*Article* **In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells**

**Robert Rednic 1, Iasmina Marcovici 2,3, Razvan Dragoi 1,\*, Iulia Pinzaru 2,3,\*, Cristina Adriana Dehelean 2,3, Mirela Tomescu 1, Diana Aurora Arnautu 1, Marius Craina 1, Adrian Gluhovschi 1, Mihaela Valcovici <sup>1</sup> and Aniko Manea <sup>1</sup>**


**Abstract:** *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 hepatotoxicity 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.

**Keywords:** labetalol; folic acid; folate; dietary supplements; cytotoxicity
