Effect of an encapsulated anti-elastase compound on experimental gingival inflammation in the rat.
An animal (rat) model of gingival injury ("impaction") induced a gingival inflammatory reaction, which was characterized by a breakdown of gingival collagen and the elastic network, as well as a significant increase of gingival elastase. The present study was conducted to investigate whether ceramides, sphingolipids composed of sphingosine N-acyl-linked to fatty acids, a chemical structure with antielastase properties, could counteract the development of such an inflammatory process. The ceramides used in these experimental series were extracted from wheat and characterized. The main fatty acids were 16:0, 18:1, 18:2, and the sphingoid moiety was phytosphingosine. Inhibition of elastase by ceramides was demonstrated in vitro and the concentration necessary to inhibit 50% of elastase activity was 41 mg/l using the synthetic substrate methoxysuccinyl-alanine-alanine-proline-valine-p-nitroanilide (MeOSuc-AlaAlaProValpNA). However, this anti-elastase activity was not observed in vivo in our animal model of gingival inflammation. A glycosaminoglycan (Heparin), recognized as a potent inhibitor of elastase, was entrapped in ceramides. A local treatment of impacted gingivae by encapsulated heparin led to a dose-related decrease of the elastase level in gingival extracts. Encapsulation in ceramides potentiated the effect exerted by heparin alone. This inhibitory effect of encapsulated heparin on elastase suggested a vector effect of these amphipathic molecules.
Guessous
F
F
Département de Pharmacologie, CNRS URA 1534, Hôpital Cochin, Paris, France.
el Abbouyi
A
A
Giroud
J P
JP
Meyer
J
J
Roch-Arveiller
M
M
D000818:Animals; D002214:Capsules; D002518:Ceramides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005891:Gingivitis / Q000188:drug therapy* / Q000201:enzymology; D006493:Heparin / Q000494:pharmacology; D008297:Male; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014908:Triticum / Q000737:chemistry
D002214:Capsules; D002518:Ceramides; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D006493:Heparin; D010196:Pancreatic Elastase