Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells.

Betulinic acid, a small molecule from pentacyclic triterpenes class, has been widely studied for its antitumor activity, revealing that it induces the apoptosis of tumor cells in a selective manner. In recent years, digoxin, a cardiac glycoside found particularly in the plant species Digitalis lanata, has drawn interest for its potential antitumor properties. The present study was designed to evaluate the antimelanoma potential of betulinic acid (BA), digoxin (DG), and their association (DG + BA). In vitro assessments were performed 24 h post-treatment on two human melanoma cell lines (SK-Mel-28 and RPMI-7951). In addition, the potential irritant effects of the test samples were evaluated using the chorioallantoic membrane of hen's eggs. BA and DG exhibit a concentration-dependent cytotoxic activity, with the combination of the two having a more marked effect on the decrease in cell viability (~17% for SK-Mel-28 cells and ~23% for RPMI-7951 cells). Further, morphological changes (rounding of the cells and their separation from the plaque) and alterations in the nucleus and actin fibers (condensation of chromatin and actin fibers, formation of apoptotic bodies) were observed, indicating an apoptotic-like process. Moreover, no irritating effects were observed in ovo. As a result, DG + BA acid may have synergistic potential in the antitumor treatment of melanoma, but future studies are needed in order to clarify the biological mechanisms involved.

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

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 ß-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.

A rare case of Meckel-Gruber syndrome.

Meckel-Gruber syndrome (MKS) is a lethal, autosomal recessive transmitted anomaly, characterized by the ultrasound triad: occipital meningoencephalocele, bilateral polycystic kidney, postaxial polydactyly. The incidence is between 1÷13 250 and 1÷140 000 live births, being a rare anomaly. We report a MKS case of feminine gender diagnosed on two ultrasound findings (bilateral polycystic kidney, occipital meningoencephalocele). This case highlights the presence of MKS in a young female without family history.