Effect of pomiferin administration on kidney ischaemia-reperfusion injury in rats

The aim of the study was to analyse protective effects of different doses of pomiferin in therapy of reperfusion injury. Rats were randomly divided into five groups (n=10). One group was intact. Three medicated groups and one placebo group were subjected to ischaemia and reperfusion of the left kidney. Pomiferin was administrated by single gastric gavage in 2 ml of 0.5% Avicel solution in doses of 5, 10 and 20 mg/kg. The placebo group was given only Avicel solution. On day 15, all the animals were exsanguinated and the reperfused kidneys were recovered. Selected biochemical markers were assessed in blood: antioxidative enzymes, total antioxidative capacity, malondialdehyde, creatinine, urea and uric acid. Creatinine, urea and total proteins were analysed in urine and 24-hour diuresis was recorded. The kidney tissue samples were used for histopathological examination

Human Polymorphonuclear Leukocytes: Effect of Chloroquine on Aggregation, Arachidonic Acid Liberation and Thromboxane B 2 Generation

Abstract. The effects of the antimalanal chug chloioqume (CQ) on aiachidonic acid (AA) hbeiation fiom tlnomboxane B 2 (TXB 2 ) foimation m, and aggiega tion of isolated human polymoiphonucleai (PMN) leukocytes stimulated with Nfoimyl methionyl leucyl phenyl alanine (FMLP) weie investigated CQ decieased aggiegation of stimulated PMN leukocytes howevei m contiast to AA hbeiation and TXB 2 foimation lowei concentiations weie moic effective than the highest one used This effect may be associated with an inciease in mtiacellulai pH repoited to be induced by highei CQ concentiations possibly counteiacting the inhibition of aggregation and/oi eliminating negative feed back contiol of aggiegation by lack of piostaglandins Key words: Human PMN leukocytes -Chloioqume -Aggiegation -Aiachi donic acid hbeiation -Tlnomboxane B 2 foimation The antimalanal and antnnflammatoiy chug chloioqume (CQ) was íepoited to inhibit phospholipid methylation, piotem kinase and calmodulm-dependent ki nases m human monocytes (Huist et al 1986) and the geneiation of ieactive oxy gen species m stimulated human PMN leukocytes (Huist et al 1987) Inhibition of blood platelet aggregation and histamine secretion fiom mast cells was sug gested to be due to the high affinity of CQ to the plasma cell membrane of these cells (Nosal et al 1991 Jančmova et al 1994 In both platelets and mast cells, CQ dose-dependentl} inhibited aiachidonic acid pathway at the phosphohpase A 2 Conespondence to lana Penvova Institute of Experimental Pharmacologv Slovak Academy of Sciences Dubiavska cesta 9 842 16 Bratislava Slovakia Fax +421 7 375 928 e-mail exfa|appQ)savba s

The role of redox imbalance in relation to immunological process in adjuvant arthritis

The model of adjuvant arthritis (AA) is well characterized concerning the immunological processes involved. However knowledge on the participation of redox imbalance in the progression of AA is scarce. The link between oxidative stress (OS) and immunological status in arthritis should be more precisely investigated. In our experiments, we focused on AA development in the time domain. AA was induced in rats by a single intradermal injection of Mycobacterium butyricum in incomplete Freund’s adjuvant. All experiments included healthy animals (HC) and arthritic animals not treated. We confirmed that the clinical parameters hind paw volume and body weight became significantly modified starting around day 14 after AA induction and this change was maintained until the end of the experiment (day 28). We obtained a good agreement of clinical parameters with parameters of OS. Measurements of plasmatic protein carbonyls revealed damage of proteins caused by OS. Progression of lipid peroxidation in AA was described by analysis of TBARS, HNE- /MDA-protein adducts and F2 isoprostane levels in plasma. Total antioxidant status analyzed in plasma was decreased significantly in both the acute (day 21) and the subchronic phase (day 28) of AA. Further we focused on evaluating CoQ9 plasmatic levels. The arthritic process increased significantly the level of CoQ9 in comparison to HC. Evidently, the arthritic process stimulates the synthesis of CoQ9 and its transport to plasma. In the model of AA, we observed already on experimental day 7 that AA was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as phorbol myristate acetate stimulated chemiluminescence. As the changes in neutrophils occur before the clinical parameter HPV starts to be increased, for further evaluation of neutrophil functionality we chose experimental day 7. The functionality of peripheral blood neutrophils in AA was described by phagocytosis, oxidative burst and metabolic activity. Both phagocytosis and oxidative burst were increased due to arthritis, and that despite the decreased metabolic activity. Analysis of OS in tissue showed changed GGT activity in spleen and joint homogenate accompanied by increased chemiluminescence. The OS parameters were in close relationship with time profiles of selected cytokines, chemokine MCP-1 and of C-reactive protein levels in plasma. Measurements of the immunoregulatory index in peripheral blood and lipoxygenase tissue activity (lung, liver) were also included. Our observations have evidenced the importance of pharmacological regulation of redox imbalance in arthritis. (VEGA 2/0090/08, COST B35, APVV-51-017905, APVV-21-055205