Search results for "45"
showing 10 items of 1896 documents
Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-α
2010
Estradiol (E2) acts on the endothelium to promote vasodilatation through the release of several compounds, including prostanoids, which are products of arachidonic acid metabolism. Among these, prostacyclin (PGI2) and thromboxane A2 (TXA2) exert opposite effects on vascular tone. The role of different estrogen receptors (ERs) in the PGI2/TXA2 balance, however, has not been fully elucidated. Our study sought to uncover whether E2 enhances basal production of PGI2 or TXA2 in cultured human umbilical vein endothelial cells (HUVECs), to analyze the enzymatic mechanisms involved, and to evaluate the different roles of both types of ERs (ERα and ERβ). HUVECs were exposed to E2, selective ERα (1,3…
Endogenous nitric oxide is responsible for the early loss of P450 in cultured rat hepatocytes
1998
AbstractLoss of P450 during the early hours of monolayer formation is known to be the more serious limitation of primary cultured hepatocytes as an adequate model for the study of drug metabolism, toxicity and P450 induction. This study reports that endogenous nitric oxide (NO) formation is activated shortly after isolation by the classical collagenase-based liver perfusion methods. Both rapid P450 loss and aerobic mitochondrial energy metabolism impairment – with subsequent changes on glucose metabolism – are directly related to the high local generation of the radical at this stage. These effects can be reverted by the sole addition of NO biosynthesis inhibitors during liver perfusion and…
Difference between Guinea Pig and Rat in the Liver Peroxisomal Response to Equivalent Plasmatic Level of Ciprofibrate
1996
Abstract Guinea pig was previously classified as a species nonresponsive to peroxisome proliferators. However, none of the previous reports was based on pharmacokinetic data. Here, after a comparative pharmacokinetic study between guinea pig and rat, we evaluate the guinea pig liver peroxisomal response to ciprofibrate, a hypolipemic agent and a potent peroxisome proliferator in rat. (1) Pharmacokinetic results show that plasmatic concentrations of ciprofibrate are equivalent in guinea pig and rat when guinea pigs are treated with ciprofibrate at 30 mg/kg twice a day and rats are treated at 3 mg/kg once a day. (2) The treatment of guinea pigs at 30 mg/kg twice a day for 2 weeks leads to a s…
Studies on the disposition, metabolism and hepatotoxicity of coumarin in the rat and Syrian hamster.
2002
The hepatotoxicity, metabolism and disposition of coumarin has been compared in male Sprague-Dawley rats and Syrian hamsters. The treatment of rats for 12, 24 and 42 weeks with diets containing 0.2 and 0.5% coumarin resulted in hepatotoxicity and increased relative liver weights. While levels of cytochrome P450 (CYP) and CYP-dependent enzymes were decreased, levels of reduced glutathione (GSH) and activities of UDP glucuronosyltransferase, gamma-glutamyltransferase and GSH S-transferase were increased. In contrast, coumarin produced few hepatic changes in the Syrian hamster. Following a single oral dose of 25 mg/kg [3-14C]coumarin, radioactivity was rapidly excreted by the rat and Syrian ha…
Absence of lipid peroxidation as determined by ethane exhalation in rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).
1985
The exhalation of ethane is widely used as an indicator of in vivo lipid peroxidation. To test the hypothesis that lipid peroxidative events are involved in the toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), we administered a lethal dose of TCDD (60 μg/kg), IP to male Sprague Dawley rats (160–180 g) and measured by gas chromatography the exhalation of ethane into the atmosphere of a closed all-glass exposure chamber. TCDD-treated rats exhaled only slightly more ethane than control rats at a single time point 7 days following TCDD administration. Since the exhalation of ethane is the net result of the endogenous production of the gas and its metabolic degradation, the latter was …
Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat model of streptozotocin-induced diabetes mellitus
2007
Abstract Objective HMG-CoA reductase inhibitors have been shown to upregulate GTP cyclohydrolase I (GTPCH-I), the key enzyme for tetrahydrobiopterin de novo synthesis and to normalize tetrahydrobiopterin levels in hyperglycemic endothelial cells. We sought to determine whether in vivo treatment with the HMG-CoA reductase inhibitor atorvastatin is able to upregulate the GTPCH-I, to recouple eNOS and to normalize endothelial dysfunction in an experimental model of diabetes mellitus. Methods and results In male Wistar rats, diabetes was induced by streptozotocin (STZ, 60mg/kg). In STZ rats, atorvastatin feeding (20mg/kg/d, 7 weeks), normalized vascular dysfunction as analyzed by isometric tens…
Murine tissue factor disulfide mutation causes a bleeding phenotype with sex specific organ pathology and lethality.
2019
Tissue factor is highly expressed in sub-endothelial tissue. The extracellular allosteric disulfide bond Cys186-Cys209 of human tissue factor shows high evolutionary conservation and in vitro evidence suggests that it significantly contributes to tissue factor procoagulant activity. To investigate the role of this allosteric disulfide bond in vivo, we generated a C213G mutant tissue factor mouse by replacing Cys213 of the corresponding disulfide Cys190-Cys213 in murine tissue factor. A bleeding phenotype was prominent in homozygous C213G tissue factor mice. Pre-natal lethality of 1/3rd of homozygous offspring was observed between E9.5 and E14.5 associated with placental hemorrhages. After b…
In-hospital death according to dementia diagnosis in acutely ill elderly patients: the REPOSI study.
2011
The aim of the study was to explore the association of dementia with in-hospital OBJECTIVE:The aim of the study was to explore the association of dementia with in-hospital death in acutely ill medical patients. METHODS: Thirty-four internal medicine and 4 geriatric wards in Italy participated in the Registro Politerapie SIMI-REPOSI-study during 2008. One thousand three hundred and thirty two in-patients aged 65 years or older were enrolled. Logistic regression models were used to evaluate the association of dementia with in-hospital death. Socio-demographic characteristics, morbidity (single diseases and the Charlson Index), number of drugs, and adverse clinical events during hospitalizatio…
Response of genetically obese Zucker rats to ciprofibrate, a hypolipidemic agent, with peroxisome proliferation activity as compared to Zucker lean a…
1993
Genetically obese Zucker (fa/fa) rats were used as an experimental model to study the effects of hypolipidemic agents on peroxisome proliferation; comparison was made with Zucker lean phenotype (Fa/-) and Sprague-Dawley strain/phenotype. The pharmacokinetics of a single administration of ciprofibrate (1 or 3 mg/kg), appeared to be similar in all strains/phenotypes. After a 2-week oral administration at the same dosages, there were dosage-related increases in hepatocellular peroxisomal yield and in the hepatic enzymes' cyanide-insensitive acyl-CoA oxidase and catalase. The peroxisomal yield was less increased in Zucker than in Sprague-Dawley rats, while the enzyme activities were similarly i…
The Effect of Indobufen on the Activities of Selected Rat Liver Phase I and Phase II Drug Metabolizing Enzymes, Peroxisomal β-oxidation and Hepatic G…
1994
Abstract Oral administration of indobufen to male rats for three days at daily doses of 5, 10 and 20 mg kg−1 resulted in no changes in liver total glutathione, cytosolic glutathione S-transferases or microsomal epoxide hydrolase. Reduced glutathione appeared slightly diminished to about 84% of control at the highest dose level. Microsomal cytochrome P450-dependent ethoxyresorufin O-de-ethylase and pentoxyresorufin de-alkylase activities were decreased to 64% (not significantly) and 67% of control at the lowest dose level. 6α- and 7α-Hydroxytestosterone activities were decreased to 67 and 68% of control at the highest dose level. Cyanide-insensitive peroxisomal fatty acid β-oxidation was inc…