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Oxidative Pathway (oxidative + pathway)
Selected AbstractsThe molecular mechanism underlying the reduction in abdominal fat accumulation by licorice flavonoid oil in high fat diet-induced obese ratsANIMAL SCIENCE JOURNAL, Issue 5 2009Kazuhisa HONDA ABSTRACT Licorice (Glycyrrhiza glabra) has been widely used in traditional medicines, and its flavonoid oil (LFO) decreases abdominal adipose tissue weight in mammals. In the present study, we investigated the molecular mechanisms underlying the decrease in abdominal adipose tissue weight by LFO. LFO significantly decreased the mRNA levels of rate-limiting enzymes in the hepatic fatty acid synthetic pathway, whereas LFO significantly increased the mRNA levels of a rate-limiting enzyme in the hepatic fatty acid oxidative pathway. LFO significantly decreased the mRNA levels of sterol regulatory element-binding protein-1c (SREBP-1c) (a transcription factor that promotes hepatic fatty acid synthesis), whereas the mRNA levels of peroxisome proliferator-activated receptor-, (PPAR-,) (a transcription factor that promotes hepatic fatty acid oxidation) was significantly increased. All our findings suggest that the decrease in abdominal adipose tissue weight by LFO is mediated by the transcriptional regulation of SREBP-1c and PPAR-, in the liver. Thus, we infer that the natural ingredient LFO is a promising candidate for use as a feed additive to reduce abdominal fat accumulation in domestic animals. [source] Ferrocene-bridging dinuclear cyclen copper(II) complexes as high efficient artificial nucleases: design, synthesis and interaction with DNAAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 5 2008Kun Li Abstract Two novel cyclen copper(II) complexes bridged by ferrocene were designed and synthesized. Both of these complexes exhibited excellent cleavage ability towards plasmid DNA via an oxidative pathway without the presence of any additives. Cyclic voltammetry was used to investigate the electrochemistry characters of the interaction between the complexes and DNA. Agarose gel electrophoresis was carried out to study the DNA restriction ability of these complexes, and the results indicated that the complexes showed higher cleavage efficiency via an oxidative pathway without the presence of any additives. The mechanism of DNA cleavage catalyzed by these complexes was examined by the addition of various scavengers, and the results showed that singlet oxygen and hydroxyl radical might be responsible for the cleavage process. Copyright © 2008 John Wiley & Sons, Ltd. [source] Oxidation of an Oligonucleotide-Bound CeIII/Multiphosphonate Complex for Site-Selective DNA ScissionCHEMISTRY - A EUROPEAN JOURNAL, Issue 3 2010Tuomas Lönnberg Dr. Abstract Oligodeoxyribonucleotide conjugates of ethylenediamine- N,N,N,,N,-tetrakis(methylenephosphonic acid) (EDTP) have been used to place a CeIII/EDTP complex in close proximity to predetermined phosphodiester linkages of a complementary target oligonucleotide. In the presence of atmospheric oxygen, the CeIII is oxidized into CeIV which, in turn, efficiently cleaves the target phosphodiester linkage. No cleavage occurs at the other single-stranded regions, which suggests that the catalytic Ce species is strictly localized next to the target phosphodiester linkage. No decrease in the reaction rate is observed upon introduction of scavengers for hydroxyl radicals (such as DMSO or MeOH) or singlet oxygen (such as NaN3) to the system; this indicates that the reaction proceeds via a hydrolytic pathway. Any significant contribution by an oxidative pathway is further ruled out by the observation that nucleosides remain intact after incubation with CeIV/EDTP complex for extended periods. [source] KYNURENINE PATHWAY METABOLISM IN PATIENTS WITH OSTEOPOROSIS AFTER 2 YEARS OF DRUG TREATMENTCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2006Caroline M Forrest ABSTRACT 1Metabolism of tryptophan along the oxidative pathway via kynurenine results in the production of quinolinic acid and kynurenic acid, which can act on glutamate receptors in peripheral tissues. We have now measured the concentrations of kynurenine pathway metabolites in the plasma of patients with osteoporosis before treatment with drugs, throughout and after 2 years of treatment with the drugs raloxifene or etidronate. Oxidative stress was assessed by measuring levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Kynurenines were analysed by HPLC. Bone density was measured using dual-energy X-ray absorptiometry scans. 2Patients with osteoporosis showed significantly lower baseline levels of 3-hydroxyanthranilic acid compared with healthy controls, but significantly higher levels of anthranilic acid and lipid peroxidation products. After 2 years treatment with etidronate and calcium, we observed significant therapeutic responses quantified by bone densitometric scanning. Significant improvements were not seen in patients treated with raloxifene. 3In parallel, the levels of 3-hydroxyanthranilic acid, anthranilic acid and lipid peroxidation products were restored to control values by both drug treatments studied and tryptophan levels were increased significantly compared with baseline values. 4The results suggest that tryptophan metabolism is altered in osteoporosis in a manner that could contribute to the oxidative stress and, thus, to progress of the disease. The oxidative metabolism of tryptophan (the kynurenine pathway) could represent a novel target for the development of new drugs for the treatment of osteoporosis. In addition, we noted that etidronate is a more effective drug than raloxifene, but that the simultaneous use of non-steroidal anti-inflammatory drugs may reduce the efficacy of etidronate. [source] Production of delta-endotoxin by Bacillus thuringiensis subsp kurstaki and overcoming of catabolite repression by using highly concentrated gruel and fish meal media in 2- and 20-dm3 fermentersJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 8 2002Nabil Zouari Abstract Delta-endotoxin production by a strain of Bacillus thuringiensis subsp kurstaki exhibiting larvicidal toxicity towards lepidoptera was investigated in 2- and 20-dm3 fermenters, using gruel- and fish meal-based media. The results show clearly that in such complex media, aeration plays an important role in bioinsecticide production. Optimal aeration led to improvement of delta-endotoxin concentrations with decreases of final spore count and proteolytic activity. Moreover, in order to use high gruel concentrations, a fermenter configuration with an efficient aeration system should be used. In a 20-dm3 Biolafite fermenter, 59,g,dm,3 or 75,g,dm,3 gruel was used to produce bioinsecticides with a significant reduction of carbon catabolite repression of delta-endotoxin synthesis. This result is very interesting in order to produce high final delta-endotoxin concentrations in the culture broth. It was also concluded, by considering the key role of oxidative pathways in delta-endotoxin synthesis, that oxygen supply must be adequate for bioinsecticide production at high substrate concentrations. Moreover, the role of sodium chloride in improving delta-endotoxin production is dependent not only on protease synthesis and its effect on crystal stability, but also on the aeration level of the production medium. © 2002 Society of Chemical Industry [source] Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 aloneBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010Juha Grönlund WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Oxycodone is an opioid analgesic that is metabolized mainly in the liver by cytochrome P450 (CYP) 2D6 and 3A4 enzymes. , So far, the effects of CYP2D6 or CYP3A4 inhibitors on the pharmacokinetics of oxycodone in humans have not been systematically studied. WHAT THIS STUDY ADDS , Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone. , When both of CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. AIM The aim of this study was to find out whether the inhibition of cytochrome P450 2D6 (CYP2D6) with paroxetine or concomitant inhibition of CYP2D6 and CYP3A4 with paroxetine and itraconazole, altered the pharmacokinetics and pharmacological response of orally administered oxycodone. METHODS A randomized placebo-controlled cross-over study design with three phases was used. Eleven healthy subjects ingested 10 mg of oral immediate release oxycodone on the fourth day of pre-treatment with either placebo, paroxetine (20 mg once daily) or paroxetine (20 mg once daily) and itraconazole (200 mg once daily) for 5 days. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h, and pharmacological (analgesic and behavioural) effects were evaluated. RESULTS Paroxetine alone reduced the area under concentration,time curve (AUC(0,0,48 h)) of the CYP2D6 dependent metabolite oxymorphone by 44% (P < 0.05), but had no significant effects on the plasma concentrations of oxycodone or its pharmacological effects when compared with the placebo phase. When both oxidative pathways of the metabolism of oxycodone were inhibited with paroxetine and itraconazole, the mean AUC(0,,) of oxycodone increased by 2.9-fold (P < 0.001), and its Cmax by 1.8-fold (P < 0.001). Visual analogue scores for subjective drug effects, drowsiness and deterioration of performance were slightly increased (P < 0.05) after paroxetine + itraconazole pre-treatment when compared with placebo. CONCLUSIONS Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone if the function of the CYP3A4 pathway is normal. When both CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. [source] | |||||||||||||