Our previous studies have shown that the combined administration of drugs elevating extracellular adenosine, i.e. dipyridamole (DP) and adenosine monophosphate (AMP), enhances murine hematopoiesis and potentiates the action of granulocyte colony-stimulating factor (G-CSF). In this study, colony-stimulating activity (CSA) of blood serum of mice treated with DP+AMP, G-CSF or all these drugs in combination, i.e. the ability of the sera to stimulate the growth of GM-CFC colonies, was assayed in vitro. Furthermore, the concentration of GM-CSF and IL-6 in the sera was determined. Administration of DP+AMP was found to enhance significantly serum CSA at all time intervals of serum sampling including 24 h after the last injection of the tested drugs. Additive effects of DP+AMP and G-CSF on serum CSA were noted at early intervals after administration of the drugs. Furthermore, IL-6 levels were significantly elevated in the sera of mice which were administered DP+AMP either alone or in combination with G-CSF. Our results show that the effects of DP+AMP are indirect, mediated through the induction of some cytokine(s) and/or growth factor(s) and that extracellular adenosine can act in cooperation with G-CSF. These findings contribute to the further elucidation of the role of adenosine in hematopoiesis.

• MeSH
• adenosin analogy a deriváty   imunologie   MeSH
• adenosinmonofosfát aplikace a dávkování   krev   MeSH
• dipyridamol aplikace a dávkování   krev   MeSH
• ELISA normy   využití   MeSH
• extracelulární prostor genetika   imunologie   účinky léků   MeSH
• faktor stimulující kolonie granulocytů izolace a purifikace   účinky léků   MeSH
• financování organizované využití   MeSH
• myši inbrední CBA krev   MeSH
• myši inbrední ICR krev   MeSH

We studied cadmium toxicity in murine hepatocytes in vitro. Cadmium effects on intracellular free Ca2+ concentration ([Ca2+]i) were assayed, using a laser scanning confocal microscope with a fluorescent probe, Fluo-3/AM. The results showed that administration of cadmium chloride (CdCl2, 5, 10, 25 µM) resulted in a dose-dependent decrease of hepatocyte viability and an elevated aspartate aminotransferase (AST) activity in the culture medium (p<0.05 for 25 µM CdCl2 vs. control). Significant increases of lactate dehydrogenase (LDH) activities in 10 and 25 µM CdC12-exposed groups were observed (p<0.05 and p<0.01, respectively). A greatly decreased albumin content and a more malondialdehyde (MDA) formation also occurred after CdC12 treatment. The Ca2+ concentrations in the culture medium of CdCl2-exposed hepatocytes were significantly decreased, while [Ca2+]i appeared to be significantly elevated (p<0.05 or p<0.01 vs. control). We found that in Ca2+-containing hydroxyethyl piperazine ethanesulfonic acid-buffered salt solution (HBSS) only, CdCl2 elicited [Ca2+]i increases, which comprised an initially slow ascent and a strong elevated phase. However, in Ca2+-containing HBSS with addition of 2-aminoethoxydiphenyl borane (2-APB), CdCl2 caused a mild [Ca2+]i elevation in the absence of an initial rise phase. Removal of extracellular Ca2+ showed that CdCl2 induced an initially slow [Ca2+]i rise alone without being followed by a markedly elevated phase, but in a Ca2+-free HBSS with addition of 2-APB, CdCl2 failed to elicit the [Ca2+]i elevation. These results suggest that abnormal Ca2+ homeostasis due to cadmium may be an important mechanism of the development of the toxic effect in murine hepatocytes. [Ca2+]i elevation in acutely cadmium-exposed hepatocytes is closely related to the extracellular Ca2+ entry and an excessive release of Ca2+ from intracellular stores.

• MeSH
• chlorid kademnatý škodlivé účinky   toxicita   MeSH
• finanční podpora výzkumu jako téma MeSH
• hepatocyty cytologie   chemie   účinky léků   MeSH
• homeostáza fyziologie   účinky léků   MeSH
• kadmium chemie   škodlivé účinky   toxicita   MeSH
• konfokální mikroskopie metody   využití   MeSH
• myši inbrední ICR anatomie a histologie   krev   MeSH
• poruchy metabolismu vápníku etiologie   komplikace   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

• MeSH
• B-lymfocyty cytologie   fyziologie   imunologie   MeSH
• buňky NK fyziologie   imunologie   MeSH
• CD4-pozitivní T-lymfocyty cytologie   fyziologie   imunologie   MeSH
• CD8-pozitivní T-lymfocyty fyziologie   imunologie   MeSH
• Escherichia coli genetika   imunologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• myši inbrední ICR fyziologie   imunologie   krev   MeSH
• receptory TNF fyziologie   imunologie   krev   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH