Cetirizine more potently exerts mast cell-stabilizing property than diphenhydramine.

Cetirizine, a second-generation antihistamine, and diphenhydramine, a first-generation antihistamine, are among the most widely used anti-allergic drugs. In addition to longer duration of action and less incidence of sedative side effects, recent clinical studies also indicate a higher potency of cetirizine than diphenhydramine in the treatment or prevention of allergic disorders. In the present study, using the differential-interference contrast (DIC) microscopy, we examined the effects of cetirizine and diphenhydramine (1 µM to 1 mM) on the degranulation from rat peritoneal mast cells. Using fluorescence imaging of a water-soluble dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. At relatively higher concentrations (100 µM, 1 mM), both cetirizine and diphenhydramine significantly reduced the numbers of degranulating mast cells. Of note, at 1 mM, cetirizine more markedly reduced the number than diphenhydramine, almost entirely suppressing the degranulation of mast cells. Additionally, 1 mM cetirizine and levocetirizine, another second-generation antihistamine, almost totally inhibited the process of exocytosis in mast cells and washed out the trapping of the lucifer yellow on the cell surface, while diphenhydramine and chlorpheniramine, another first-generation antihistamine, did not. This study provided in vitro evidence for the first time that cetirizine more potently inhibited the process of exocytosis in mast cells than diphenhydramine, indicating its higher potency as a mast cell-stabilizer. Such mast cell-stabilizing property of cetirizine could be ascribed to its counteracting effect on the plasma membrane deformation in degranulating mast cells.

Subepicardial burn injuries in bullfrog heart induce electrocardiogram changes mimicking inferior wall myocardial infarction.

Using bullfrog hearts, we previously reproduced a ST segment elevation in electrocardiogram (ECG), mimicking human ischemic heart disease. In the present study, by inducing subepicardial burn injuries on the inferior part of the frog heart ventricle, we could reproduce typical ECG changes observed in human inferior wall myocardial infarction, such as the marked elevation of the ST segments in inferior limb leads (II, III, aVF) and their reciprocal depression in the opposite limb leads (I, aVL). Due to the decrease in Na+/K+-ATPase protein expression, the resting membrane potential of injured cardiomyocytes shifted toward depolarization. Such induced electrical difference between the injured and intact cardiomyocytes was thought to be responsible for the creation of "currents of injury" and the subsequent ST segment changes.