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EN
The aim of this study was to evaluate the therapeutic potential of oxidative stress (OS) reduction by using pyridoindole (PI) antioxidants in adjuvant arthritis (AA). The substances tested were stobadine dipalmitate (STB) and SMe1. AA was used as animal model. The experiments included healthy animals, control arthritic animals and arthritic animals with administration of PI in the oral daily dose of 15 mg/kg b.m during 28 experimental days. The rats were sacrificed on day 28. Clinical and biochemical parameters were determined. The effect of PI administration was evaluated on the basis of the following parameters: (a) arthritis (volume of hind paws - HPW, change of animal body mass - CBM), (b) OS (chemiluminescence of whole blood - CWB, levels of thiobarbituric acid reacting substance - TBARS and of HNE- and MDA-protein adducts in plasma and activity of γ-glutamyltransferase (GGT) in hind paw joint homogenates). The PI studied significantly increased the CBM of animals and corrected the HPW. STB also significantly decreased the activity of GGT in joint homogenates. SMe1 was more effective in decreasing plasmatic TBARS levels, but STB was more effective in reducing plasmatic HNE- and MDA-protein adducts. The assay for HNE- and MDA-adducts in plasma as a function of time was applied for the first time in AA. STB markedly decreased spontaneous and PMA-stimulated CWB and reduced neutrophil count. In summary, STB was more effective than SMe1 in reducing OS in AA. Our results showed that the reduction of OS in arthritis also corrected the clinical manifestations of the disease.
Kosmos
|
2017
|
vol. 66
|
issue 4
623-634
PL
Neutrofilowe sieci zewnątrzkomórkowe (NET) to niedawno odkryty mechanizm, dzięki któremu neutrofile mogą skutecznie walczyć z patogenami. W wyniku aktywacji neutrofile wyrzucają zdekondensowany DNA, połączony z histonami i białkami pochodzącymi z ziarnistości. Te przestrzenne struktury mogą wyłapywać, ograniczać rozprzestrzenianie się, a w niektórych przypadkach zabijać patogeny. Pomimo korzystnych efektów, NET są także odpowiedzialne za patogenezę różnych chorób autoimmunizacyjnych, takich jak reumatoidalne zapalenie stawów, łuszczyca czy toczeń rumieniowaty układowy, a także przyczyniają się do uszkodzeń narządów w trakcie sepsy. Jak dotąd niewiele wiadomo o tym jak NET są usuwane z naczyń krwionośnych i narządów oraz przez które komórki. Istniejące, nieliczne doniesienia wskazują na udział makrofagów w usuwaniu NET, jednakże wyniki te pochodzą tylko z eksperymentów in vitro. Otwartym pozostaje zatem pytanie o mechanizmy tego procesu w skomplikowanym środowisku żywego organizmu. W związku z patologicznym aspektem tworzenia NET, ważnym będzie opracowanie skutecznego środka farmakologicznego zdolnego do usuwania tych struktur.
EN
Neutrophil extracellular traps (NET) represent a recently discovered mechanism by which neutrophils can efficiently fight pathogens. Upon activation, neutrophils release decondensed extracellular DNA decorated with histones and granular proteins. These three-dimensional structures can trap pathogens, limit their spread and sometimes kill them. Despite their beneficial effects, NETs are also involved in pathogenesis of various autoimmune diseases, such as rheumatoid arthritis, psoriasis or systemic lupus erythematosus, and also contribute to organ damage during sepsis. So far, little is known on how NETs are removed from vasculature and tissues, and by which cells. Limited available studies indicate that macrophages might remove NETs, but these results were obtained in vitro. Thus it remains unknown how this process occurs in a complex milieu of the body. Due to the pathological aspect of NET formation, a challenge for the near future will be development of pharmacological agents capable of NET removal.
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