Comparison of human hepatoma HepaRG cells with human and rat hepatocytes in uptake transport assays in order to predict drug induced hepatotoxicity

Human hepatocytes are the gold standard for toxicological studies but they have several drawbacks, like scarce availability, high inter-individual variability, a short lifetime, which limits their applicability. The aim of our investigations was to determine, whether HepaRG cells could replace human hepatocytes in uptake experiments for toxicity studies. HepaRG is a hepatoma cell line with most hepatic functions, including a considerable expression of uptake transporters in contrast to other hepatic immortalized cell lines. We compared the effect of cholestatic drugs (bosentan, cyclosporinA, troglitazone,) and bromosulfophthalein on the uptake of taurocholate and estrone-3-sulfate in human and rat hepatocytes and HepaRG cells. The substrate uptake was significantly slower in HepaRG cells than in human hepatocytes, still, in the presence of drugs we observed a concentration dependent decrease in uptake. In all cell types, the culture time had a significant impact not only on the uptake process but on the inhibitory effect of drugs too. The most significant drug effect was measured at 4 h after seeding. Our report is among the first concerning interactions of the uptake transporters in the HepaRG, at the functional level. Results of the present study clearly show that concerning the inhibition of taurocholate uptake by cholestatic drugs, HepaRG cells are closer to human hepatocytes than rat hepatocytes. In conclusion, we demonstrated that HepaRG cells provide a suitable tool for hepatic uptake studies

Long-term response of understorey cover, basal area and diversity to stand density in a mixed oak forest on the Síkfőkút plot in Hungary

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The effects of detritus inputs on soil organic matter content and carbon-dioxide emission in a Central European deciduous forest.

A major objective of our research was to survey s oil biological activity and organic matter content reduction in a Central European oak forest during treatments of various detritus inputs within the Síkf ő kút DIRT ( Detritus Input and Removal Treatments ) Project. Beside the control, three detritus removal and two detritus duplication treatments wer e applied. Our examinations have proven that soil organic matter content declined relatively fast in detritus removal treatments. The reduction was especially remarkable in root detritus removal trea tments, where – due to the lack of transpiration – soils were moister during the whole year than in the othe r treatments. The higher moisture content, despite of the reduction of detritus input, produced an intens e soil respiration. This can be explained by the fa ct that decomposing organisms have increased the use of soi l organic matter. Detritus input reduction had a significantly greater effect on soil respiration an d organic matter content than detritus input duplic ation of the same extent. The latter did not cause any si gnificant change compared to the control

The Effects of Detritus Input on Soil Organic Matter Content and Carbon Dioxide Emission in a Central European Deciduous Forest

A major objective of our research was to survey soil biological activity and organic mattercontent reduction in a Central European oak forest during treatments of various detritus inputs within theSíkfkút DIRT (Detritus Input and Removal Treatments) Project. Beside the control, three detritusremoval and two detritus duplication treatments were applied. Our examinations have proven that soilorganic matter content declined relatively fast in detritus removal treatments. The reduction wasespecially remarkable in root detritus removal treatments, where – due to the lack of transpiration – soilswere moister during the whole year than in the other treatments. The higher moisture content, despite ofthe reduction of detritus input, produced an intense soil respiration. This can be explained by the fact thatdecomposing organisms have increased the use of soil organic matter. Detritus input reduction had asignificantly greater effect on soil respiration and organic matter content than detritus input duplicationof the same extent. The latter did not cause any significant change compared to the control

Effects of Climate Change on Litter Production in a Quercetum petraeae-cerris Forest in Hungary

Climate change is a global problem. During the last century the increase of annual averagetemperature was 0.68°C, while the decrease of annual average of precipitation was 83 mm in Hungary.According to the long term meteorological data of Síkfkút forest ILTER site the annual averagetemperature increased while average of yearly precipitation decreased, the forest climate becamewarmer and dryer. These processes could considerably contribute to forest decline, not only in theQuercetum petraeae-cerris stand of Síkfkút, but everywhere in the country. Species composition andstructure of the forest have changed considerably, as 68% of sessile oak (Quercus petraea) and 16% ofTurkey oak (Quercus cerris) have died. Forest decline resulted in the breaking up of the formerlyclosed canopy, and consequently, in the formation of gaps in the forest. In the gaps, a secondary canopy developed with tree species of less forestry value. As a consequence, mass regeneration of field maple (Acer campestre) appeard in the gaps. The formation of gaps accelerated the warming and aridity of forests. In the article we answer the following question: how did climatic change and changing forest structure influence the leaf-litter production in the last four decades