Journal of Medical and Surgical Intensive Care Medicine 2017 , Vol 8, Issue 2
Alterations in Hepatic Gene Expressions of CYP2C11, CYP2C6V, and CYP2D3 Enzymes in Endotoxemic Rats
Erdem K. Özer 1 , Hülagü Barışkaner 1 , Serkan Kurtgöz 2 , Mustafa T. Göktaş 3 , Ragıp Ö. Karaca 4 , Alper B. İskit 4 , Metin Çalışkan 5
1Department of Medical Pharmacology, Selçuk University School of Medicine, Konya, Turkey
2Department of Medical Genetics, Süleyman Demirel University School of Medicine, Isparta, Turkey
3Department of Medical Pharmacology, Yıldırım Beyazıt University School of Medicine, Ankara, Turkey
4Department of Medical Pharmacology, Hacettepe University School of Medicine, Ankara, Turkey
5Department of Medical Genetics, Adnan Menderes University School of Medicine, Aydın, Turkey
DOI : 10.5152/dcbybd.2017.1552

Objective: Human cytochrome P450 2C9 (CYP2C9), CYP2C19, and CYP2D6 (corresponding to rat CYP2C11, CYP2C6V, and CYP2D3, respectively) are the major enzymes responsible for the metabolism of a wide range of drugs and chemicals. Changes in CYP efficiency are associated with disease susceptibility that can lead to drug toxicity or ineffective therapy. We aimed to examine the effects of lipopolysaccharide (LPS)-induced endotoxemia on gene expressions of hepatic microsomal CYP enzymes in rats.

Material and Methods: Male Wistar albino rats were allocated into two subgroups of control and LPS. Saline or LPS (10 mg/kg) of same volume (1 mL/kg) was intraperitoneally (i.p.) injected into rats. After 4 hours, liver tissues were removed. Hepatic mRNA expressions of the CYP enzymes were quantitatively analyzed using real-time polymerase chain reaction (PCR).

Results: Hepatic gene expressions of CYP2C11 and CYP2C6V decreased (3.35 and 2.25 fold, respectively) in the endotoxemic rats; however, CYP2D3 expression did not change.

Conclusion: Our results revealed that endotoxemia changes CYP2C11- and CYP2C6V-mediated drug metabolism. Therefore, drug dosage must be cautiously adjusted in the patients with endotoxemia and sepsis. 

Cite this article as: Özer EK, Kurtgöz S, Göktaş MT, et al. Alterations in hepatic gene expressions of CYP2C11, CYP2C6V, and CYP2D3 enzymes in endotoxemic rats. Yoğun Bakım Derg 2017; 8: 50-3.

Keywords : Endotoxemia, liver, gene expressions, cytochrome P450 enzymes