Effects of cyclooxygenase inhibitors on nitric oxide production and survival in a mice model of sepsis


Tunctan B., Altug S., Uludag O. , Demirkay B., Abacioglu N.

PHARMACOLOGICAL RESEARCH, cilt.48, sa.1, ss.37-48, 2003 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 48 Konu: 1
  • Basım Tarihi: 2003
  • Doi Numarası: 10.1016/s1043-6618(03)00064-1
  • Dergi Adı: PHARMACOLOGICAL RESEARCH
  • Sayfa Sayıları: ss.37-48

Özet

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 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(1alpha) levels in all tissues. The decreased levels of nitrite induced by endotoxin is further reduced by 0.1 mg kg(-1) DFU and I and 10 mg kg(-1) diclophenac while 10 mg kg(-1) DFU and I mg kg(-1) proquazon increased it. On the other hand, I mg kg(-1) diclophenac and proquazon, and 10 mg 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. (C) 2003 Elsevier Science Ltd. All rights reserved.