Antioxidant and prooxidant action of nitric oxide donors and metabolites

Different nitric oxide donors and metabolites proved to have similar effects on the peroxidation in rat myocardium homogenate. PAPA-NONOate (synthetic nitric oxide donor), S-nitrosoglutathione, nitrite, and nitroxyl anion caused dose-dependent inhibition of the formation of malonic dialdehyde, a secondary product of lipid peroxidation. Dextran-bound dinitrosyl iron complexes and PAPA-NONOate were the most efficient inhibitors of lipid peroxidation. S-Nitrosoglutathione also inhibited the decline in coenzymes Q₉ and Q₁₀. Low-molecular-weight dinitrosyl iron complexes with cysteine accelerated lipid peroxidation, which could be caused by the release of iron ions upon their destruction. The antioxidant effect of nitric oxide donors appears to be due to the reduction of hemoprotein ferryl forms and the reaction of nitric oxide with lipid radicals.     

Molecular Hazard Identification of Non-O157 Shiga Toxin-Producing Escherichia coli (STEC)

The complexity regarding Shiga toxin-producing Escherichia coli (STEC) in food safety enforcement as well as clinical care primarily relates to the current inability of an accurate risk assessment of individual strains due to the large variety in serotype and genetic content associated with (severe) disease. In order to classify the clinical and/or epidemic potential of a STEC isolate at an early stage it is crucial to identify virulence characteristics of putative pathogens from genomic information, which is referred to as ‘predictive hazard identification’. This study aimed at identifying associations between virulence factors, phylogenetic groups, isolation sources and seropathotypes. Most non-O157 STEC in the Netherlands belong to phylogroup B1 and are characterized by the presence of ehxA, iha and stx ₂, but absence of eae. The large variability in the number of virulence factors present among serogroups and seropathotypes demonstrated that this was merely indicative for the virulence potential. While all the virulence gene associations have been worked out, it appeared that there is no specific pattern that would unambiguously enable hazard identification for an STEC strain. However, the strong correlations between virulence factors indicate that these arrays are not a random collection but are rather specific sets. Especially the presence of eae was strongly correlated to the presence of many of the other virulence genes, including all non-LEE encoded effectors. Different stx-subtypes were associated with different virulence profiles. The factors ehxA and ureC were significantly associated with HUS-associated strains (HAS) and not correlated to the presence of eae. This indicates their candidacy as important pathogenicity markers next to eae and stx _2a.     

见血封喉乳汁脂溶性成分及其抗氧化活性研究

首次采用气相色谱.质谱联用技术(GC-MS)对见血封喉(Antiaris toxicaria(Pers.)Lesch.)乳汁的脂溶性成分进行了分析,共鉴定了27个化学成分,占其总量的91.7%.用清除DPPH自由基能力的方法测定了见血封喉乳汁脂溶性部位的抗氧化活性,结果显示出一定的抗氧化活性,SC50值为500μg ml-1.     

Changes in antioxidant status of myocardium during oxidative stress under the influence of coenzyme Q<Subscript>10</Subscript>

Changes in myocardium were studied during oxidative stress induced by infusion of hydrogen peroxide in the coronary vessels of isolated rat heart. Moderate concentrations of H2O2 increased the heart rate but decreased the contractile force, whereas higher concentrations of H2O2 decreased both parameters and increased the end diastolic pressure. The effect of H2O2 was stable, cumulative, and was associated with disturbance in respiration of mitochondria, increased production of ROS in them, and decrease in activities of antioxidant enzymes in the myocardium. Changes in the antioxidant status of the myocardium induced by long-term addition of coenzyme Q(10) into food was accompanied by decrease in the negative inotropic effect of H2O2, whereas the levels of superoxide dismutase and glutathione peroxidase after oxidative stress were virtually unchanged. The activities of these enzymes displayed a high positive correlation with the cardiac function. The findings suggest that coenzyme Q(10) should increase resistance of the myocardium to oxidative stress not only by a direct antioxidant mechanism but also indirectly, due to increased protection of antioxidant enzymes.     

Antioxidant and prooxidant action of nitric oxide donors and metabolites

It has been shown that various nitric oxide donors and metabolites have similar effects on lipid peroxidation in rat myocardium homogenate. The formation of malondialdehyde, a secondary product of lipid peroxidation, was inhibited in a dose-dependent manner by PAPA/NONO (a synthetic nitric oxide donor), S-nitrosoglutathione, nitrite, and nitroxyl anion. The inhibition of lipid peroxidation was provided most efficiently by the administration of dinitrosyl-iron complexes with dextran and PAPA/NONO. S-nitrosoglutathione also inhibited the destruction of coenzymes Q9 and Q10 during free radical oxidation of myocardium homogenate. Low-molecular-weight dinitrosyl iron complexes with cysteine also promoted lipid peroxidation, which is probably due to iron release during the destruction dinitrosyl iron complexes. It is likely that the antioxidant action of nitric oxide derivatives is related to the reduction of ferry forms of hemoproteins and interaction of nitric oxide with lipid radicals.     

Redox status and pharmacokinetics of coenzyme Q10 in rat plasma after its single intravenous administration

The pharmacokinetics of the total pool of coenzyme Q₁₀ (CoQ₁₀), its oxidized (ubiquinone) and reduced (ubiquinol, CoQ₁₀H₂) forms have been investigated in rats plasma during 48 h after a single intravenous injection of a solution of solubilized CoQ₁₀ (10 mg/kg) to rats. Plasma levels of CoQ₁₀ were determined by HPLC with spectrophotometric and coulometric detection. In plasma samples taken during the first minutes after the CoQ₁₀ intravenous injection, the total pool of coenzyme Q₁₀ and proportion of CoQ₁₀H₂ remained unchanged during two weeks of storage at ?20°C. The kinetic curve of the total pool of coenzyme Q₁₀ corresponds to a one-compartment model (R ₂ = 0.9932), while the corresponding curve of its oxidized form fits to the two-compartment model. During the first minutes after the injection a significant portion of plasma ubiquinone undergoes reduction, and after 7 h the concentration of ubiquinol predominates. The decrease in total plasma coenzyme Q₁₀ content was accompanied by the gradual increase in plasma ubiquinol, which represented about 90% of total plasma CoQ₁₀ by the end of the first day. The results of this study demonstrate the ability of the organism to transform high concentrations of the oxidized form of CoQ₁₀ into the effective antioxidant (reduced) form and justify prospects of the development of parenteral dosage forms of CoQ₁₀ for the use in the treatment of acute pathological conditions.     

Bioavailability of dalargin and its metabolism during intranasal administration to rats

Bioavailability and metabolism of a peptide drug Dalargin with a chemical structure Tyr-D-Ala-Gly-Phe-Leu-Arg have been examined. Dalargin is applied for the treatment of gastric and duodenal ulcers. Bioavailability was estimated following intramuscular (i/m) and intranasal (i/n) routes of administration of 3H-dalargin in anesthetized dogs. The highest dalargin concentration was achieved about 10 min after i/m and i/n administration. Absolute dalargin bioavailability was 15% and 8%, while its elimination half-life was 23.2 min and 21.3 min, respectively. Tyrosine, N-terminated tetra- and pentapeptides were the main metabolites detected in the blood. The intranasal route of dalargin administration is concluded to be possible in the clinical practice.