Endotoxin tolerance in the periodontal of rats: participation of the nitric oxide

Author(s)

Valéria Pontelli Navarro Tedeschi

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Odontologia de Ribeirão Preto (PCARP/BC)
• Defense date: 2009-12-09

Examining board members

Luiz Guilherme de Siqueira Branco; Maria Camila Almeida; Kênia Cardoso Bícego; Teresa Lucia Colussi Lamano; Carlos Renato Tirapelli

• Advisor: Luiz Guilherme de Siqueira Branco

Abstract

Systemic injection of repeated doses of Escherichia coli lipopolysaccharide (LPS) results in attenuation of the febrile response, i.e. endotoxin tolerance, which has been well characterized systemically in rats. In the present study, we tested the hypothesis that endotoxin tolerance also occurs after repeated local injection of LPS into periodontal protection tissue of rats and that nitric oxide plays a role in this mechanism. Male Wistar rats were given a gingival injection of sterile saline or LPS at a dose of 100 μg/kg on three consecutive days with 24 hours break. Body core temperature (Tb) was measured with a miniature datalogger 1 hour before and 6 hours after the injections. Another group received L-NMMA (500 μg/rat) intracerebroventricular (i.c.v.), 30 minutes before LPS, in the third day. Besides it, was performed the Fos immunohistochemistry to verify the neuronal activation in the preoptic area of hypothalamus (POA) and in the subnucleus caudalis of spinal trigeminal nucleus in the first day (non-tolerant animals), in the third day of LPS treatment (tolerant animals) and in the animals that received L-NMMA or saline i.c.v. in the third day, before LPS. On day one we observed a polyphasic febrile response after LPS injection. On day two this response was sensitized and on day three the febrile response was completely abolished, characterizing the development of the endotoxin tolerance in the oral cavity. This tolerance was reverted with the pretreatment with L-NMMA in the third day and the animals develop the febrile response. The immunohistochemistry detected an increase in Fos protein expression in the subnucleus caudalis of spinal trigeminal nucleus and in the POA on day one in animals that received LPS and a reduction in Fos expression was observed on day three. Similarly to the reversion of the tolerance mechanism by the development of the febrile response in the third day, the pretreatment with L-NMMA, increased the number of Fos positive cells in both studied areas. These results indicate that rats develop endotoxin tolerance in periodontal tissues and that nitric oxide plays a role in this mechanism. (AU)