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

GÜL, HALİSE İNCİ; AKSOY, Hülya; DEMİRCAN, Berna; ŞAHİN, Yaşar Nuri; Suleyman, Halis

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

Yaşar Nuri ŞAHİN, (Atatürk Üniversitesi, Tıp Fakültesi, Biyokimya Anabilim Dalı, Erzurum, Türkiye)

Berna DEMİRCAN, (Atatürk Üniversitesi, Tıp Fakültesi, Biyokimya Anabilim Dalı, Erzurum, Türkiye)

Halis SÜLEYMAN, (Atatürk Üniversitesi, Tıp Fakültesi, Farmakoloji Anabilim Dalı, Erzurum, Türkiye)

Hülya AKSOY, (Atatürk Üniversitesi, Tıp Fakültesi, Biyokimya Anabilim Dalı, Erzurum, Türkiye)

Halise İnci GÜL (Atatürk Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, Erzurum, Türkiye)

Turkish Journal of Medical Sciences

0 0

Yıl: 2010 Cilt: 40 Sayı: 5 Sayfa Aralığı: 723 - 728 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

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

Öz:

Amaç: Çalışmanın amacı 3-benzoil-1-metil-4-fenil-4-piperidinol-hidroklorür (C1) molekülünün karagenin ile oluşturulmuş pençe ödemi inflamasyonu modelinde siklooksijenaz (COX) enzim aktiviteleri üzerine etkilerini araştırmak ve 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) ve COX-2 enzim aktivitesini (hepsi için P < 0.01) önemli ölçüde azalttı. C1’in tüm dozlarda COX-1 ve COX-2 aktiviteleri üzerine 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 yalnızca COX-1 aktivitesini önemli olarak inhibe ettiği gözlendi (P < 0,05). 50 ve 100 mg kg −1 dozlarda C1 in COX-1 aktivitesi üzerine 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 daha kuvvetli ancak rofekoksibten daha zayıf olduğu söylenebilir.

Anahtar Kelime:

Konular: Biyoloji Biyokimya ve Moleküler Biyoloji

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

Öz:

Abstract: 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.

Anahtar Kelime:

Konular: Biyoloji Biyokimya ve Moleküler Biyoloji

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Ferraz JG, Sharkey KA, Reuter BK, Asfaha S, Tigley AW, Brown ML et al. Induction of cyclooxygenase 1 and 2 in the rat stomach during endotoxemia: role in resistance to damage. Gastroenterology 1997; 113: 195-204.
2. Okudur SS, Özer MT, Demirbaş S, Kalemoğlu M, Harlak A, Coşkun K et al. Prognostic importance of increased cyclooxygenase-2 levels in colorectal carcinomas: A 5-year single-institution study. EAJM 2008; 40: 6-9
3. Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A 2002; 99: 13926-13931.
4. Bombardier C. An evidence-based evaluation of the gastrointestinal safety of coxibs. Am J Cardiol 2002; 89: 3-9.
5. Süleyman H, Gül HI, Asoğlu M. Anti-inlammatory activity of 3-benzoyl-1-methyl-4-phenyl-4-piperidinol hydrochloride. Pharmacol Res 2003; 47: 471-475.
6. Suleyman H, Gul HI, Gul M, Alkan M, Gocer F. Anti- inlammatory activity of bis(3-aryl-3-oxo-propyl) methylamine hydrochloride in rat. Biol Pharm Bull 2007; 30: 63-67.
7. Gul HI, Yerdelen KO, Das U, Gul M, Pandit B, Li PK, Dimmock JR. Synthesis and cytotoxicity of novel 3-aryl-1-(3'- dibenzylaminomethyl-4'-hydroxyphenyl)-propenones and related compounds. Chem Pharm Bull (Tokyo). 2008; 56: 1675- 1681.
8. Gul HI, Cizmecioglu M, Zencir S, Gul M, Canturk P, Atalay M, Topcu Z. Cytotoxic activity of 4'-hydroxychalcone derivatives against Jurkat cells and their efects on mammalian DNA topoisomerase I. J Enzyme Inhib Med Chem. 2009; 24: 804-807.
9. Köksal M, Gökhan N, Küpeli E, Yesilada E, Erdogan H. Analgesic and antiinlammatory activities of some new Mannich bases of 5-nitro-2-benzoxazolinones. Arch Pharm Res. 2007; 30: 419-424.
10. Gul HI, Calls U, Ozturk Z, Tutar E, Calikiran L. Evaluation of anticonvulsant activities of bis(3-aryl-3-oxo-propyl) ethylamine hydrochlorides and 4-aryl-3-arylcarbonyl-1-ethyl-4-piperidinol hydrochlorides. Arzneimittelforschung. 2007; 57: 133-136.
11. Gul HI, Suleyman H, Gul M. Evaluation of the anti- inlammatory activity of N,N '-bis(3-dimethylamino-1-phenyl- propylidene) hydrazine dihydrochloride. Pharmaceutical Biology 2009; 47: 968-972.
12. Chen HT, Jing YK, Ji ZZ, Zhang BF. Synthesis and antiinlammatory and anticancer activities of 2-(E)-(un) substituted benzylidene cyclopentanones and their Mannich base hydro chlorides. Yao Xue Xue Bao 1991; 26: 183-192.
13. Zhao SZ, Reynolds MW, Lejkowith J, Whelton A, Arellano FM. A comparison of renal-related adverse drug reactions between rofecoxib and celecoxib, based on the World Health Organization/Uppsala Monitoring Centre safety database. Clin her 2001; 23: 1478-1491.
14. Tomlinson A, Appleton I, Moore AR, Gilroy DW, Willis D, Mitchell JA, Willoughby DA. Cyclo-oxygenase and nitric oxide synthase isoforms in rat carrageenin-induced pleurisy. Br J Pharmacol 1994; 113: 693-698.
15. Kataoka H, Horie Y, Koyama R, Nakatsugi S, Furukawa M. Interaction between NSAIDs and steroid in rat stomach: safety of nimesulide as a preferential COX-2 inhibitor in the stomach. Dig Dis Sci 2000; 45: 1366-1375.
16. Cullen L, Kelly L, Connor SO, Fitzgerald DJ. Selective cyclooxygenase-2 inhibition by nimesulide in man. J Pharmacol Exp her 1998; 287: 578-582.
17. Hawkey CJ. COX-2 inhibitors. Lancet 1999; 353: 307 –314.
18. Buttgereit F, Burmester GR, Simon LS. Gastrointestinal toxic side efects of nonsteroidal anti-inlammatory drugs of and cyclooxygenase-2-speciic inhibitors. Am J Med 2001; 19: 13S- 19S.
19. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. New England Journal of Medicine 2005; 352: 1092–1102.
20. Patrignani P. Nonsteroidal anti-inlammatory drugs, COX-2 and colorectal cancer. Toxicol Lett. 2000; 112-113: 493-498.

APA	ŞAHİN Y, DEMİRCAN B, Suleyman H, AKSOY H, GÜL H (2010). 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. , 723 - 728.
Chicago	ŞAHİN Yaşar Nuri,DEMİRCAN Berna,Suleyman Halis,AKSOY Hülya,GÜL HALİSE İNCİ 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. (2010): 723 - 728.
MLA	ŞAHİN Yaşar Nuri,DEMİRCAN Berna,Suleyman Halis,AKSOY Hülya,GÜL HALİSE İNCİ 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. , 2010, ss.723 - 728.
AMA	ŞAHİN Y,DEMİRCAN B,Suleyman H,AKSOY H,GÜL H 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. . 2010; 723 - 728.
Vancouver	ŞAHİN Y,DEMİRCAN B,Suleyman H,AKSOY H,GÜL H 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. . 2010; 723 - 728.
IEEE	ŞAHİN Y,DEMİRCAN B,Suleyman H,AKSOY H,GÜL H "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." , ss.723 - 728, 2010.
ISNAD	ŞAHİN, Yaşar Nuri vd. "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". (2010), 723-728.

APA	ŞAHİN Y, DEMİRCAN B, Suleyman H, AKSOY H, GÜL H (2010). 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. Turkish Journal of Medical Sciences, 40(5), 723 - 728.
Chicago	ŞAHİN Yaşar Nuri,DEMİRCAN Berna,Suleyman Halis,AKSOY Hülya,GÜL HALİSE İNCİ 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. Turkish Journal of Medical Sciences 40, no.5 (2010): 723 - 728.
MLA	ŞAHİN Yaşar Nuri,DEMİRCAN Berna,Suleyman Halis,AKSOY Hülya,GÜL HALİSE İNCİ 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. Turkish Journal of Medical Sciences, vol.40, no.5, 2010, ss.723 - 728.
AMA	ŞAHİN Y,DEMİRCAN B,Suleyman H,AKSOY H,GÜL H 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. Turkish Journal of Medical Sciences. 2010; 40(5): 723 - 728.
Vancouver	ŞAHİN Y,DEMİRCAN B,Suleyman H,AKSOY H,GÜL H 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. Turkish Journal of Medical Sciences. 2010; 40(5): 723 - 728.
IEEE	ŞAHİN Y,DEMİRCAN B,Suleyman H,AKSOY H,GÜL H "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." Turkish Journal of Medical Sciences, 40, ss.723 - 728, 2010.
ISNAD	ŞAHİN, Yaşar Nuri vd. "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". Turkish Journal of Medical Sciences 40/5 (2010), 723-728.