Search results for "REDUCTASE"
showing 10 items of 798 documents
Glutathione-dependent resistance of the European eel Anguilla anguilla to the herbicide molinate
2001
Eels of species Anguilla anguilla were exposed to 5/4 LC50 (41.8 mg/l) of the herbicide molinate for 96 h in a time to death (TTD) test. Glutathione content (GSx, GSH, GSSG), glutathione reductase (GR) and gamma-glutamyl transpeptidase (gamma-GT) activities were determined in the liver and muscle tissues of dead and surviving (intoxicated) animals and compared to control values (non-exposed eels). TTD was positively correlated to hepatic GSH, GSH:GSSG ratio, hepatic and muscular GR, but negatively correlated to muscular GSH, which was severely depleted. Furthermore, glutathione and enzyme activities were intercorrelated, especially GSH and GR. These results indicate that eels which were abl…
Prooxidative toxicity and selenoprotein suppression by cerivastatin in muscle cells
2012
Statins are the most widely used drugs for the treatment of hypercholesterolemia. In spite of their overall favorable safety profile, they do possess serious myotoxic potential, whose molecular origin has remained equivocal. Here, we demonstrate in cultivated myoblasts and skeletal muscle cells that cerivastatin at nanomolar concentrations interferes with selenoprotein synthesis and evokes a heightened vulnerability of the cells toward oxidative stressors. A correspondingly increased vulnerability was found with atorvastatin, albeit at higher concentrations than with cerivastatin. In selenium-saturated cells, cerivastatin caused a largely indiscriminate suppression of selenoprotein biosynth…
Statin-Induced Liver Injury Involves Cross-Talk between Cholesterol and Selenoprotein Biosynthetic Pathways
2009
Statins have become the mainstay of hypercholesterolemia treatment. Despite a seemingly clear rationale behind their use, the inhibition of HMG-CoA reductase, these compounds have been shown to elicit a variety of unanticipated and elusive effects and side effects in vivo. Among the most frequently noted side effects of statin treatment are elevations in liver enzymes. Here, we report our finding that atorvastatin, cerivastatin, and lovastatin at clinically common concentrations induce a selective, differential loss of selenoprotein expression in cultured human HepG2 hepatocytes. The primarily affected selenoprotein was glutathione peroxidase (GPx), whose biosynthesis, steady-state expressi…
Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.
2020
Abstract Objectives The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. Methods Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. The k e of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h−1. K a and V d parameters were taken from literature. Data from 128 subjects were divided into two groups (i.e., wild-types and carriers) and statistical analyses of PK parameters were performed by unpaired t-tests. Results In the carrier group (n=6…
How registers could enhance knowledge and characterization of genetic dyslipidaemias: The experience of the LIPIGEN in Italy and of other networks fo…
2020
Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism, still underdiagnosed and undertreated in the general population. Pathology registers could play a crucial role in the creation of a comprehensive and integrated global approach to cover all aspects of this disease. Systematic data collection of patients affected by FH has increased dramatically worldwide in the past few years. Moreover, results from registers already established for the longest time showed their potentialities in the implementation of the knowledge of FH, comparing country-specific approaches and providing real-world data about identification, management and treatment of FH individuals in t…
Increase by NO synthase inhibitors of acetylcholine release from guinea-pig myenteric plexus
1994
The effects of nitric oxide (NO) synthase inhibitors on the electrically evoked release of [3H]acetylcholine were studied in guinea-pig myenteric plexus preparations preincubated with [3H]choline. NG-monomethyl-L-arginine (EC50 5.3 mumol l-1) and NG-nitro-L-arginine (EC50 1.3 mumol l-1) concentration-dependently increased the evoked release of [3H]acetylcholine without affecting the basal outflow. The facilitatory effect of NG-mono-methyl-L-arginine was prevented by L-arginine but not by D-arginine. The results suggest that endogenous NO inhibits the depolarisation-evoked release of acetylcholine.
Head-to-head comparison of statins versus fibrates in reducing plasma fibrinogen concentrations: A systematic review and meta-analysis
2015
Several studies suggest differences between fibrates and statins in lowering plasma fibrinogen (Fib) concentrations, but the evidence is not definitive. Therefore, the aim of this meta-analysis of head-to-head randomized trials was to compare the efficacy of statins and fibrates on plasma Fib concentrations.The literature search included Medline, Scopus, and Web of Science up to February 1st, 2015, to identify head-to-head comparative randomized trials investigating the efficacy of fibrates vs statins on plasma Fib concentrations.In total 22 trials with 2762 participants were included to the meta-analysis. Random-effect meta-analysis suggested a significantly greater effect of fibrates vs s…
The role of statins in preventing the progression of congestive heart failure in patients with metabolic syndrome.
2008
Heart Failure (CHF) is a very important public health problem in the world and certainly one of the most common debilitating diseases and cause of mortality. Current knowledge underlines that incidence rates are also influenced by the coexisting pathologic conditions that accelerate the development of disease or increase its severity. Important scientific evidence is emerging to demonstrate a strong correlation between HF and the metabolic syndrome (MetS). Hypolipemia- inducing medication offers the opportunity to discuss the possible existence of pharmacological substances that in addition to their specific targets have several demonstrated pleiotropic effects that could be beneficial in H…
Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C
2011
Summary. Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All p…
Selenoprotein synthesis and side-effects of statins.
2004
Statins are possibly the most effective drugs for the prevention and treatment of hypercholesterolaemia and coronary heart disease. They are generally well tolerated, however, they do cause some unusual side-effects with potentially severe consequences, most prominently myopathy or rhabdomyolysis and polyneuropathy. We noted that the pattern of side-effects associated with statins resembles the pathology of selenium deficiency, and postulated that the mechanism lay in a well established, but often overlooked, biochemical pathway--the isopentenylation of selenocysteine-tRNA([Ser]Sec). A negative effect of statins on selenoprotein synthesis does seem to explain many of the enigmatic effects a…