6-ketoprostaglandin-f1-alpha and proquazone

The effects of selective ((5,5-dimethyl-3-(3-florophenyl)-4-(4-methylsulphonyl-2(5H)-furanon); DFU) and (N-(2-cyclohexyloxy-4-nitrophenyl)-methansulphonamide; NS 398)) or non-selective (diclophenac and proquazon) inducible cyclooxygenase (COX-2) inhibitors on the survival, nitrite (stable product of nitric oxide (NO) as an index for inducible NO synthase (iNOS) activity) and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha), stable product of prostacyclin as an index for COX-2 activity) production in serum, lungs, brain and/or kidney were investigated in endotoxin-induced sepsis model in mice. Endotoxin (10 mg x kg(-1), i.p.)-induced mortality was prevented by DFU, NS 398 and proquazon (0.1, 10 and 1 mg x kg(-1), respectively) and enhanced 2.6-fold with 0.1mg x kg(-1) diclophenac. Endotoxin-induced increase in the serum levels of nitrite was only inhibited by 10 mg x kg(-1) diclophenac. Endotoxin caused a significant decrease only in the brain levels of nitrite without affecting 6-keto-PGF(1alpha) levels in all tissues. The decreased levels of nitrite induced by endotoxin is further reduced by 0.1mg x kg(-1) DFU and 1 and 10mg x kg(-1) diclophenac while 10 mg x kg(-1) DFU and 1mg x kg(-1) proquazon increased it. On the other hand, 1mg x kg(-1) diclophenac and proquazon, and 10 mg x kg(-1) NS 398 increased the endotoxin-induced lung levels of 6-keto-PGF(1alpha). The results suggest that the COX inhibitors may have different effects on the survival and NO production depending on tissue and dose.

Topics: 6-Ketoprostaglandin F1 alpha; Analysis of Variance; Animals; Cyclooxygenase Inhibitors; Diclofenac; Disease Models, Animal; Female; Furans; Lipopolysaccharides; Male; Mice; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Quinazolines; Sepsis; Sulfonamides

The effects of one-day treatment with nine nonsteroidal anti-inflammatory drugs and prednisolone on human synovial fluid concentrations of prostanoids were studied. The doses were calculated so as to be approximately equipotent according to clinical experience and the recommendations of the manufacturers. Most of the drugs used reduced clearly PGE2 and TxB2 levels in synovial fluid, but only a slight diminution in 6-keto-PGF1 alpha values was found. Carprofen, diclofenac, indomethacin, naproxen and tolfenamic acid reduced significantly the synovial fluid PGE2 concentrations. Diclofenac and indomethacin also reduced significantly the synovial TxB2 concentrations.

Topics: 6-Ketoprostaglandin F1 alpha; Acetaminophen; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Carbazoles; Diclofenac; Dinoprostone; Guanidines; Humans; Indomethacin; Naproxen; ortho-Aminobenzoates; Prednisolone; Prostaglandins; Prostaglandins E; Quinazolines; Synovial Fluid; Thromboxane B2