Skip to main content
PMC home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1992;1(5):335–339. doi: 10.1155/S0962935192000504

Leukotriene inhibition in hamster periodontitis. A histochemical and morphometric study

B Baroukh 1, J L Saffar 1,✉
PMCID: PMC2365357  PMID: 18475481

Abstract

The effects of leukotriene (LT) inhibition on gingival and adjacent bone compartments were assessed by using phenidone (100 mg/kg/d) and ketoconazole (50 mg/kg/d) given for 4 weeks to periodontitis-affected hamsters. In the gingiva the two agents significantly decreased PMNL recruitment and migration and increased the vascular lumen. At the bone level, they reduced significantly preosteoclast and osteoclast numbers but did not affect osteoclast activity. Phenidone had no action on periodontitis induced inhibition of bone formation; in contrast ketoconazole enhanced formation. As both phenidone and ketoconazole are unspecific LT inhibitors it cannot be ascertained that the effects observed were actually due to LT inhibition. However, phenidone and ketoconazole induced changes different from indomethacin used in previous studies to inhibit the cyclooxygenase pathway. These discrepancies suggest that LT inhibition occurred in the present study and that they participate in gingival inflammation and osteoclastic destruction during hamster periodontitis.

Full Text

The Full Text of this article is available as a PDF (536.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baroukh B., Saffar J. L. Identification of osteoclasts and their mononuclear precursors. A comparative histological and histochemical study in hamster periodontitis. J Periodontal Res. 1991 May;26(3 Pt 1):161–166. doi: 10.1111/j.1600-0765.1991.tb01640.x. [DOI] [PubMed] [Google Scholar]
  2. Beetens J. R., Loots W., Somers Y., Coene M. C., De Clerck F. Ketoconazole inhibits the biosynthesis of leukotrienes in vitro and in vivo. Biochem Pharmacol. 1986 Mar 15;35(6):883–891. doi: 10.1016/0006-2952(86)90072-9. [DOI] [PubMed] [Google Scholar]
  3. Blackwell G. J., Flower R. J. 1-phenyl-3-pyrazolidone: an inhibitor of cyclo-oxygenase and lipoxygenase pathways in lung and platelets. Prostaglandins. 1978 Sep;16(3):417–425. doi: 10.1016/0090-6980(78)90220-4. [DOI] [PubMed] [Google Scholar]
  4. Carlson R. P., O'Neill-Davis L., Chang J., Lewis A. J. Modulation of mouse ear edema by cyclooxygenase and lipoxygenase inhibitors and other pharmacologic agents. Agents Actions. 1985 Dec;17(2):197–204. doi: 10.1007/BF01966592. [DOI] [PubMed] [Google Scholar]
  5. Carter-Bartlett P., Dersot J. M., Saffar J. L. Periodontal and femoral bone status in periodontitis-affected hamsters receiving a high dose indomethacin treatment. J Biol Buccale. 1989 Jun;17(2):93–101. [PubMed] [Google Scholar]
  6. Dahlén S. E., Björk J., Hedqvist P., Arfors K. E., Hammarström S., Lindgren J. A., Samuelsson B. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3887–3891. doi: 10.1073/pnas.78.6.3887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davies P., Bailey P. J., Goldenberg M. M., Ford-Hutchinson A. W. The role of arachidonic acid oxygenation products in pain and inflammation. Annu Rev Immunol. 1984;2:335–357. doi: 10.1146/annurev.iy.02.040184.002003. [DOI] [PubMed] [Google Scholar]
  8. Dunham B. M., Hechtman H. B., Valeri C. R., Shepro D. Antiinflammatory agents inhibit microvascular permeability induced by leukotrienes and by stimulated human neutrophils. Microcirc Endothelium Lymphatics. 1984 Aug;1(4):465–489. [PubMed] [Google Scholar]
  9. Fels A. O., Pawlowski N. A., Cramer E. B., King T. K., Cohn Z. A., Scott W. A. Human alveolar macrophages produce leukotriene B4. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7866–7870. doi: 10.1073/pnas.79.24.7866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  11. Makris G. P., Saffar J. L. Disturbances in bone remodeling during the progress of hamster periodontitis. A morphological and quantitative study. J Periodontal Res. 1985 Jul;20(4):411–420. doi: 10.1111/j.1600-0765.1985.tb00453.x. [DOI] [PubMed] [Google Scholar]
  12. McMillan R. M., Foster S. J. Leukotriene B4 and inflammatory disease. Agents Actions. 1988 Jun;24(1-2):114–119. doi: 10.1007/BF01968088. [DOI] [PubMed] [Google Scholar]
  13. Meghji S., Sandy J. R., Scutt A. M., Harvey W., Harris M. Stimulation of bone resorption by lipoxygenase metabolites of arachidonic acid. Prostaglandins. 1988 Aug;36(2):139–149. doi: 10.1016/0090-6980(88)90301-2. [DOI] [PubMed] [Google Scholar]
  14. Moser R., Schleiffenbaum B., Groscurth P., Fehr J. Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest. 1989 Feb;83(2):444–455. doi: 10.1172/JCI113903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nolan K. D., Keagy B. A., Ramadan F. M., Johnson G., Jr, Henke D. C. Endothelial cells can synthesize leukotriene B4. J Vasc Surg. 1990 Sep;12(3):298–304. [PubMed] [Google Scholar]
  16. Palder S. B., Huval W., Lelcuk S., Alexander F., Shepro D., Mannick J. A., Hechtman H. B. Reduction of polymorphonuclear leukocyte accumulations by inhibition of cyclooxygenase and thromboxane syntase in the rabbit. Surgery. 1986 Jan;99(1):72–81. [PubMed] [Google Scholar]
  17. Reinhardt T. A., Horst R. L. Ketoconazole inhibits self-induced metabolism of 1,25-dihydroxyvitamin D3 and amplifies 1,25-dihydroxyvitamin D3 receptor up-regulation in rat osteosarcoma cells. Arch Biochem Biophys. 1989 Aug 1;272(2):459–465. doi: 10.1016/0003-9861(89)90240-3. [DOI] [PubMed] [Google Scholar]
  18. Saffar J. L., Leroux P. Role of prostaglandins in bone resorption in a synchronized remodeling sequence in the rat. Bone. 1988;9(3):141–145. doi: 10.1016/8756-3282(88)90003-8. [DOI] [PubMed] [Google Scholar]
  19. Sandy J. R., Meikle M. C., Martin B. R., Farndale R. W. Leukotriene B4 increases intracellular calcium concentration and phosphoinositide metabolism in mouse osteoblasts via cyclic adenosine 3',5'-monophosphate-independent pathways. Endocrinology. 1991 Aug;129(2):582–590. doi: 10.1210/endo-129-2-582. [DOI] [PubMed] [Google Scholar]
  20. Snyder D. W., Fleisch J. H. Leukotriene receptor antagonists as potential therapeutic agents. Annu Rev Pharmacol Toxicol. 1989;29:123–143. doi: 10.1146/annurev.pa.29.040189.001011. [DOI] [PubMed] [Google Scholar]
  21. Tatsuno I., Saito H., Chang K. J., Tamura Y., Yoshida S. Comparison of the effect between leukotriene B4 and leukotriene B5 on the induction of interleukin 1-like activity and calcium mobilizing activity in human blood monocytes. Agents Actions. 1990 Mar;29(3-4):324–327. doi: 10.1007/BF01966464. [DOI] [PubMed] [Google Scholar]
  22. Ward P. A., Marks R. M. The acute inflammatory reaction. Curr Opin Immunol. 1989 Oct;2(1):5–9. doi: 10.1016/0952-7915(89)90090-3. [DOI] [PubMed] [Google Scholar]
  23. elAttar T. M., Lin H. S., Killoy W. J., Vanderhoek J. Y., Goodson J. M. Hydroxy fatty acids and prostaglandin formation in diseased human periodontal pocket tissue. J Periodontal Res. 1986 Mar;21(2):169–176. doi: 10.1111/j.1600-0765.1986.tb01449.x. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES