Thalidomide remodels developing heart in chick embryo: discovery of a thalidomide mediated hematoma in heart muscle

Naunyn Schmiedebergs Arch Pharmacol. 2018 Oct;391(10):1093-1105. doi: 10.1007/s00210-018-1532-2. Epub 2018 Jul 7.

Abstract

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.

Keywords: Cardiac lump; Field potential; Heart; Thalidomide.

MeSH terms

  • Animals
  • Chick Embryo
  • Heart / drug effects*
  • Heart / embryology
  • Heart / physiology
  • Hematoma / chemically induced*
  • Hemoglobins / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Teratogens / toxicity*
  • Thalidomide / toxicity*

Substances

  • Hemoglobins
  • Reactive Oxygen Species
  • Teratogens
  • Thalidomide