Hugo Molina

Comparison of Lipid Peroxidation and Myocardial Damage Induced by Adriamycin and 4′-Epiadriamycin in Mice

Adriamycin (ADM) and 4′-epiadriamycin (4′-ADM) were given to mice in a single dose of 15 mg/kg body weight (i.p.). Twenty-five mice were alloted to 3 groups. One group (Group I; n = 8) was given ADM; another group (Group II; n = 9) was similarly treated with 4′-ADM, and a control group (n = 8) received an equivalent volume of 0.9 % NaCl solution. Mice were sacrificed 4 days after the described treatment. A complete autopsy was carried out in each animal. Hydroperoxide-initiated chemihuninescence and malonaldehyde formation were measured in mouse heart homogenates. Control mice showed a maximal photoemission of 52 ± 2 (×10–3) (mean values ± S.E.M.) cpm/mg protein and a formation of 20 ± 4 nmol malonaldehyde/g organ after a 2 hr-incubation. The ADM-treated mice showed a 24 % enhanced hydroperoxide-initiated photoemission and a 370 % increased malonaldehyde formation. The 4′-ADM-treated mice showed a 15 % increased hydroperoxide-stimulated chemiluminescence and an 85 % increased malonaldehyde formation. Vitamin A (5000 IU), vitamin E (85 IU) and vitamins A and E (same doses as before) given as a single dose i.p. 1 day before doxorubicin administration were able to decrease the hydroperoxide-initiated chemihuninescence by 24 %, 26 % and 44 %, respectively. Microscopically, only scarce isolated microvacuolated subendocardial fibers were found in the ADM-treated animals. Our data showing that 4′-ADM lacks a statistically significant effect in increasing heart peroxidation as compared to ADM may explain its lower myocardial toxicity.

Amelioration of adriamycin-induced cardiotoxicity in rabbits by prenylamine and vitamins A and E.

The cardioprotective potentials of prenylamine (a calcium antagonist) and of a combination of vitamins A and E (a singlet oxygen quencher and a free radical scavenger, respectively) were evaluated in rabbits given chronically large doses of Adriamycin (ADM) (10.8 mg/kg body weight for 9 to 11 weeks). Among ADM-treated rabbits, 8 of 10 showed post-treatment ECG changes; in rabbits treated with ADM and prenylamine, changes were found in a smaller number (5 of 10); and in animals treated with ADM and vitamins A and E, the incidence was only one in six (p less than 0.05). Heart homogenates from ADM-treated rabbits showed an increased hydroperoxide-initiated chemiluminescence (expressed as cpm/mg protein X 10(-3)) of 77 +/- 4 compared to control animals (52 +/- 1) (p less than 0.01). Prenylamine administration did not alter hydroperoxide-initiated chemiluminescence in ADM-treated rabbits, whereas treatment with a combination of vitamins A and E showed a significant decrease in hydroperoxide-initiated chemiluminescence in control (40 +/- 2) and ADM-treated rabbits (42 +/- 1). Microscopically, myocardial fibers had mild to severe hydropic vacuolization of sarcoplasm, which led to progressive myocytolysis. A total of 103 +/- 13 damaged fibers were detected over 700 counted fibers. Myocardial damage was lowered to 47 +/- 16 by administration of prenylamine and to 28 +/- 8 by administration of vitamins A and E. It is suggested that ADM leads to myocardial lipid peroxidation (ameliorated by vitamins A and E) with membrane damage and to an increase in calcium permeability, the latter being counteracted by prenylamine.

Schwannomatosis: report of a new case

Schwannomatosis is a rare disorder, still not quite well defined, seldom described in the literature. In this paper we report the case of male. Patient, 52 years old, who in the last 30 years developed five subcutaneous tumors within his limbs peripheral nerves, which histologically proved to be schwannomas. A brain computed tomography showed a partially calcified tumor in the left temporal lobe which most likely was a meningioma. A thorough clinical examination was unable to find signs of type I or type II neurofibromatosis. The present condition, probably a form of phacomatosis, has to be distinguished from neurofibromatosis and is considered as an independent clinical entity whose origin still awaits further detailed investigations.