Decrease in intracellular Zn²⁺ level by propranolol : A model experiment using rat thymocytes

Propranolol is a representative β-blocker used for the treatment of cardiovascular diseases. Because the use of propranolol expands for some clinical purposes that are not related to its β-blocking action, it is necessary to further examine cellular actions of propranolol. We revealed that propranolol decreased the intracellular Zn2+ level in rat thymocytes by the use of cytometric technique with FluoZin-3, a fluorescent indicator of intracellular Zn2+. Propranolol decreased the influx of extracellular Zn2+. However, the agent decreased the intracellular Zn2+ level even in the presence of DTPA, a chelator of extracellular Zn2+. Thus, the decrease in intracellular Zn2+ level by propranolol was not due to the decrease in Zn2+ influx by propranolol. Propranolol increased the cellular content of nonprotein thiol that was estimated by the use of 5-chloromethylfluorescein fluorescence, an indicator for non-proteinous thiol. Since non-proteinous thiols can make a complex with Zn2+, propranolol may increase the cellular content of nonprotein thiol, resulting in the decrease in intracellular Zn2+ level. Since the concentrations of propranolol to affect both intracellular Zn2+ level and cellular content of nonprotein thiol are higher than those reported under clinical conditions, it is difficult to emphasize clinical implications from present results

Potential Use of Biological Proteins for Liver Failure Therapy

Biological proteins have unlimited potential for use as pharmaceutical products due to their various biological activities, which include non-toxicity, biocompatibility, and biodegradability. Recent scientific advances allow for the development of novel innovative protein-based products that draw on the quality of their innate biological activities. Some of them hold promising potential for novel therapeutic agents/devices for addressing hepatic diseases such as hepatitis, fibrosis, and hepatocarcinomas. This review attempts to provide an overview of the development of protein-based products that take advantage of their biological activity for medication, and discusses possibilities for the therapeutic potential of protein-based products produced through different approaches to specifically target the liver (or hepatic cells: hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells, and Kupffer cells) in the treatment of hepatic diseases

An evaluation of novel biological activity in a crude extract from <i>Hemerocallis fulva</i> L. var.<i> sempervirens</i> M. Hotta

<div><p><i>Hemerocallis fulva</i> L. var.<i> sempervirens</i> M. Hotta (<i>kwanso</i>) represents an exceptional resource for identifying and developing new phytomedicines for the treatment and prevention of disease. The aim of this study was to conduct a detailed investigation of the biological activities of <i>kwanso</i>. Our study resulted in four major findings. First, <i>kwanso</i> scavenges hydroxyl radicals generated by H₂O₂/UV light system <i>in vitro</i> in a dose-dependent manner. Second, hepatic glutathione levels were significantly increased when <i>kwanso</i> was orally administered to mice. Third, the oral administration of <i>kwanso</i> to mice showed a tendency to suppress hepatic injury induced by acetaminophen. Finally, <i>kwanso</i> slightly inhibited cytochrome P450 3A activity. These results provide useful evidence in support of the development of <i>kwanso</i> as a candidate raw material for the treatment and prevention of disease.</p></div

Effects of Ole on the binding of DNSA (4–24μM) to HSA (40μM) in the presence of ibuprofen at pH 6.5 and 25°C.

<p>The concentration ratio of Ole to HSA are 0 (A), 1 (B) and 3 (C). Closed circles are the experimental values for DNSA binding in the presence of ibuprofen (A, B; 20μM, C; 24μM). Solid line represents theoretical curves assuming the independent binding of the two ligands. Broken line represents theoretical curves assuming competitive binding between DNSA and ibuprofen. Dotted line represents theoretical curves assuming anti-cooperative (allosteric) interaction between DNSA and ibuprofen. All theoretical curves were constructed using the association constant for each ligand (A; DNSA 1.2×10⁵ M^-1, ibuprofen 37.1×10⁵ M^-1, B; DNSA 1.3×10⁵ M^-1, ibuprofen 26.7×10⁵ M^-1, C; DNSA 1.7×10⁵ M^-1, ibuprofen 6.8×10⁵ M^-1).</p

Effects of Ole on coupling constant (χ) for interactions between DNSA and ibuprofen.

<p>Closed circles are coupling constants calculated from the binding of DNSA in the presence of ibuprofen. Open circles are coupling constants calculated from the binding of ibuprofen in the presence of DNSA. The results are the mean ± S.D. for at least four determination.</p

Docking data of ligands-HSA complexes.

<p>Docking data of ligands-HSA complexes.</p