Commonly Used Nonsteroidal Anti-inflammatory Drug (NSAIDs) in Obstetrics and Associated Placental Cytotoxicity [ID 912]

INTRODUCTION: The objective was to determine whether commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) have a cytotoxic effect and their ability to reduce inflammation at the cellular level of the feto-maternal interface. METHODS: A microfluidic fetal membrane–placental feto-maternal interface on-chip (FMi-PLA-OOC) composed of seven different cell types was used to analyze the effects of cell cytotoxicity at the placental–maternal interface with therapeutic concentrations of commonly used NSAIDs in obstetrics. Therapeutic concentrations of aspirin (2 micrograms/mL corresponding to 81 mg) and indomethacin (15 micrograms/mL) were applied to the FMi-PLA-OOC with the supernatants analyzed for lactate dehydrogenase levels and cytokine levels in both a diseased state, nondiseased state (simulated with lipopolysaccharide [LPS]), and a diseased state with treatment of the NSAIDs. RESULTS: Cell cytotoxicity in the control group was approximately 20% in AEC, AMC, CTC, and STB cell lines. After application of LPS, the cell cytotoxicity increased in five cell types. Aspirin decreased cell death by approximately 84% in AEC and 48.7% in STB. However, indomethacin increased cell death across all cell lines. A three-way ANOVA was conducted with P <.0001. Proinflammatory cytokine IL-8 was decreased with aspirin use. CONCLUSIONS/IMPLICATIONS: Indomethacin demonstrates cell cytotoxicity at all layers of the feto-maternal interface. On the other hand, aspirin demonstrated an improvement in cell death in a diseased state which can support the continued use of aspirin for the promotion of placental angiogenesis. Aspirin also demonstrated a decrease in proinflammatory cytokines at the placental cellular level.