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

Activation of nuclear factor-κB (NF-κB) by increased production of reactive oxygen species (ROS) might induce transcription and expression of different antioxidant enzymes and also of nitric oxide synthase (NOS) isoforms. Thus, we aimed at studying the effect of NF-κB inhibition, caused by JSH-23 (4-methyl-N (1)-(3-phenyl-propyl)-benzene-1,2-diamine) injection, on ROS and NO generation in hereditary hypertriglyceridemic (HTG) rats. 12-week-old, male Wistar and HTG rats were treated with JSH-23 (bolus, 10 μmol, i.v.). After one week, blood pressure (BP), superoxide dismutase (SOD) activity, SOD1, endothelial NOS (eNOS), and NF-κB (p65) protein expressions were higher in the heart of HTG rats compared to control rats. On the other hand, NOS activity was decreased. In HTG rats, JSH-23 treatment increased BP and heart conjugated dienes (CD) concentration (measured as the marker of tissue oxidative damage). Concomitantly, SOD activity together with SOD1 expression was decreased, while NOS activity and eNOS protein expression were increased significantly. In conclusion, NF-κB inhibition in HTG rats led to decreased ROS degradation by SOD followed by increased oxidative damage in the heart and BP elevation. In these conditions, increased NO generation may represent rather a counterregulatory mechanism activated by ROS. Nevertheless, this mechanism was not sufficient enough to compensate BP increase in HTG rats.

• MeSH
• exprese genu účinky léků   MeSH
• fenylendiaminy farmakologie   MeSH
• glutathion analýza   MeSH
• hyperlipoproteinemie typ IV patologie   veterinární   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• myokard metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• srdeční komory metabolismus   MeSH
• superoxiddismutasa genetika   metabolismus   MeSH
• synthasa oxidu dusnatého, typ III genetika   metabolismus   MeSH
• synthasa oxidu dusnatého genetika   metabolismus   MeSH
• tělesná hmotnost účinky léků   MeSH
• transkripční faktor RelA genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 4-methyl-N1-(3-phenylpropyl)benzene-1,2-diamine MeSH Prohlížeč
• fenylendiaminy MeSH
• glutathion MeSH
• oxid dusnatý MeSH
• reaktivní formy kyslíku MeSH
• superoxiddismutasa MeSH
• synthasa oxidu dusnatého, typ III MeSH
• synthasa oxidu dusnatého MeSH
• transkripční faktor RelA MeSH