F. Bartoli Klugmann

Adriamycin experimental cardiomyopathy in Swiss mice. Different effects of two calcium antagonistic drugs on ADM - induced cardiomyopathy.

Summary The effects of two calcium antagonistic drugs, verapamil (V) and nifedipine (N), on the experimental cardiomyopathy induced by adriamycin (ADM) in Swiss mice have been tested. The study was performed by monitoring the survival time of the animals and by evaluating the histologic cardiac changes. We have shown that the two drugs do not protect against the development of the cardiomyopathy; N moreover accentuates the cardiotoxic effect of ADM; perhaps N and ADM have synergic effects on myocardial calcium metabolism.

Effects of ICRF 159 on adriamycin-induced cardiomyopathy in rats.

The effect of ICRF 159 on adriamycin (ADR) cardiotoxicity and on total myocardial calcium content was examined in rats. ICRF 159 did not increase the survival time of ADR-treated animals; however the histological findings showed a significant prevention of ADR-induced cardiomyopathy (CMP) by ICRF. The total myocardial calcium content of animals treated with ADR was significantly higher, while no significant difference was seen in animals pretreated with ICRF 159 as compared with controls. As these findings suggested a role of calcium in ADR CMP and in the pharmacological action of ICRF in this disease, we also tested a closely related chelating agent, EDTA. This molecule decreased myocardial calcium levels in ADR-treated animals almost to normal values; however the histological cardiac alterations were not prevented.

Interaction of adriamycin with rat and mouse mast cells: Histamine release and cellular uptake

In the present study, we evaluated in mouse and rat mast cells if adriamycin uptake is related to histamine release. In addition, the uptake of the antineoplastic drug and histamine release were studied in other normal and neoplastic cell lines. The effect of sodium cromoglycate was also examined.Adriamycin induced histamine release from mixed or purified mast cells of the mouse and rat. This exocytotic response was quantitatively related to intracellular concentrations of adriamycin. Significant differences in adriamycin uptake were observed between mast cells and other normal and neoplastic cells. When peritoneal mast cells were treated with sodium cromoglycate, histamine release and adriamycin uptake were significantly reduced. In contrast, incubation of other cells with cromoglycate only slightly reduced the cellular concentration of the antineoplastic drug.

Anticonvulsant activity of two polyethylene glycols in mice

The anticonvulsant activity of two polyethylene glycols of different molecular weight (400 and 4000) was tested in mice. The two substances were inactive in the maximal electroshock test, but, when intraperitoneally administered, were efficacious in the pentetrazole and strychnine seizure tests. Polyethylene glycol 4000 showed the most potent anticonvulsant action. On the contrary, when polyethylene glycols were orally administered, they did not alter the time for seizure onset and for death.

Impairment of motor coordination induced by doxorubicin in mice.

The neurotoxic effects of a single intraperitoneal or intravenous injection of doxorubicin were evaluated in CD1 mice by means of the rotarod test. The test was performed daily for nine weeks after treatment. For both routes of administration, animals were treated with various doxorubicin dosages ranging from 18 to 5.9 mg/kg. The three higher i.v. doses (18, 14.4 and 12.5 mg/kg) of doxorubicin induced a severe motor coordination impairment. The histopathological analysis of these animals showed severe damage of sensory nerves. On the contrary, all the i.p. treated animals did not show any sign of motor impairment and of appreciable neurohistological lesion.

Evidence for the lack of involvement of free radicals in adriamycin-induced histamine release from rat peritoneal cells

The antineoplastic drug adriamycin, at a concentration of 100 μg/ml, caused a significant histamine release from rat peritoneal mast cells. This exocytotic process was unaffected by pretreatment with various concentrations of catalase, superoxide-dismutase,d-mannitol, alpha-tocopherol and reduced glutathione. Only very high concentrations of n-acetylcysteine significantly limited this release; this substance was also active in limiting histamine secretion induced by a classic mast cell secretagogue, compound 48/80.

Effects of transition metal complexes on human lymphocyte blastogenesis in vitro.

Summary The effect of two Platinum (II), two Rhodium (I), and two Ruthenium (II) complexes on the in vitro blastogenic response of human peripheral lymphocytes has been tested. All compounds except Ru(II) (DMSO) 2 o -phen-Cl 2 strongly inhibit the blastogenic response stimulated by mixed culture and by PHA. In the discussion of the results special emphasis is given to the pronounced difference between inhibition of PHA- and mixed culture-stimulated lymphocytes shown by the two platinum compounds.