Study of feasibility of the treatment with procainamide hydrochloride and cisplatin in pregnant mice.
Cisplatin is one of the most widely utilized anticancer drugs; nevertheless its use is often hampered by the onset of serious side effects. In spite of its tight binding to DNA, great teratogenic effects do not characterize cisplatin, although its embryolethal and growth retardation activities are quite remarkable. On the basis of our previous observations, demonstrating the usefulness of procainamide hydrochloride for the protection against cisplatin toxic effects in adult mice and rats, we now analyze the feasibility of the combined treatment with cisplatin and the antiarrhythmic drug procainamide hydrochloride in pregnant mice and the possible protective action of procainamide against the embryotoxic activity of cisplatin. Our data, obtained in CD-1 dams after treatment with 8 or 12 mg/kg cisplatin ip, with or without 50 mg/kg procainamide hydrochloride iv, confirm the embryotoxic effects of cisplatin. We also demonstrate that procainamide may be administered with cisplatin without causing an increase in its embryotoxic effects, but slightly improving some embryotoxicity parameters in living embryos such as the fetal weight, the percentage of fetuses with skeletal anomalies, and the number of ossification centres. The mechanism of action of this partially protective activity seems to be linked in part to the lower cisplatin accumulation in fetal tissue, probably due to an interaction of drugs at the level of placenta, in part to the protection of procainamide against maternal toxicity of cisplatin. A relevant result of this research is the suggestion that procainamide hydrochloride might be administered in case of pregnancy to protect against the maternal toxic effects of cisplatin without an increased embryotoxic/teratogenic risk for the offspring.
Ognio
Emanuela
E
Istituto Nazionale per la Ricerca sul Cancro, SS Sperimentazioni su Modelli Animali, Lgo R Benzi, 10, 16132 Genova, Italy.
Chiavarina
Barbara
B
Peterka
Miroslav
M
Mariggiò
Maria A
MA
Viale
Maurizio
M
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D020964:Embryo Loss / Q000139:chemically induced; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011342:Procainamide / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D011342:Procainamide; D002945:Cisplatin