Role of apoptosis in mediating salicylic acid-induced teratogenesis in vitro.
Salicylic acid (SAL) is among the most commonly used drugs worldwide and is known to cause congenital malformations and fetal death in animals. In this study, the effect of SAL on major organogenesis period and the role of apoptosis in mediating congenital malformations have been carried out. In the present study, post-implantation rat embryos of day 11 were cultured for 24 h with various concentrations of SAL, i.e. 10, 100, and 1000 microg/ml cultures, respectively. The growth and developmental of each embryo was evaluated and compared with control ones for the presence of any malformations. The SAL decreased all growth and developmental parameters in a concentration-dependent manner, when compared with control. However, exposure to SAL at 10 microg/ml culture did not show any significant effect on embryonic growth and development. Parallel to this, flow cytometric analysis (cell cycle and annexin V binding) and DNA fragmentation assay were carried out followed by quantitation by 3'-OH labeling of cultured rat embryos to evaluate the role of apoptosis in bringing about SAL-induced teratogenesis. All results were found to be dose-dependent and an increase in apoptosis in embryonic tissues may be related to the increased risk of congenital malformations. The data suggested that apoptosis might be involved in mediating teratogenesis of SAL in vitro.
Division of Toxicology, Central Drug Research Institute, Lucknow, India. gyancdri@gmail.com
Gyanendra
G
Singh
Neeraj
N
Sinha
Mahipal Gurram
MG
Sinnollareddy
D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D006801:Humans; D011247:Pregnancy; D051381:Rats; D020156:Salicylic Acid / Q000494:pharmacology*; D013723:Teratogens / Q000494:pharmacology*; D046509:Tissue Culture Techniques
D000890:Anti-Infective Agents; D013723:Teratogens; D020156:Salicylic Acid