N, N-Dimethylacetamide (DMA) Controls Infection-Associated Preterm Birth
Sandra E. Reznik, College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences
Abstract:
Background: Preterm birth (PTB) currently accounts for 12.3% of all births in the United States, with the leading cause of PTB being maternal infection. The lack of FDA approved treatments for PTB has spurred research efforts aimed at understanding the pathogenesis of PTB and developing new therapeutic approaches.
Objective: Our aim was to assess the tocolytic effects of N,N-dimethylacetamide (DMA) in infection-associated PTB.
Methods: At 15 days’ gestation C57BL/6 mice were administered lipopolysaccharide (LPS) (50mg/kg) intraperitoneally (ip) to induce PTB. A 0.5 mL injection of increasing concentrations (12.5% (n=8), 25% (n=10), 50% (n=6), 100% (n=8)) of DMA was administered ip 30 minutes prior to, and 10 hours after the LPS injection. The controls received phosphate buffered saline (PBS) instead (n=9). Histological sections of placenta and uteri from both treated and control groups were analyzed for extent of inflammatory infiltrate, using light microscopy for inflammatory cells.
Results: Mice treated with DMA showed a significant decrease in the percent mice delivering prematurely and the percent of pups dropped, compared to controls, for all concentrations of DMA (p<0.001 for 100%, 50% and 25%; p<0.05 for 12.5%). Preliminary histological analysis showed a decrease in the number of inflammatory cells in placental sections of DMA-treated mice relative to control.
Conclusions: In conclusion, DMA was effective in preventing infection-associated PTB and showed a dose response relationship. Gestational tissues from mice treated with DMA showed decreased numbers of inflammatory cell infiltrates as compared to controls. These results suggest that DMA may act as tocolytic agent via an anti-inflammatory mechanism.