Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments

Kis, Andreea M.; Macaşoi, Ioana; Paul, Corina; Rădulescu, Matilda; Buzatu, Roxana; Watz, Claudia; Cheveresan, Adelina; Berceanu, Delia; Pînzaru, Iulia; Dinu, Ștefania; Manea, Aniko; Poenaru, Mărioara; Borza, Claudia; Dehelean, Cristina

doi:10.3390/medicina58020167

Cited by 16 publications

(10 citation statements)

References 54 publications

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“…A stereomicroscope was used to observe the vascular effects (Discovery 8 Stereomicroscope from Zeiss, Göttingen, Germany) and images were taken with an Axio CAM 105 color camera from Zeiss 5 min before and after application of the samples. To quantify the irritant effect at the vascular level, the analytical method of calculating the irritation score (IS) was applied using the formula described above [ 19 ]:

…”

Section: Methodsmentioning

confidence: 99%

Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels

Chioran

Sitaru

Macaşoi

et al. 2022

IJERPH

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The use of tobacco products is a major global public health issue, as it is the leading cause of preventable death worldwide. In addition, nicotine (NIC) is a key component of electronic and conventional cigarettes. Although nicotine’s addictive potential is well known, its health effects are not entirely understood. Thus, the main objective of the present study was to evaluate its toxicological profile both in vitro, at the level of three healthy cell lines, and in ovo, at the level of the chorioallantoic membrane. Five different concentrations of nicotine were used in keratinocytes, cardiomyocytes, and hepatocytes for the purpose of evaluating cell viability, cell morphology, and its impact on nuclei. Additionally, the hen’s egg test on the chorioallantoic membrane (HET-CAM) method was used to assess the biocompatibility and irritant potential of the chorioallantoic membrane. Across all cell lines studied, nicotine was proven to be significantly damaging to cell viability, with the highest concentration tested resulting in less than 2% viable cells. Moreover, the morphology of cells changed dramatically, with alterations in their shape and confluence. Nicotine-induced cell death appears to be apoptotic, based on its impact on the nucleus. In addition, nicotine was also found to have a very strong irritating effect on the chorioallantoic membrane. In conclusion, nicotine has an extremely strong toxicological profile, as demonstrated by the drastic reduction of cell viability and the induction of morphological changes and nuclear alterations associated with cellular apoptosis. Additionally, the HET-CAM method led to the observation of a strong irritating effect associated with nicotine.

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…”

Section: Methodsmentioning

confidence: 99%

Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels

Chioran

Sitaru

Macaşoi

et al. 2022

IJERPH

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“…Using the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay, the potential in ovo toxicity of the samples was evaluated. This experiment was conducted according to the protocol described above, involving the following steps: 1) on the 10th day of incubation, at the vascular plexus of the chorioallantoic membrane, RUT-O and RUT-L, at a concentration of 100 µM along with a positive control (sodium dodecyl sulphate, 1%) and a negative control -distilled water, were applied; 2) a volume of 600 μl of each sample was added in order to ensure the complete coverage of the chorioallantoic membrane; 3) the following changes in the blood vessels were noted through a 5 minutes monitorization: hemorrhage (H), lysis (L) and coagulation (C); 4) for each sample, the time of the vascular changes was noted, then irritation was calculated according to the formula (Batista-Duharte et al, 2016;Kis et al, 2022).…”

Section: In Ovo Irritant Potentialmentioning

confidence: 99%

Rutin bioconjugates as potential nutraceutical prodrugs: An in vitro and in ovo toxicological screening

et al. 2022

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Rutin (RUT) is considered one the most attractive flavonoids from a therapeutic perspective due to its multispectral pharmacological activities including antiradical, anti-inflammatory, antiproliferative, and antimetastatic among others. Still, this compound presents a low bioavailability what narrows its clinical applications. To overcome this inconvenience, the current paper was focused on the synthesis, characterization, and toxicological assessment of two RUT bioconjugates obtained by enzymatic esterification with oleic acid (OA) and linoleic acid (LA)—rutin oleate (RUT-O) and rutin linoleate (RUT-L), as flavonoid precursors with improved physicochemical and biological properties. Following the enzymatic synthesis in the presence of Novozyme® 435, the two bioconjugates were obtained, their formation being confirmed by RAMAN and FT-IR spectroscopy. The in vitro and in ovo toxicological assessment of RUT bioconjugates (1–100 µM) was performed using 2D consecrated cell lines (cardiomyoblasts - H9c2(2-1), hepatocytes—HepaRG, and keratinocytes—HaCaT), 3D reconstructed human epidermis tissue (EpiDerm™), and chick chorioallantoic membranes, respectively. The results obtained were test compound, concentration—and cell-type dependent, as follows: RUT-O reduced the viability of H9c2(2-1), HepaRG, and HaCaT cells at 100 µM (to 77.53%, 83.17%, and 78.32%, respectively), and induced cell rounding and floating, as well as apoptotic-like features in the nuclei of all cell lines, whereas RUT-L exerted no signs of cytotoxicity in all cell lines in terms of cell viability, morphology, and nuclear integrity. Both RUT esters impaired the migration of HepaRG cells (at 25 µM) and lack irritative potential (at 100 µM) in vitro (tissue viability >50%) and in ovo (irritation scores of 0.70 for RUT-O, and 0.49 for RUT-L, respectively). Computational predictions revealed an increased lipophilicity, and reduced solubility, drug-likeness and drug score of RUT-O and RUT-L compared to their parent compounds—RUT, OA, and LA. In conclusion, we report a favorable toxicological profile for RUT-L, while RUT-O is dosage-limited since at high concentrations were noticed cytotoxic effects.

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“…The wound widths were measured at the end of the treatment with CellSense Dimension 1.17 (Olympus, Tokyo, Japan). The quantification of the effects in terms of cell migration was performed by calculating the wound healing rates (%) according to a formula used in our previous work [23,24].…”

Section: Wound Regenerationmentioning

confidence: 99%

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

et al. 2022

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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.

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Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments

Cited by 16 publications

References 54 publications

Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels

Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels

Rutin bioconjugates as potential nutraceutical prodrugs: An in vitro and in ovo toxicological screening

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

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