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Effect of Low and High-Dose Dexamethasone on CYP3A and P-glycoprotein Expression and Function in Mice

Eurasian Journal of Veterinary Sciences · Ocak 2025

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YÖKSİS Kayıtları
Effect of Low and High-Dose Dexamethasone on CYP3A and P-glycoprotein Expression and Function in Mice
Eurasian Journal of Veterinary Sciences · 2025 TR DİZİN
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Makale Bilgileri

DergiEurasian Journal of Veterinary Sciences
Yayın TarihiOcak 2025
Cilt / Sayfa41
Erişim🔓 Açık Erişim
Özet Dexamethasone, which acts on nuclear receptors, is used together with P-gp and Cyp3a4 substrates at different doses in the treatment of diverse diseases. The aim of the study is to determine the effect of different doses of dexamethasone on the expressions and functions of P-gp and Cyp3a4 (mouse homologues of Cyp3a4 are Cyp3a11 and Cyp3a13). Animals (n=54) were divided into 9 equal groups. The control group was given only water. (The second group received fexofenadine, the third group received midazolam, the fourth group received low-dose dexamethasone, and the fifth group received high-dose dexamethasone. Low dose dexamethasone was administered to the sixth and seventh groups, and high dose dexamethasone was administered to the eighth and ninth groups.) 24 hours after these applications, fexofenadine was administered to the sixth and eighth groups, and midazolam was administered to the seventh and ninth groups. Synthesis of mdr1a, mdr1b, Cyp3a11 and Cyp3a13 in the small intestine and liver were determined using RT-qPCR. Plasma concentrations of fexofenadine and midazolam were determined using HPLC-UV. The effect of dexamethasone on Cyp3a11 expression was determined to be dose-related, while its effect on P-gp expression was not dose-related. Midazolam, a CYP3A substrate, did not cause P-gp induction in the small intestine, but did cause P-gp induction in the liver. Fexofenadine and midazolam reduced the effect of dexamethasone on Cyp3a11 expression in the small intestine. Dexamethasone dose-dependently decreased the plasma concentration of midazolam and increased that of its metabolite. Dexamethasone caused a dose-independent decrease in plasma concentrations of fexofenadine. The effect of dexamethasone on P-gp expression is not dose-dependent, but its effect on Cyp3a11 ve Cyp3a13 expression is dose-dependent. Fexofenadine and midazolam caused a reduction in the effect of dexamethasone on Cyp3a11 expression in the small intestine.

Yazarlar (7)

1
H. Eser Faki
2
Gonca Sönmez
3
B. Traş
4
Kamil Üney
ORCID: 0000-0002-8674-4873
5
T. M. Parlak
6
Zeynep Ozdemir Kutahya
7
Hakan Akbayrak

Anahtar Kelimeler

Cyp3a4 Dexamethasone Dose Mice P-glycoprotein

Kurumlar

Çukurova Üniversitesi
Adana Turkey
Selçuk Tip Fakültesi
Konya Turkey
Selçuk Üniversitesi
Selçuklu Turkey