Chemiluminescence response induced by mesenteric ischaemia/reperfusion: effect of antioxidative compounds ex vivo

Ischaemia and reperfusion (I/R) play an important role in human pathophysiology as they occur in many clinical conditions and are associated with high morbidity and mortality. Interruption of blood supply rapidly damages metabolically active tissues. Restoration of blood flow after a period of ischaemia may further worsen cell injury due to an increased formation of free radicals. The aim of our work was to assess macroscopically the extent of intestinal pathological changes caused by mesenteric I/R, and to study free radical production by luminol enhanced chemiluminescence (CL) of ileal samples. In further experiments, the antioxidative activity of the drugs tested was evaluated spectrophotometrically by the use of the DPPH radical. We studied the potential protective ex vivo effect of the plant origin compound arbutin as well as of the pyridoindole stobadine and its derivative SMe1EC2. I/R induced pronounced haemorrhagic intestinal injury accompanied by increase of myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGA) activity. Compared to sham operated (control) rats, there was only a slight increase of CL response after I/R, probably in association with neutrophil increase, indicated by enhanced MPO activity. All compounds significantly reduced the peak values of CL responses of the ileal samples ex vivo, thus reducing the I/R induced increase of free radical production. The antioxidants studied showed a similar inhibitory effect on the CL response influenced by mesenteric I/R. If proved in vivo, these compounds would represent potentially useful therapeutic antioxidants

Protection of the vascular endothelium in experimental situations

One of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) and aorta, as well as by increased endothelaemia. Changes in endothelium-dependent relaxation of SMA were induced by injury of the nitric oxide radical (·NO)-signalling pathway since the endothelium-derived hyperpolarising factor (EDHF)-component of relaxation was not impaired by diabetes. The endothelial dysfunction was accompanied by decreased ·NO bioavailabity as a consequence of reduced activity of eNOS rather than its reduced expression. The results obtained using the chemiluminiscence method (CL) argue for increased oxidative stress and increased ROS production. The enzyme NAD(P)H-oxidase problably participates in ROS production in the later phases of diabetes. Oxidative stress was also connected with decreased levels of reduced glutathione (GSH) in the early phase of diabetes. After 10 weeks of diabetes, adaptational mechanisms probably took place because GSH levels were not changed compared to controls. Antioxidant properties of SMe1EC2 found in vitro were partly confirmed in vivo. Administration of SMe1EC2 protected endothelial function. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of ·NO in the aorta. Further studies with higher doses of SMe1EC2 may clarify the mechanism of its endothelium-protective effect in vivo

Metal-containing landfills as a source of antibiotic tolerance

To unveil the potential effect of metal presence to antibiotic tolerance proliferation, four sites of surface landfills containing tailings from metal processing in Slovakia (Hnusta, Hodrusa, Kosice) and Poland (Tarnowskie Gory) were investigated. Tolerance and multitolerance to selected metals (Cu, Ni, Pb, Fe, Zn, Cd) and antibiotics (ampicillin, tetracycline, chloramphenicol, and kanamycin) and interrelationships between them were evaluated. A low bacterial diversity (Shannon-Wiener index from 0.83 to 2.263) was detected in all sampling sites. Gram-positive bacteria, mostly belonging to the phylum Actinobacteria, dominated in three of the four sampling sites. The recorded percentages of tolerant bacterial isolates varied considerably for antibiotics and metals from 0 to 57% and 0.8 to 47%, respectively, among the sampling sites. Tolerances to chloramphenicol (45-57%) and kanamycin (32-45%) were found in three sites. Multitolerance to several metals and antibiotics in the range of 24 to 48% was recorded for three sites. A significant positive correlation (p < 0.05) for the co-occurrence of tolerance to each studied metal and at least one of the antibiotics was observed. Exposure time to the metal (landfill duration) was an important factor for the development of metal-as well as antibiotic-tolerant isolates. The results show that metal-contaminated sites represent a significant threat for human health not only for their toxic effects but also for their pressure to antibiotic tolerance spread in the environment.Web of Science1952art. no. 26