Effects of doxorubicin on the developing brain of albino mice embryos

Abstract

Doxorubicin is an anthracycline antineoplastic drug. It has been widely used in the treatment of many malignancies including haematological malignancies, soft tissues sarcomas, breast cancer and neuro-blastoma etc. The doxorubicin rat model is an established model which encompasses spectrum of anomalies seen in VACTERAL associations and has similarities to human VACTER anomalies. The aim of present study is to support the anomalies produced by doxorubicin in albino mice embryos. Material and Methods: The present study was conducted in the department of anatomy, IMS, BHU Varanasi, U.P, on fifty female albino mice of an average age of 80 to 100 days, kept in plastic cage with male (3female:1male) in aseptic air condition. After confirming the pregnancy, the drug was administered intraperitoneally on the 8 th day of gestation in a dose of 3mg/kg body weight. The foetuses were collected by exteriorization of uterine horn on 19 th day of gestation and examined for congenital anomalies. Observations: Foetuses were divided into two groups, control and treated. Out of 239 treated foetuses, 25 foetuses were found dead, 106 foetuses showed congenital anomalies and the rest 108 foetuses were found normal. The brains of treated foetuses were smaller and reduced in weight (microcephaly) as compared to average weight and size of brain of control foetuses. On histological examination, cerebrum and cerebellum showed degeneration and aggregation of neuronal cells. Conclusions: The drug was found to be lethal as well as teratogenic in developing mice embryos. Since, mice are the foremost mammal model for researchers; the present study also establishes doxorubicin mouse model support to the well established adriamycine rat model for VACTERL anomalies.