Abstract
The effects of selective ((5,5-dimethyl-3-(3-florophenyl)-4-(4-methylsulphonyl-2(5 H)-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 1α (6-keto-PGF 1α, 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 kg −1, i.p.)-induced mortality was prevented by DFU, NS 398 and proquazon (0.1, 10 and 1 mg kg −1, respectively) and enhanced 2.6-fold with 0.1 mg kg −1 diclophenac. Endotoxin-induced increase in the serum levels of nitrite was only inhibited by 10 mg kg −1 diclophenac. Endotoxin caused a significant decrease only in the brain levels of nitrite without affecting 6-keto-PGF 1α levels in all tissues. The decreased levels of nitrite induced by endotoxin is further reduced by 0.1 mg kg −1 DFU and 1 and 10 mg kg −1 diclophenac while 10 mg kg −1 DFU and 1 mg kg −1 proquazon increased it. On the other hand, 1 mg kg −1 diclophenac and proquazon, and 10 mg kg −1 NS 398 increased the endotoxin-induced lung levels of 6-keto-PGF 1α. The results suggest that the COX inhibitors may have different effects on the survival and NO production depending on tissue and dose.
Published Version
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