AIM: We have investigated the effect of Tempol in a rat model of periodontitis. MATERIALS AND METHODS: Periodontitis was induced in rats by placing a 2/0 braided silk ligature around the lower left first molar. At day 8, the gingivomucosal tissue encircling the mandibular first molar was removed for evaluation of neutrophils infiltration, tissue permeability, nitrotyrosine formation, poly-(ADP-ribose) polymerase (PARP) activation, radiography and histology. RESULTS AND CONCLUSIONS: Legation significantly induced an increased neutrophil infiltration and a positive staining for nitrotyrosine formation and PARP activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone erosion as evaluated by radiography analysis. Intraperitonial injection of Tempol (10 mg/kg daily for 8 days) significantly decreased all of the parameters of inflammation as described above. This suggests that antioxidant therapies, which interfere with ROS, may be of benefit in the treatment of periodontitis.
