Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No.2, 300041 Timisoara, Romania.
Faculty of Pharmacy, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No.2, 300041 Timisoara, Romania.
Medicina (Kaunas). 2022 Jun 10;58(6):784. doi: 10.3390/medicina58060784.
Background and Objectives: The consumption of dietary supplements has increased over the last decades among pregnant women, becoming an efficient resource of micronutrients able to satisfy their nutritional needs during pregnancy. Furthermore, gestational drug administration might be necessary to treat several pregnancy complications such as hypertension. Folic acid (FA) and folate (FT) supplementation is highly recommended by clinicians during pregnancy, especially for preventing neural tube birth defects, while labetalol (LB) is a β-blocker commonly administered as a safe option for the treatment of pregnancy-related hypertension. Currently, the possible toxicity resulting from the co-administration of FA/FT and LB has not been fully evaluated. In light of these considerations, the current study was aimed at investigating the possible in vitro cardio- and hepato-toxicity of LB-FA and LB-FT associations. Materials and Methods: Five different concentrations of LB, FA, FT, and their combination were used in myoblasts and hepatocytes in order to assess cell viability, cell morphology, and wound regeneration. Results: The results indicate no significant alterations in terms of cell viability and morphology in myoblasts (H9c2(2-1)) and hepatocytes (HepaRG) following a 72-h treatment, apart from a decrease in the percentage of viable H9c2(2-1) cells (~67%) treated with LB 150 nM−FT 50 nM. Additionally, LB (50 and 150 nM)−FA (0.2 nM) exerted an efficient wound regenerating potential in H9c2(2-1) myoblasts (wound healing rates were >80%, compared to the control at 66%), while LB-FT (at all tested concentrations) induced no significant impairment to their migration. Conclusions: Overall, our findings indicate that LB-FA and LB-FT combinations lack cytotoxicity in vitro. Moreover, beneficial effects were noticed on H9c2(2-1) cell viability and migration from LB-FA/FT administration, which should be further explored.
在过去几十年中，孕妇对膳食补充剂的消费有所增加，成为满足其妊娠期间营养需求的有效微量营养素来源。此外，为了治疗妊娠高血压等多种妊娠并发症，可能需要进行妊娠期药物治疗。临床医生强烈建议孕妇补充叶酸（FA）和叶酸盐（FT），尤其是为了预防神经管出生缺陷，而拉贝洛尔（LB）是一种β受体阻滞剂，常用于治疗妊娠相关高血压的安全选择。目前，尚未充分评估 FA/FT 和 LB 联合用药可能产生的毒性。有鉴于此，本研究旨在研究 LB-FA 和 LB-FT 联合用药的潜在体外心脏毒性和肝脏毒性。
使用五种不同浓度的 LB、FA、FT 及其组合，评估其对肌母细胞和肝细胞的细胞活力、细胞形态和伤口再生的影响。
结果表明，在 72 小时的处理后，肌母细胞（H9c2(2-1)) 和肝细胞（HepaRG）的细胞活力和形态均无显著变化，除了 LB 150 nM-FT 50 nM 处理的 H9c2(2-1)细胞的存活率降低（~67%）。此外，LB（50 和 150 nM）-FA（0.2 nM）在 H9c2(2-1)肌母细胞中表现出有效的伤口再生潜力（伤口愈合率>80%，而对照组为 66%），而 LB-FT（在所有测试浓度下）对其迁移没有显著的损害。
总体而言，我们的研究结果表明，LB-FA 和 LB-FT 联合用药在体外无细胞毒性。此外，LB-FA/FT 给药对 H9c2(2-1)细胞活力和迁移有有益的影响，这需要进一步探索。
