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 aminotransfe rase (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 CdCl2-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 CdCl2 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 [Ca 2+] 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., S. S. Wang, L. Chen, S. K. Xia., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to measure expression levels of microRNAs (miRNAs) (miRNA-1, -15b and -21) in the rat myocardium after a single dose of ionizing radiation (6-7 Gy/min, total 25 Gy). The rats were treated with selected drugs (Atorvastatin, acetylsalicylic acid (ASA), Tadalafil, Enbrel) for six weeks after irradiation. MiRNAs levels were measured by RT-qPCR. Irradiation down-regulated miRNA-1 in irradiated hearts. In Tadalafil- and Atorvastatin-treated groups, miRNA-1 expression levels were further decreased compared with irradiated controls. However, Enbrel increased miRNA-1 level in irradiated hearts similarly to that in non-irradiated untreated group. Increase of miRNA-15b is pro-apoptotic in relationship with ischemia. Irradiation caused down-regulation of miRNA-15b. Administration of ASA in the irradiated group resulted in the increase of miRNA-15b expression compared to non-treated controls without irradiation. After Enbrel administration, miRNA-15b levels were overexpressed compared to non-treated normal group. MiRNA-21 belongs to the most markedly up-regulated miRNAs in response to cardiogenic stress. MiRNA-21 was increased nearly 2-fold compared to non-treated hearts whereas Tadalafil reduced miRNA-21 levels (about 40 %). Our study suggests that Enbrel and Tadalafil changed miRNAs expression values of the irradiated rats to the values of nonirradiated controls, thus they might be helpful in mitigation of radiation-induced toxicity., B. Kura, C. Yin, K. Frimmel, J. Krizak, L. Okruhlicova, R. C. Kukreja, J. Slezak., and Obsahuje bibliografii
This work aimed to study the effects of commercial doses of the fungicide, Mancozeb, on the photosynthetic apparatus of lettuce young leaves (YL) and expanded leaves (EL). Seven days after Mancozeb application, chlorophyll a fluorescence, pigment contents, lipid peroxidation, and proline content were evaluated. Independently of leaf age, Mancozeb treatment reduced the efficiency of photosystem II photochemistry, increased the nonphotochemical quenching and proline content, decreased pigment contents, and induced lipid peroxidation. Moreover, EL showed a more stable photosynthetic apparatus, less prone to oxidative damages compared with YL. The parameters measured proved to be good markers for the rapid and preliminary diagnosis of fungicide toxicity., M. C. Dias, P. Figueiredo, I. F. Duarte, A. M. Gil, C. Santos., and Obsahuje bibliografii
Agroclavine is a natural, clavine type of ergot alkaloid with D1 dopamine and ?-adrenoceptor agonistic properties. We showed previously that in vitro agroclavine enhances natural killer (NK) cell activity, increases interleukin-2 and interferon-gamma production and prolongs the survival time of tumor-bearing mice. The aim of this study was 1) to test the effect of agroclavine on NK activity in vivo, and 2) to assess the potential toxicity of high doses of agroclavine on cardiac and liver functions using creatine kinase MB (CKMB) and alanine aminotransferase (ALT) as biochemical markers in normal and stressed animals. The effect of stress was studied because we examined promising anticancer properties of agroclavine and malignant diseases are supposed to be a potent stressful event for patients. In our experiments 3-month-old male rats of the Wistar-Kyoto strain were used. Agroclavine was injected intraperitoneally (0.5 mg/kg or 0.05 mg/kg) 30 min before stress (four hours' restraint and immersion in 23 °C water). The animals were killed 30 min after stress, blood was collected and the spleen was removed. Non-stressed animals treated with agroclavine were killed 5 h after the drug administration. The results confirmed our previous in vitro results and showed that also in vivo agroclavine increases NK cell activity under non-stress conditions. Agroclavine only slightly increased CKMB and had no influence on ALT in non-stressed animals. These promising results are limited by the fact that agroclavine (0.5 mg/kg) diminished NK cell activity and significantly increased ALT and CKMB under stress conditions., M. Starec, A. Fišerová, J. Rosina, J. Málek, M. Kršiak., and Obsahuje bibliografii