Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Sandra Rotman Centre for Global Health, University Health Network: Toronto General Hospital, Toronto, Ontario, Canada.
Parasite Immunol. 2019 Apr;41(4):e12614. doi: 10.1111/pim.12614. Epub 2019 Feb 20.
Malaria in pregnancy (MiP) alters the expression of ATP-binding cassette efflux transporters in maternal and foetal tissues, as well as the placenta. Malaria induces oxidative stress, and pregnancy is associated with arginine deficiency. We hypothesized that reducing oxidative stress during MiP by supplementation with L-arginine, a NO precursor, would attenuate transcriptional changes in a second superfamily of transporters, solute carrier (SLC) transporters, and improve pregnancy outcomes.
Pregnant BALB/c mice receiving L-arginine (1.2%) in water, or water alone, were infected with Plasmodium berghei ANKA on gestational day 13 and sacrificed on gestational day 19. Compared to controls, the mRNA of numerous SLC transporters was downregulated in maternal and foetal tissues, as well as in the placentas of infected mice. While supplementation with L-arginine did improve foetal viability, it did not improve the mRNA expression of oxidative stress markers, transporters nor other indices of foetal and maternal health. Moreover, amino acid uptake transporters were downregulated upon infection, which could potentially contribute to decreased foetal birthweight.
Malaria in pregnancy significantly alters the expression of SLC transporters in maternal and foetal tissues as well as the placenta, regardless of L-arginine supplementation. Further studies to investigate methods of reducing oxidative stress in MiP are warranted.
妊娠疟疾（MiP）改变了母体和胎儿组织以及胎盘中 ATP 结合盒外排转运蛋白的表达。疟疾会引起氧化应激，而妊娠与精氨酸缺乏有关。我们假设，通过补充一氧化氮前体 L-精氨酸来减少 MiP 期间的氧化应激，将减轻第二类转运体——溶质载体（SLC）转运体的转录变化，并改善妊娠结局。
妊娠第 13 天，给予 BALB/c 小鼠饮用水中添加或不添加 L-精氨酸（1.2%），然后在妊娠第 19 天感染伯氏疟原虫 ANKA。与对照组相比，感染小鼠的母体和胎儿组织以及胎盘中的许多 SLC 转运体的 mRNA 表达均下调。虽然 L-精氨酸的补充确实提高了胎儿的存活率，但它并没有改善氧化应激标志物、转运体以及其他胎儿和母体健康指标的 mRNA 表达。此外，感染后氨基酸摄取转运体下调，这可能导致胎儿出生体重降低。
妊娠疟疾会显著改变母体和胎儿组织以及胎盘中 SLC 转运体的表达，而无论是否补充 L-精氨酸。需要进一步研究以寻找减少 MiP 中氧化应激的方法。
