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Alterations in hepatic gene expressions of CYP2C11, CYP2C6V, and CYP2D3 enzymes in endotoxemic rats
(AVES, 2017) Ozer, Erdem K.; Kurtgoz, Serkan; Goktas, Mustafa T.; Karaca, Ragip O.; Caliskan, Metin; Bariskaner, Hulagu; Iskit, Alper B.
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 CYP-2C6V-mediated-drug metabolism. Therefore, drug dosage must be cautiously adjusted in the patients with endotoxemia and sepsis.