• MeSH
• hypertriglyceridemie genetika   MeSH
• krysa rodu rattus MeSH
• mastné kyseliny chemie   metabolismus   MeSH
• stárnutí MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

The aim of this study was to determine the effects of insulin infusion on oxidative stress induced by acute changes in glycemia in non-stressed hereditary hypertriglyceridemic rats (hHTG) and Wistar (control) rats. Rats were treated with glucose and either insulin or normal saline infusion for 3 hours followed by 90 min of hyperglycemic (12 mmol/l) and 90 min of euglycemic (6 mmol/l) clamp. Levels of total glutathione (GSH), oxidized glutathione (GSSG) and total antioxidant capacity (AOC) were determined to assess oxidative stress. In steady states of each clamp, glucose infusion rate (GIR) was calculated for evaluation of insulin sensitivity. GIR (mg.kg-1.min-1) was significantly lower in hHTG in comparison with Wistar rats; 25.46 (23.41 - 28.45) vs. 36.30 (27.49 - 50.42) on glycemia 6 mmol/l and 57.18 (50.78 - 60.63) vs. 68.00 (63.61 - 85.92) on glycemia 12 mmol/l. GSH/GSSG ratios were significantly higher in hHTG rats at basal conditions. Further results showed that, unlike in Wistar rats, insulin infusion significantly increases GSH/GSSG ratios in hHTG rats: 10.02 (9.90 - 11.42) vs. 6.01 (5.83 - 6.43) on glycemia 6 mmol/l and 7.42 (7.15 - 7.89) vs. 6.16 (5.74 - 7.05) on glycemia 12 mmol/l. Insulin infusion thus positively influences GSH/GSSG ratio and that way reduces intracellular oxidative stress in insulin-resistant animals.

• Klíčová slova
• Clamp, Oxidative stress, Insulin, Rat,
• MeSH
• antioxidancia metabolismus   MeSH
• dusík močoviny v krvi MeSH
• financování organizované MeSH
• glutathion metabolismus   MeSH
• glykemický clamp MeSH
• hypertriglyceridemie genetika   krev   MeSH
• inzulin krev   MeSH
• krevní glukóza metabolismus   MeSH
• krysa rodu rattus MeSH
• metabolický syndrom genetika   metabolismus   MeSH
• oxidační stres fyziologie   MeSH
• potkani Wistar MeSH
• potravinová deprivace MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• sérový albumin metabolismus   MeSH
• triglyceridy krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

OBJECTIVES: The aim of this study was to investigate whether rosuvastatin affects expression and activity of rat CYP2C6. This cytochrome P450 is considered to be a counterpart of human CYP2C9, which metabolizes many drugs, including diclofenac, ibuprofen or warfarin. DESIGN: Male hereditary hypertriglyceridemic (HHTg) rats were fed standard laboratory diet (STD) or high cholesterol diet (HCD: STD + 1% of cholesterol w/w + 10% of lard fat w/w) for 21 days. A third group of rats were fed high a cholesterol diet with rosuvastatin added (0.03% w/w). Expression of CYP2C6 was measured in liver samples using real-time PCR (mRNA level) and Western blotting (protein level). Formation of diclofenac metabolites (typical enzyme activity of CYP2C6) was analyzed using HPLC with UV detection. RESULTS: Administration of rosuvastatin to HHTg rats resulted in significantly increased mRNA expression and enzyme activity in HCD-fed animals; changes of CYP2C6 protein were non-significant. These results suggest that CYP2C6 expression and activity are positively affected by rosuvastatin in hereditary hypertriglyceridemic rats after intake of HCD. CONCLUSION: The results presented open the possibility that in humans, rosuvastatin may affect the metabolism of many drugs by influencing expression and activity of CYP2C6 (counterpart of human CYP2C9). Further studies are needed to elucidate the effects of this statin on CYP2C9 in humans.

• MeSH
• aromatické hydroxylasy antagonisté a inhibitory   metabolismus   MeSH
• cholesterol dietní farmakologie   MeSH
• fluorbenzeny farmakologie   MeSH
• genetická transkripce účinky léků   MeSH
• hyperlipoproteinemie typ IV farmakoterapie   genetika   metabolismus   MeSH
• jaterní mikrozomy účinky léků   enzymologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• mutantní kmeny potkanů MeSH
• potkani Wistar MeSH
• pyrimidiny farmakologie   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• statiny farmakologie   MeSH
• steroid-21-hydroxylasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• sulfonamidy farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hypertriglyceridemia and hypertension seem to be very important cardiovascular risk factors. The Prague hereditary hypertriglyceridemic (hHTG) rat was developed as a model of human hypertriglyceridemia. It was demonstrated that these rats are not obese, they are hypertensive and insulin resistant and they have some disturbances in glucose metabolism. Several QTLs were identified for blood pressure, its particular components (dependent on major vasoactive systems) and plasma triglycerides throughout the genome of hHTG rats by using of F(2) hybrids strategy. It is evident that hHTG rats are a suitable model for the study of metabolic disturbances in relation to blood pressure as well as for the search of genetic determinants of these abnormalities. Numerous abnormalities of blood pressure regulation as well as alterations in the structure and function of cardiovascular apparatus (heart, conduit and resistance arteries) were found in hHTG rats. A special attention was paid to possible changes in the efficiency of various vasoactive systems such as nitric oxide, renin-angiotensin-aldosterone system and sympathetic nervous system, which seem to contribute substantially to cardiovascular and/or metabolic abnormalities observed in Prague hereditary hypertriglyceridemic rats.

• MeSH
• hypertenze genetika   metabolismus   patofyziologie   MeSH
• hypertriglyceridemie genetika   metabolismus   patofyziologie   MeSH
• inzulinová rezistence genetika   MeSH
• krysa rodu rattus * MeSH
• lidé MeSH
• metabolický syndrom genetika   metabolismus   MeSH
• modely nemocí na zvířatech * MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus * MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• fosfolipidy metabolismus   MeSH
• hypertriglyceridemie MeSH
• inzulin metabolismus   MeSH
• krysa rodu rattus MeSH
• mastné kyseliny MeSH
• svaly metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

High blood pressure, increased level of cholesterol, diabetes, hypertriglyceridemia and obesity are risk factors accompanied metabolic syndrome. The aim of the study was to compare geometry of carotid artery (AC) of 3-week-old (3w) and 52-week-old (52w) hereditary hypertriglyceridemic rats (hHTG) and spontaneously hypertensive rats (SHR) which represent a genetic model of human essential hypertension with age-matched Wistar rats. After sacrificing the rats were perfused with a glutaraldehyde fixative under the pressure 90 mm Hg (3w) and 120 mm Hg (52w) for 10 min via cannula placed into left ventricle. Middle part of AC was excised and processed according to standard electron microscopy procedure. Geometry of AC was evaluated in light microscopy. SHR vs. Wistar rats: BP of 3w did not differ, in 52w it was increased; cardiac hypertrophy was found in both ages; wall thickness (WT) and cross sectional area (CSA) in 3w did not differ, in 52w both were increased; inner diameter (ID) in 3w and 52w was decreased; WT/ID was increased in both ages. Hereditary HTG vs. Wistar rats: BP was increased in both periods; cardiac hypertrophy was observed in 3w; WT in 3w was decreased, in 52w it was increased; CSA and ID were decreased in both ages; WT/ID was increased only in 52w. Discrepancies between development of BP, cardiac hypertrophy in SHR and hHTG rats were observed. Alterations of BP were not in harmony with alterations in geometry of carotid arteries in both SHR and hHTG rats. We suggest that BP is not the main stimuli evoked hemodynamic and structural alterations of cardiovascular system in ontogenic development of SHR and hHTG rats.

• MeSH
• arteriae carotides patologie   MeSH
• hypertenze patologie   patofyziologie   MeSH
• hypertriglyceridemie patologie   patofyziologie   MeSH
• krysa rodu rattus MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

• MeSH
• hypertriglyceridemie genetika   MeSH
• játra metabolismus   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• lipidy biosyntéza   MeSH
• modely nemocí na zvířatech MeSH
• triglyceridy krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH

• Klíčová slova
• HHTg potkani,
• MeSH
• anticholesteremika MeSH
• antioxidancia MeSH
• flavonoidy terapeutické užití   MeSH
• hydroxyethylrutosid * analogy a deriváty   farmakologie   terapeutické užití   MeSH
• inzulinová rezistence MeSH
• krysa rodu rattus MeSH
• lipidy analýza   krev   MeSH
• metabolický syndrom farmakoterapie   MeSH
• oxidační stres účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

Parallel glucose measurements in blood and other different tissues give us knowledge about dynamics of glycemia changes, which depend on vascularization, distribution space and local utilization by tissues. Such information is important for the understanding of glucose homeostasis and regulation. The aim of our study was to determine the time-lag between blood, brain, and adipose tissue during rapid glucose changes in a male hHTG rat (n=15). The CGMS sensor Guardian RT (Minimed/Medtronic, USA) was inserted into the brain and into the abdominal subcutaneous tissue. Fixed insulin and variable rate of glucose infusion was used to maintain euglycemia during sensor calibration period. At 0 min, 0.5 g/kg of bolus of glucose was administered, and at 50 min, 5 IU/kg of bolus of insulin was administered. Further glucose and insulin infusion was stopped at this time. The experiment was finished at 130 min and animals were euthanized. The time-shift between glycemia changes in blood, brain, and subcutaneous tissue was calculated by identification of the ideal correlation function. Moreover, the time to achieve 90 % of the maximum glucose excursion after intervention (T90) was measured to compare our data with the literature. The time-lag blood vs. brain and blood vs. subcutaneous tissue was 10 (10; 15) min and 15 (15; 25) min, respectively. The difference was statistically significant (P=0.01). T90 after glucose bolus in brain and subcutaneous tissue was 10 min (8.75; 15) and 15 min (13.75; 21.25), respectively. T90 after insulin bolus in brain and subcutaneous tissue was 10 min (10; 15) and 20 min (20; 27.5), respectively. To the contrary, with literature, our results showed earlier glucose level changes in brain in comparison with subcutaneous tissue after glucose and insulin boluses. Our results suggest that glucose dynamics is different within monitored tissues under rapid changing glucose level and we can expect similar behavior in humans. Improved knowledge about glucose distribution and dynamics is important for avoiding hypoglycemia.

• MeSH
• glykemický index fyziologie   MeSH
• hypertriglyceridemie krev   diagnóza   genetika   MeSH
• krevní glukóza metabolismus   MeSH
• krysa rodu rattus MeSH
• monitorování fyziologických funkcí metody   trendy   MeSH
• mozek metabolismus   MeSH
• potkani Wistar MeSH
• subkutánní tkáň metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH