Metabolic syndrome (MetS) is a cluster of risk factors that increase the likelihood of developing cardiovascular, metabolic and other diseases. The pharmacological management of MetS often involves polypharmacy, making it essential to understand how drug-metabolising enzymes, transporters, transcription factors and other proteins involved are affected under different metabolic conditions. This study investigated the relative mRNA expression of key hepatic and intestinal genes involved in drug metabolism, including Cyp1a2, Cyp3a23, Cyp2d1, Cyp2c11, Cyp2c6, Cyp2e1, Cyp7a1, Cyp2b1, Cyp2a1, Abcg5, Abcg8, Abcb1, Nr1i3, Nr1i2, Ahr, Gsta1 and Comt, in four nonobese rat models of MetS: hereditary hypertriglyceridaemic (HHTg), spontaneously hypertensive rat (SHR), SHR expressing transgenic human C-reactive protein (SHR-CRP), and bilaterally ovariectomised Wistar (W-OVX), compared to Wistar controls. Gene expression was quantified by RT-PCR with data normalised using the ΔΔCt method. Between the models studied, measurements showed significant differences in the liver. The upregulation of Cyp2c6 and Cyp3a23 was observed only in SHR; upregulated Cyp2d1 was found in SHR as well as in HHTg rats. The downregulated Cyp1a2 was measured in a condition of hypertriglyceridemia, postmenopause or hypertension. These findings highlight model-specific alterations in gene expression that may affect drug metabolism and interactions. The HHTg may be, in particular, a suitable model for preclinical studies focusing on intestinal drug-drug interactions in MetS-related conditions.

• Klíčová slova
• drug metabolism, metabolic syndrome, rat model,
• MeSH
• játra metabolismus   enzymologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• membránové transportní proteiny * genetika   metabolismus   MeSH
• messenger RNA * metabolismus   genetika   MeSH
• metabolický syndrom * genetika   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• receptory cytoplazmatické a nukleární * genetika   metabolismus   MeSH
• systém (enzymů) cytochromů P-450 * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• membránové transportní proteiny * MeSH
• messenger RNA * MeSH
• receptory cytoplazmatické a nukleární * MeSH
• systém (enzymů) cytochromů P-450 * MeSH