This study was designed to investigate the effect of TTHL on nociception and vascular permeability induced by acetic acid. We also evaluated the effect of TTHL on carrageenan-induced peritonitis and the levels of cytokines (interleukin 1-尾 [IL-1尾], tumor necrosis factor 伪 [TNF-伪] and interleukin 10 [IL-10]) on peritoneal fluid.
TTHL was administered orally by intra-gastric gavage (i.g.) 60 min prior to experimentation. Abdominal contractions and vascular permeability were induced by an intraperitoneal (i.p.) injection of acetic acid (0.6%). We also investigated whether TTHL decreases carrageenan-induced peritonitis (750 渭g/cavity) by measuring leukocyte migration and vascular permeability. In addition, we evaluated the effects of TTHL on TNF-伪, IL-1尾 and IL-10 release induced by carrageenan on peritoneal fluid. The levels of these cytokines were measured by ELISA.
TTHL (0.01-10 mg/kg) administered by intra-gastric (i.g.) gavage inhibited (69卤3%) acetic acid-induced abdominal constrictions, with an ID50 of 0.15 (0.03-0.8) mg/kg. TTHL (10 mg/kg) also reduced the leukocyte infiltration induced by acetic acid, with an inhibition of 59卤9 but had no effect on abdominal vascular permeability. In addition, indomethacin (10 mg/kg, i.p.) reduced the nociceptive behavior (92卤1%), total leukocyte migration (29卤3%) and capillary permeability (71卤3%) induced by acetic acid. While the glucocorticoid dexamethasone (2 mg/kg, s.c.) reduced partially but significantly the nociception (31卤1%), besides to promote a marked reduction on total leukocyte migration (60卤2%) to the peritoneal cavity caused by acetic acid. In a model of peritonitis induced by carrageenan, TTHL also reduced total leukocyte migration, mainly neutrophils (inhibition of 84卤3%and 85卤2%at 30 mg/kg and 100 mg/kg, respectively). Likewise, dexamethasone (0.5 mg/kg, i.p.) resulted in an inhibition of 93卤3%. Nevertheless, carrageenan-induced abdominal vascular permeability was reduced by dexamethasone but was not altered by TTHL. Furthermore, dexamethasone and TTHL significantly reduced the TNF-伪 and IL-1尾 levels in peritoneal fluid, whereas the IL-10 levels were unchanged.
Altogether, our data confirm the antinociceptive effect of TTHL and demonstrate its effect in inflammatory animal models, providing novel data about this compound, which could be useful as an anti-inflammatory drug.