Halis SÜLEYMAN, Hülya AKSOY, Berna DEMİRCAN, Yaşar Nuri ŞAHİN, Halise İnci GÜL

Karagenin ile oluşturulmuş pençe ödemi modelinde 3-benzoil-1-metil-4-fenil-4- piperidinol-hidroklorür (C1), indometazin, nimesulid ve rofekoksib’in siklooksijenaz enzim aktiviteleri üzerine olan etkileri

Amaç: Çalışmanın amacı 3-benzoil-1-metil-4-fenil-4-piperidinol-hidroklorür (C1) molekülünün karagenin ileoluşturulmuş pençe ödemi inflamasyonu modelinde siklooksijenaz (COX) enzim aktiviteleri üzerine etkilerini araştırmakve bu etkisini diğer nonsteroid antiinflamatuar ilaçlarla (NSAİİ) karşılaştırmaktı.Yöntem ve gereç: Deney hayvanları Atatürk Üniversitesi Deneysel Araştırma ve Uygulama Merkezinden sağlandı.Hayvanlar standart laboratuar koşullarında beslendi ve her grupta 6 rat olmak üzere 8 gruba ayrıldı. Bu gruplar; kontrol,intakt, indometazin, nimesulid, rofekoksib, C1 (50 mg) C1 (100 mg) ve C1 (200 mg) idi.Bulgular: Kontrol grubu ile karşılaştırıldığında, C1 50, 100, and 200 mg kg−1 dozlarda COX- 1 (hepsi için P < 0,01) veCOX-2 enzim aktivitesini (hepsi için P < 0.01) önemli ölçüde azalttı. C1’in tüm dozlarda COX-1 ve COX-2 aktiviteleriüzerine olan inhibitor etkileri nimesulidinkine benzerdi. Rofekoksib ile karşılaştırıldığında, C1 molekülü 200 mg kg−1dozda hem COX-1 hem de COX-2 aktivitelerini inhibe ederken (her ikisi için P < 0,01) 100 mg kg−1 dozda yalnızcaCOX-1 aktivitesini önemli olarak inhibe ettiği gözlendi (P < 0,05). 50 ve 100 mg kg−1 dozlarda C1 in COX-1 aktivitesiüzerine olan etkisi indometazin ile karşılaştırıldığında daha zayıf olduğu bulundu (sırası ile P < 0,01 ve P < 0,05).Sonuç: C1 molekülünün antiinflamatuar etkisinin olduğu ve bu COX-2 seçiciliğinin indometazin ve nimesulitten dahakuvvetli ancak rofekoksibten daha zayıf olduğu söylenebilir.

Anahtar Kelimeler:

3-Benzoil-1-metil-4-fenil-4-piperidinol-hidroklorür, COX enzimleri, inflamasyon

The effects of 3-benzoyl-1-methyl-4-phenyl-4- piperidinolhydrochloride (C1), indomethacin, nimesulide and rofecoxib on cyclooxygenase activities in carrageenan-induced paw edema model

The aim of this study was to investigate the effects of 3-benzoyl-1-methyl-4-phenyl-4-piperidinol-hydrochloride (C1), which is a structural and also non-classical isomer of bis Mannich base, bis (3-aryl-3-oxo-propyl) methylamine hydrochlorides (B1), on cyclooxygenase (COX) activities in 48 rats with inflammation by using carrageenan-induced paw edema, and to compare its effect with other non-steroidal anti-inflammatory drugs (NSAIDs). Materials and methods: Experimental animals were supplied by the Center of Experimental Research and Practice in Ataturk University. The animals were housed and fed in the laboratory (normal room temparature, food and water) under standard conditions. Rats were randomly assigned to eight groups (n = 6); control, intact, indomethacin, nimesulide, rofecoxib, C1 (50 mg), C1 (100 mg), and C1(200 mg). Results: C1 significantly inhibited COX-1 (P < 0.01 for all) and COX-2 (P < 0.01 for all) activities at the doses of 50, 100, and 200 mg kg-1 when compared to control group. The inhibitory effect of C1 on COX-1 and COX-2 activities at all doses was similar to those of nimesulide. While C1 at 200 mg kg-1 significantly inhibited COX-1 and COX-2 activities (P < 0.01 for both), at C1 100 mg kg-1 significantly inhibited only COX-1 activity in comparison to rofecoxib (P < 0.05). Inhibitory effects of C1 on COX-1 activity at the doses of 50 and 100 mg kg-1 were significantly weaker when compared to indomethacin (P < 0.01 and P < 0.05, respectively). Conclusion: It may be claimed that C1 has an anti-inflammatory effect, and its COX-2 selectivity is stronger than indomethacin and nimesulide but weaker than rofecoxib.

Keywords:

COX enzymes, inflammation, : 3-benzoyl-1-methyl-4-phenyl-4-piperidinol-hydrochloride,

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