Phenotyping determination of CYP1A2 enzyme activity using caffeine in sheep
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Dosyalar
Tarih
2011
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Selçuk Üniversitesi Veterinerlik Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Prob ilaç olarak kafein (KF) kullanılarak Morkaraman (MK), Akkaraman (AK) ve Anadolu Merinosu (AM) koyun ırklarında in vivo CYP1A2 enzim aktivitesini karşılaş- tırmak ve pratikte CYP1A2 aktivitesini belirlemede plazma metabolik oranlarının (MO) geçerliliğini ortaya koymaktır. Gereç ve Yöntem: Kafein tüm koyunlara 5 mg/kg dozda damar içi yolla uygulandı. Plazma KF ve paraksantin (PK) düzeyleri yüksek performanslı sıvı kromatografi kullanılarak ölçüldü. CYP1A2 fenotipi PK ve KF’nin plazma konsantrasyon-zaman eğrisinin altındaki alanlar (EAA) arasındaki oran [(PK/KF)EAA] ve KF uygulamasından sonra 3-16. saatlerde PK ve KF’nin plazma konsantrasyonları arasındaki oranlar [(PK/KF)MO?3-16 saat] kullanılarak ölçüldü. Pratikte tek bir kan örneği üzerinden CYP1A2 fenotipini araştırmak için (PK/KF)MO?3-16 saat ve (PK/KF)EAA oranları arasındaki ilişkiler belirlendi. Bulgular: CYP1A2 fenotipinin belirlenmesinde (PK/KF) MO?3-16 saat oranlarının içinde en güvenilir örnekleme zamanının KF uygulamasından sonraki 10. saat olduğu tespit edildi. (PK/KF)MO?10 h ve (PX/KF)EAA oranları koyun ırkları arasında benzerdi (p>0.05). Öneri: Koyunda plazma (PX/KF)MO?10 h oranı CYP1A2 fenotipinin belirlenmesinde hızlı ve basit bir test olarak kullanı- labilir. Ancak, bu çalışmanın sonuçlarına göre CYP1A2 enziminin MK, AK ve AM koyun ırkları arasında substratı durumundaki ilaç ve çevresel bileşiklerin etkilerinde görülen farklılıklarda klinik yönden öneminin olmayabileceği anla- şılmaktadır.
Aim: The aims of this study were to determine the validity of the plasma metabolic ratios (MR) to investigate the CYP1A2 activity in practice and to compare in vivo CYP1A2 enzyme activity using caffeine (CF) as a probe in Morkaraman (MK), Akkaraman (AK) and Anatolia Merino (AM) sheep breeds. Materials and Methods: Caffeine was administered as a single dose of 5 mg/kg b.w. by the intravenous in MK, AK and AM sheep breeds. The plasma levels of CF and paraxanthine (PX) were measured using high-performance liquid chromatography. CYP1A2 phenotyping was measured using the ratio [(PX/CF)AUC] between areas under the plasma concentration-time curve (AUCs) of PX and CF and the ratios [(PX/CF)MR?3-16 h] between plasma concentrations of PX and CF at 3 to 16 h after CF administration. Correlations between the plasma (PX/CF)MR?3-16 h and (PX/CF)AUC ratios were determined to investigate of the CYP1A2 phenotyping by single blood sampling in practice. Results: It was determined that the more reliable sampling time within the plasma (PX/CF)MR?3-16 h ratios in the determination of the CYP1A2 phenotyping was 10 h after CF administration. (PX/CF)MR?10 h and (PX/CF)AUC ratios were similar (p>0.05) among sheep breeds. Conclusion: The plasma (PX/CF)MR?10 h ratio might be used as a rapid and simple screening test for CYP1A2 phenotyping in sheep. CYP1A2 enzyme may not be clinically important in the observed differences to the effects of drugs and environmental chemicals with its substrates among MK, AK and AM sheep breeds.
Aim: The aims of this study were to determine the validity of the plasma metabolic ratios (MR) to investigate the CYP1A2 activity in practice and to compare in vivo CYP1A2 enzyme activity using caffeine (CF) as a probe in Morkaraman (MK), Akkaraman (AK) and Anatolia Merino (AM) sheep breeds. Materials and Methods: Caffeine was administered as a single dose of 5 mg/kg b.w. by the intravenous in MK, AK and AM sheep breeds. The plasma levels of CF and paraxanthine (PX) were measured using high-performance liquid chromatography. CYP1A2 phenotyping was measured using the ratio [(PX/CF)AUC] between areas under the plasma concentration-time curve (AUCs) of PX and CF and the ratios [(PX/CF)MR?3-16 h] between plasma concentrations of PX and CF at 3 to 16 h after CF administration. Correlations between the plasma (PX/CF)MR?3-16 h and (PX/CF)AUC ratios were determined to investigate of the CYP1A2 phenotyping by single blood sampling in practice. Results: It was determined that the more reliable sampling time within the plasma (PX/CF)MR?3-16 h ratios in the determination of the CYP1A2 phenotyping was 10 h after CF administration. (PX/CF)MR?10 h and (PX/CF)AUC ratios were similar (p>0.05) among sheep breeds. Conclusion: The plasma (PX/CF)MR?10 h ratio might be used as a rapid and simple screening test for CYP1A2 phenotyping in sheep. CYP1A2 enzyme may not be clinically important in the observed differences to the effects of drugs and environmental chemicals with its substrates among MK, AK and AM sheep breeds.
Açıklama
Anahtar Kelimeler
Kafein, CYP1A2 aktivitesi, koyun, ırk, Caffeine, CYP1A2 activity, sheep, breed
Kaynak
Eurasian Journal of Veterinary Sciences
WoS Q Değeri
Scopus Q Değeri
Cilt
27
Sayı
1
Künye
Uney, K., Tras, B., (2011).Phenotyping determination of CYP1A2 enzyme activity using caffeine in sheep. Eurasian Journal of Veterinary Sciences. 27 (1), 27-32.
