title: Role of apoptosis in mediating diclofenac-induced teratogenesis: An in vitro approach.
abstract: Diclofenac (DCF) is among the most commonly used nonsteroidal anti-inflammatory drugs worldwide for the treatment of various conditions in postpubertal women. However, very limited information is available regarding its safety during pregnancy and teratogenecity. The present study was designed to elucidate the effects of DCF on the developing rat embryos during the major organogenesis period and investigate the critical role of apoptosis in bringing about these congenital anomalies. Embryos were exposed in vitro to various concentrations of DCF, that is, 0, 3.75, 7.5 and 15 µg/ml for 24 h, respectively, and examined for the growth and differentiation at the end of the culture period for the presence of any specific malformations. Growth and developmental parameters such as weight of embryos, crown-rump length and number of somites were found to be lower in the embryos exposed to high concentrations of DCF (7.5 and 15.0 μg/ml) when compared with the untreated control. However, no significant difference in growth parameters was found between embryos exposed to 3.75 µg/ml and the control group. In parallel to this, flow cytometric analysis and DNA quantitation of cultured rat embryos were performed to verify the involvement of apoptosis in mediating DCF-induced teratogenesis. A concentration-dependent increase in apoptosis in embryos suggests a possible engagement of apoptosis in the role of DCF as a teratogenic agent. A detailed analysis of the actual effect of DCF on cellular apoptotic machinery necessitates further evaluation.
authors: Present address: LSU Health Sciences Center, New Orleans, LA, USA CSIR (Central Drug Research Institute), Lucknow, India gyancdri@gmail.com n_sinha@cdri.res.in.
authors: Gyanendra
authors: G
authors: Singh
authors: CSIR (Central Drug Research Institute), Lucknow, India.
authors: Ranjeeta
authors: R
authors: Maurya
authors: CSIR (Central Drug Research Institute), Lucknow, India.
authors: Akhilesh
authors: A
authors: Kumar
authors: CSIR (Central Drug Research Institute), Lucknow, India.
authors: Neeraj
authors: N
authors: Sinha
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D004008:Diclofenac / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D005434:Flow Cytometry; D066298:In Vitro Techniques; D011897:Random Allocation; D051381:Rats; D064793:Teratogenesis / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac
keywords: Apoptosis; diclofenac (DCF); embryo culture; in vitro