Evaluation of the Local Synergistic Effect of a Dexketoprofen and Chlorhexidine Combination in the Formalin Test.

OBJECTIVE: Evidence supports the local application of non-steroidal antiinflammatory drugs such as dexketoprofen trometamol (DXT) for pain management, but little is known about the potential antinociceptive effect of chlorhexidine gluconate (CHX) and its possible synergistic effect when combined with DXT. The aim of this study was to evaluate the local effect of a DXT-CHX combination using isobolographic analysis in a formalin pain model in rats. MATERIALS AND METHODS: Briefly, 60 female Wistar rats were used for the formalin test. Individual dose effect curves were obtained using linear regression. For each drug, the percentage of antinociception and median effective dose (ED50; 50% of antinociception) were calculated, and drug combinations were prepared using the ED50s for DXT (phase 2) and CHX (phase 1). The ED50 of the DXT-CHX combination was determined, and an isobolographic analysis was performed for both phases. RESULTS: The ED50 of local DXT was 5.3867 mg/mL in phase 2 and for CHX was 3.9233 mg/mL in phase 1. When the combination was evaluated, phase 1 showed an interaction index (II) of less than 1, indicating synergism but without statistical significance. For phase 2, the II was 0.3112, with a reduction of 68.88% in the amounts of both drugs to obtain the ED50; this interaction was statistically significant (P < .05). CONCLUSION: DXT and CHX had a local antinociceptive effect and exhibited synergistic behavior when combined in phase 2 of the formalin model.

Antinociceptive local effect of the combination of dexketoprofen trometamol and chlorhexidine gluconate in a formalin test: an additive effect

ABSTRACT A drug delivery system (DDS) with analgesic and antibacterial properties would be desirable for the local control of post-operatory pain and the prevention for surgical site infection (SSI). The objective of the present study was to evaluate the antinociceptive effect of the combination between dexketoprofen trometamol (DXT) and chlorhexidine gluconate (CHX) in the formalin pain model. Different doses of CHX were combined with DXT and were locally administered in rats paw simultaneously with 5% formalin dilution. Flinches were documented and the antinociceptive effect was calculated. The area under the curve of each experimental group were calculated and the % of antinociception were compared. The groups of CHX and DXT showed similar antinociceptive effect. The combination groups (DXT-CHX) showed higher antinociceptive effect that the one obtained with individual molecules. Besides the confirmation of DXT local antinociceptive properties, CHX also showed a positive effect; and an additive effect when combined with DXT

Effect of 4-Allyl-1-hydroxy-2-methoxybenzene (Eugenol) on Inflammatory and Apoptosis Processes in Dental Pulp Fibroblasts.

Eugenol (mixed with zinc oxide powder) is widely used as direct capping material during pulp therapy in primary teeth. The aim of the present study was to evaluate the effect of eugenol on diverse genes involved in inflammatory and cell apoptosis processes. The regulatory effect of eugenol on the expression of inflammation and apoptotic genes was evaluated in dental pulp fibroblasts from extracted third molars, cultured under concentration of eugenol of 13 µM. Eugenol allowed the expression of inflammatory and apoptotic genes when compared with positive and negative controls. Eugenol is a proinflammatory agent when it is in direct contact with healthy tissues and behaves as an anti-inflammatory agent in tissues undergoing inflammatory/apoptotic processes, as in cases of pulp inflammation in primary teeth. These findings are relevant for dentistry, when considering the application of safer pulp treatments to grossly carious children's teeth.

L-arginine reverses alterations in drug disposition induced by spinal cord injury by increasing hepatic blood flow.

High hepatic extraction drugs--such as phenacetin, methylprednisolone, and cyclosporine--exhibit an increased bioavailability after acute spinal cord injury (SCI) due to an impaired clearance. For these drugs, metabolic clearance depends on hepatic blood flow. Thus, it is possible that pharmacokinetic alterations can be reversed by increasing liver perfusion. Therefore, we evaluated the effect of L-arginine, a nitric oxide precursor, on the pharmacokinetics of a prototype drug with high hepatic extraction, and on hepatic microvascular blood flow (MVBF) after acute SCI. Pharmacokinetics of i.v. phenacetin was studied in rats 24 h after a severe T-5 spinal cord contusion; animals being pretreated with L-arginine 100 mg/kg i.v. or vehicle. MVBF was assessed under similar experimental conditions using laser Doppler flowmetry. SCI significantly altered phenacetin pharmacokinetics. Clearance was significantly reduced, resulting in a prolonged half-life and an increase in bioavailability, while volume of distribution was decreased. Pharmacokinetic alterations were reversed when injured rats were pretreated with L -arginine. It was also observed that L-arginine significantly increased hepatic MVBF in injured rats, notwithstanding it exhibited a limited effect on sham-injured animals. Our data hence suggest that L-arginine is able to reverse SCI-induced alterations in phenacetin pharmacokinetics due to an impaired hepatic MVBF, likely by increased nitric oxide synthesis leading to vasodilation. Further studies are warranted to examine the potential usefulness of nitric oxide supplementation in a clinical setting.