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Hepatic mRNA Expression (hepatic + mrna_expression)
Selected AbstractsEffects of intrauterine undernutrition on the expression of CYP3A23/3A1, PXR, CAR and HNF4, in neonate ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2008Shaoqing Ni Abstract Cytochrome P-450 3A (CYP3A) together with its nuclear receptors plays a critical role in drug metabolism. The present study investigated the effects of undernutrition in utero on hepatic mRNA and protein expression of the enzyme CYP3A23/3A1 and nuclear receptors including pregnane X receptor (PXR; NR1I2), constitutive androstane receptor (CAR; NR1I3) and nuclear factor-4alpha (HNF4,; HNF4A) in neonatal rats. At gestational day 2, pregnant rats were randomly divided into two groups: nourished (fed ad libitum) and undernourished (50% of nourished group). The pups delivered by nourished rats were designated as the normal-birth-weight group (NBW, n=15) and those delivered by undernourished rats were designated as the low-birth-weight group (LBW, n=15). Hepatic mRNA expression was detected by quantitative real-time PCR and the corresponding protein expression was examined by immunohistochemistry (IHC). Compared with NBW pups, LBW pups tended to have lower mRNA expression levels of CYP3A23/3A1, PXR and CAR but higher levels of HNF4,. Only the CAR mRNA expression differences were significant (p<0.05). mRNA expression of CYP3A23/3A1 correlated with that of HNF4, in both the LBW(r=0.808, p=0.007) and NBW (r=0.452, p=0.012) groups. CYP3A23/3A1 and CAR protein expression differed between the two groups (CYP3A23/3A1, ,2=7.87, p=0.005; CAR, ,2=12.069, p=0.001). In conclusion, these findings suggest that undernutrition may influence the mRNA expression of CAR and protein expression of both CYP3A23/3A1 and CAR in neonatal rats. Since CYP3A23/3A1 and CAR are critically involved in drug metabolism, these results may have clinical implications for optimal medication in LBW children. Copyright © 2008 John Wiley & Sons, Ltd. [source] Comparative study between the effect of the peroxisome proliferator activated receptor-, ligands fenofibrate and n-3 polyunsaturated fatty acids on activation of 5,-AMP-activated protein kinase-,1 in high-fat fed ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2009Tarek M. Kamal Motawi Abstract Objectives Obesity is a risk factor for type 2 diabetes mellitus. It results from an energy imbalance in which energy intake exceeds energy expenditure. The cellular fuel gauge 5,-AMP-activated protein kinase (AMPK) is a heterotrimeric protein consisting of one catalytic subunit (,) and two non-catalytic subunits (, and ,), and approximately equal levels of ,1 and ,2 complexes are present in the liver. AMPK regulates metabolic pathways in response to metabolic stress and in particular ATP depletion to switch on energy-producing catabolic pathways such as ,-oxidation of fatty acids and switch off energy-depleting processes such as synthesis of fatty acid and cholesterol. A high-fat diet alters AMPK-,1 gene expression in the liver and skeletal muscle of rats and results in body weight gain and hyperglycaemia. The aim of this study was to investigate and compare the potential effects of peroxisome proliferator-activated receptor (PPAR)-, agonists fenofibrate and n-3 polyunsaturated fatty acids (PUFAs) in modulation of AMPK-,1 activity in liver and skeletal muscle of high-fat diet fed rats. Methods Reverse transcription,polymerase chain reaction was used for determination of AMPK-,1 in liver and soleus muscle and both PPAR-, and CPT-1 in hepatic tissues. Serum, total cholesterol, triacylglycerol, fatty acid and fasting blood glucose were determined colorimetrically. Key findings Both PPAR-, agonists, fenofibrate and n-3 PUFA, increased the mRNA expression of AMPK-,1 activity in liver and skeletal muscle of obese diabetic rats. Fenofibrate was superior in its activation of hepatic mRNA expression of AMPK-, 1 to exert more lipolytic effect and body weight reduction, as estimated through the decrease of triacylglycerol output and serum levels of fatty acid on the one hand and the increase in CPT-1 mRNA expression, the key enzyme in ,-oxidation of fatty acid, on the other hand. n-3 PUFA activated AMPK-,1 mRNA expression in skeletal muscle much more than fenofibrate to reveal more hypoglycaemic effect. Conclusions The PPAR-, agonists fenofibrate and n-3 PUFA could efficiently activate AMPK-,1 mRNA expression in liver and skeletal muscle to exert body weight reduction and hypoglycaemic effect, respectively. [source] Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride-induced hepatic fibrosis in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2003Tzung-Yan Lee ABSTRACT Carbon tetrachloride (CCl4) is metabolized by cytochrome P450 to form a reactive trichloromethyl radical that triggers a chain of lipid peroxidation. These changes lead to cell injury, and chronic liver injury leads to excessive deposition of collagen in liver, resulting in liver fibrosis. The aim of this study was to evaluate the effects of long-term Salvia miltiorrhiza administration in CCl4 -induced hepatic injury in rats. Salvia miltiorrhiza (10, 25 or 50 mg kg,1 twice a day) was given for 9 weeks, beginning at the same time as the injections of CCl4. Rats receiving CCl4 alone showed a decreased hepatic glutathione level and an increased glutathione-S-transferase content. The hepatic thiobarbituratic acid-reactive substance levels were increased. CCl4 also caused a prominent collagen deposition in liver histology that was further supported by the increased hepatic mRNA expression of transforming growth factor-,1, tissue inhibitor of metallproteinase-1 and procollagen I. Salvia miltiorrhiza administration led to a dose-dependent increase in hepatic glutathione levels and a decrease in peroxidation products. Additionally, it reduced the mRNA expression of markers for hepatic fibrogenesis. In conclusion, long-term administration of Salvia miltiorrhiza in rats ameliorated the CCl4 -induced hepatic injury that probably related to a reduced oxidant stress and degree of hepatic fibrosis. [source] Beneficial effect of laserpitin, a coumarin compound from Angelica keiskei, on lipid metabolism in stroke-prone spontaneously hypertensive ratsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2005Hiroshi Ogawa Summary 1.,Recently, we found that 4-hydroxyderricin, one of the major chalcones in Angelica keiskei extract (an ethyl acetate extract from the yellow liquid of stems), suppressed increases in systolic blood pressure and reduced both serum very low-density lipoprotein levels and liver triglyceride content in stroke-prone spontaneously hypertensive rats (SHRSP). In the present study, we have isolated laserpitin, a characteristic coumarin, from the A. keiskei extract and examined the effect of dietary laserpitin on blood pressure and lipid metabolism in SHRSP. 2.,Six-week-old male SHRSP were fed diets containing 0.1% laserpitin for 7 weeks with free access to the diet and water. Bodyweight gain was reduced by dietary laserpitin after 4 weeks through to 7 weeks without any significant change in daily food intake. Serum total cholesterol, phospholipid and apolipoprotein (apo) E levels were significantly increased, which was due to significant increases in cholesterol, phospholipid and apoE contents in the low- and high-density lipoprotein (LDL and HDL, respectively) fractions. These results suggest that dietary laserpitin increases serum apoE-HDL levels. 3.,In the liver, significant decreases in relative liver weight and triglyceride content were found after treatment with laserpitin for 7 weeks. 4.,An investigation of hepatic mRNA expression of proteins involved in lipid metabolism indicated that a significant decrease in hepatic triglyceride lipase may be responsible for the increase in serum HDL levels and also indicated that a marked decrease in adipocyte determination and differentiation factor 1 may be responsible, at least in part, for the decrease in hepatic triglyceride content. 5.,In conclusion, dietary laserpitin produces increases in serum HDL levels, especially apoE-HDL, and decreases in the hepatic triglyceride content in SHRSP. [source] | ||||||||||