Embryotoxicity of cisplatin and a cisplatin-procaine complex (DPR) studied in chick embryo
Language English Country Slovakia Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
12584587
Knihovny.cz E-resources
- MeSH
- Abnormalities, Drug-Induced etiology MeSH
- Anesthetics, Local administration & dosage pharmacology MeSH
- Cisplatin administration & dosage analogs & derivatives toxicity MeSH
- Chick Embryo abnormalities drug effects MeSH
- Organoplatinum Compounds administration & dosage toxicity MeSH
- Procaine administration & dosage analogs & derivatives pharmacology toxicity MeSH
- Antineoplastic Agents administration & dosage toxicity MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Chick Embryo abnormalities drug effects MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anesthetics, Local MeSH
- cisplatin-procaine complex MeSH Browser
- Cisplatin MeSH
- Organoplatinum Compounds MeSH
- Procaine MeSH
- Antineoplastic Agents MeSH
Cisplatin is widely used as an antitumor drug. To reduce its toxic side effects in patients, cisplatin has been bound with procaine in a cisplatin-procaine complex (DPR). The lethal and teratogenic effects of cisplatin alone and of complexed cisplatin were determined in the chick embryo in ovo in order to compare their influence on rapidly proliferating embryonic tissues. The embryotoxic (lethal + teratogenic) effect was examined after a single intra-amniotic injection of one of six different doses, ranging from 0.03 to 30.0 microg, on embryonic days (ED) 3, 4 or 5. The minimal embryotoxic dose was lower for cisplatin alone (0.03-0.3 microg) than for cisplatin in the DPR complex (0.3-3.0 microg), suggesting that cisplatin alone is more embryotoxic than complexed cisplatin. Both substances caused malformations in the surviving embryos evaluated on ED 9. These malformations included microphthalmia, microcephaly, hypoplasia of the upper and lower jaw, cleft beak, and haemocephaly. Moreover, heart septum defects and limb reduction deformities were found after exposure to the DPR complex. The embryotoxicity of complexed cisplatin exhibited a stage-response effect. It was highest on day 3 and gradually decreased until ED 5. Such an apparent stage-response effect was not observed for cisplatin alone. The embryotoxicity of procaine hydrochloride - a component of the complex - was also tested. Procaine hydrochloride alone did not produce any embryotoxic effect, not even after a single injection of the maximal tested dose (100.0 microg per embryo). We also examined the protective effect of procaine hydrochloride, whose separate administration at ED 4 was followed by the injection of 0.3 microg cisplatin. We did not observe any protective effect of procaine hydrochloride if injected separately.
