Equivalent intraperitoneal doses of ibuprofen supplemented in drinking water or in diet: a behavioral and biochemical assay using antinociceptive and thromboxane inhibitory dose-response curves in mice.

Background. Ibuprofen is used chronically in different animal models of inflammation by administration in drinking water or in diet due to its short half-life. Though this practice has been used for years, ibuprofen doses were never assayed against parenteral dose-response curves. This study aims at identifying the equivalent intraperitoneal (i.p.) doses of ibuprofen, when it is administered in drinking water or in diet. Methods. Bioassays were performed using formalin test and incisional pain model for antinociceptive efficacy and serum TXB2 for eicosanoid inhibitory activity. The dose-response curve of i.p. administered ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg body weight (b.w.). The dose-response curves were constructed of phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents), the area under the 'change in mechanical threshold'-time curve in the incisional pain model and serum TXB2 levels. The assayed ibuprofen concentrations administered in drinking water were 0.2, 0.35, 0.6 mg/ml and those administered in diet were 82, 263, 375 mg/kg diet. Results. The 3 concentrations applied in drinking water lay between 73.6 and 85.5 mg/kg b.w., i.p., in case of the formalin test; between 58.9 and 77.8 mg/kg b.w., i.p., in case of the incisional pain model; and between 71.8 and 125.8 mg/kg b.w., i.p., in case of serum TXB2 levels. The 3 concentrations administered in diet lay between 67.6 and 83.8 mg/kg b.w., i.p., in case of the formalin test; between 52.7 and 68.6 mg/kg b.w., i.p., in case of the incisional pain model; and between 63.6 and 92.5 mg/kg b.w., i.p., in case of serum TXB2 levels. Discussion. The increment in pharmacological effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those of i.p. administered ibuprofen. It is therefore difficult to assume the equivalent parenteral daily doses based on mathematical calculations.

Ibuprofen suppresses depressive like behavior induced by BCG inoculation in mice: role of nitric oxide and prostaglandin.

Prostaglandins (PGs) and nitric oxide (NO) may be involved in the pathophysiology of depression. Since NSAIDs decrease PGs and NO production, they may have an antidepressant effect. The aim of the present work was to explore a possible antidepressant action of ibuprofen in the new model of Bacillus Calmette-Guerin (BCG) induced depression. Mice injected with BCG (10(7) CFU/mouse intraperitoneally) showed an increase in the total immobility time during the forced swim test (FST) and the tail suspension test (TST) and an increase in cerebral PGE2 and NO levels. Fluoxetine administered in drinking water at a dose of 80 mg/l, 5 days before BCG and for 2 more weeks resulted in significant decrease in total immobility time during FST and TST and in cerebral PGE2 and NO levels. Both ibuprofen (200 mg/l) and L-NAME (1 g/l) administered in drinking water 24 h before BCG and for 2 more weeks resulted in decrease in the total immobility time during FST and TST and in cerebral PGE2 and NO levels, which was comparable to fluoxetine's effect. On the other hand, l-arginine administered at a dose of 6 g/l in drinking water together with ibuprofen or fluoxetine reversed their effect on FST, TST and cerebral PGE2 and NO levels. Immunohistochemistry showed a decrease in COX-1 and i-NOS immunoreactivity in the CA1 and CA3 areas of the hippocampus following ibuprofen treatment. These results suggest that ibuprofen may have an antidepressant effect through inhibition of PGE2 and NO production, especially in depression secondary to chronic inflammation.