[Histofluorometric studies of nervous lesions induced with daunomycin in the ileum and colon of the rat and guinea pig].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
M C Breschi
Publications and source records attributed to M C Breschi.
QT prolongation in anaesthetized guinea-pigs: an experimental approach for preliminary screening of torsadogenicity of drugs and drug candidates.
Many non-cardiovascular drugs can prolong the QT interval of the electrocardiogram (ECG); this is an accessory property not necessary for their pharmacological action and generally linked to the block of the potassium HERG channels and delayed cardiac repolarization. The QT prolongation can lead to a dangerous tachyarrhythmia, called torsade de pointes, and potentially to fatal ventricular fibrillation. The experimental approaches, aimed at an early identification of this undesidered property, often require sophisticated and expensive equipment or the use of superior animal species (dog, primates) that cannot be employed easily for ethical and/or economic reasons. This work aimed to study drug-induced QT prolongation in anaesthetized guinea-pigs and to evaluate the reliability of such an experimental approach to obtain a satisfying predictive parameter of the torsadogenicity of drugs in humans. Seven drugs that were torsadogenic in humans (astemizole, cisapride, haloperidol, quinidine, sotalol, terfenadine and thioridazine) and two that were non-torsadogenic (chlorprotixene and diazepam) were administered i.v. to guinea-pigs under pentobarbital anaesthesia. The ECGs were recorded by four electrodes inserted in the subcutaneous layer of the limbs. Both RR and QT intervals were measured in Leads II and III and then the correct QT values were calculated by Bazett and Fridericia algorithms (QTcB and QTcF, respectively). All the drugs, with the exception of chlorprotixene and diazepam, produced a dose-dependent prolongation of the QT and RR intervals and a significant increase of QTcB and QTcF values. It can be concluded that this method represents a rapid and low-cost procedure to evaluate the cardiac safety pro fi le in the preliminary screening of a high number of drugs or drug candidates.
Animals↗
Effect of reserpine and calcium antagonists on doxorubicin storage in various organs of young and senescent rats.
Reserpine pre-treatment causes a considerable decrease in typical red-orange doxorubicin fluorescence of the organs examined (kidney, large intestine, spleen) and a similar picture is observed after calcium antagonists administration. This effect is far more evident in the spleen and large intestine than in the kidney; moreover, it seems more marked in young rats compared with aged ones. An inhibitory action of these drugs on the anthracycline transport carrier through the cell membrane is hypothesized.
Aging↗
Doxorubicin storage in myocardial tissue of reserpine- and nicardipine-pretreated rats.
While reserpine and nicardipine pretreatment induced a more or less marked decrease in typical red-orange doxorubicin fluorescence in certain rat tissues, such as spleen, kidney and large intestine, the myocardial tissue (right atrium and left ventriculum) did not show any significant variations in nuclear doxorubicin storage. This different behaviour of cardiac tissue may be related to the well-known doxorubicin cardiotoxicity.
Animals↗
Comparative histochemical study of adriamycin and adriamycinol in rat liver and heart.
Investigations were carried out into morphological differences between the uptake of adriamycin and its 13-OH metabolite adriamycinol into rat liver and heart. In the liver parenchyma, adriamycinol is mainly stored in the central area of the hepatic lobule, while adriamycin shows a more uniform distribution. In cardiac tissue, adriamycin accumulates within chromatin masses, whereas adriamycinol scarcely enters myocardial cells. The cardiotoxicity of both anthracyclines might be related to interactions with cytomembrane binding sites.
Animals↗