Thalidomide remodels developing heart in chick embryo: discovery of a thalidomide mediated hematoma in heart muscle.
Pavitra KumarHarish A KumarLakshmikirupa SundaresanAnuran GhoshPriyadarshan KathirvelApurva ThilakYash T KatakiaKavitha SankaranarayananSuvro ChatterjeePublished in: Naunyn-Schmiedeberg's archives of pharmacology (2018)
Despite of medical disaster caused by thalidomide in 1960s, the drug came to clinical use again for the treatment of erythema nodosum leprosum (ENL) and multiple myeloma. Recently, a new generation of children affected by thalidomide intake by their mothers during pregnancy has been identified in Brazil. In the past few years, there is the great enhancement in our understanding of the molecular mechanisms and targets of thalidomide with the help of modern OMICS technologies. However, understanding of cardiac-specific anomalies in fetus due to thalidomide intake by the respective mother has not been explored fully. At organ level, thalidomide causes congenital heart diseases, limb deformities in addition to ocular, and neural and ear abnormalities. The period of morning sickness and cardiogenesis is synchronized in pregnant women. Therefore, thalidomide intake during the first trimester could affect cardiogenesis severely. Thalidomide intake in pregnant women either causes miscarriage or heart abnormalities such as patent ductus arteriosus, ventricular septal defect (VSD), atrial septal defect (ASD), and pulmonary stenosis in survivors. In the present study, we identified a novel morphological defect (lump) in the heart of thalidomide-treated chick embryos. We characterized the lump at morphological, histo-pathological, oxidative stress, electro-physiological, and gene expression level. To our knowledge, here, we report the very first electrophysiological characterization of embryonic heart affected by thalidomide treatment.
Keyphrases
- pregnant women
- heart failure
- gene expression
- oxidative stress
- healthcare
- multiple myeloma
- young adults
- dna methylation
- weight gain
- emergency department
- left ventricular
- attention deficit hyperactivity disorder
- dna damage
- body mass index
- skeletal muscle
- physical activity
- signaling pathway
- combination therapy
- ischemia reperfusion injury
- weight loss
- optical coherence tomography
- pregnancy outcomes
- drug induced
- high speed
- electronic health record
- heat shock protein