In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells
Robert RednicIasmina MarcoviciRăzvan DrăgoiIulia PînzaruCristina DeheleanMirela TomescuDiana-Aurora ArnăutuMarius CrainaAdrian GluhovschiMihaela ValcoviciAniko Maria Manea
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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.Keywords:
Viability assay
Micronutrients perform a key role in almost all vital body functions like those related to vision, immunity, bone formation, brain function and many others that help in proper growth and maintaining good health. Deficiency of any one or more of the micronutrients can have a negative impact on the overall health. The causes of micronutrient deficiencies and their signs and symptoms are explained in this chapter in a precise manner. Plant and animal food sources with high micronutrient contents with ready-to-eat food supplements per serving size are illustrated for each micronutrient. These can serve as a guideline for preventive measures and diet therapy. Micronutrients are increasingly used as an adjunct therapy in managing various health problems. Effective therapeutic uses of vitamins and minerals are exemplified for a ready reference. Overdose of synthetic supplements of micronutrients and certain environmental conditions may result in toxic effects. To address this, the upper limit for micronutrient intakes and toxic effects of excess micronutrient intakes are also described. The relevance of the yogic concept of ‘sattvic’ diet in modern nutrition and the potential of yoga for micronutrient absorption is also highlighted. The approach of yoga towards healthy diet and the relation between diet and psychological health is explained based on experimental data. The importance of specific micronutrients in health at different stages of life, from pregnancy to old age, is elucidated and remedial measures are suggested. Lastly, evidence for micronutrient supplements as an adjunct therapy for COVID-19 is briefly described. <br>
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The oxidative injury of individual QDs or Cu2+ to hepatic cells were both reported,the combined toxicity is concerned due to the co-existence of these two chemicals in human liver.We thus employed human hepatic L02 cells to test the combined toxicity of QDs and Cu2+(lower toxicity) through the cell viability decrease and cell morphology changes,meanwhile,the protective effect of antioxidant reagent NAC was used to evaluate the oxidant injury associated toxicity mechanism.The results showed that both QDs and Cu2+ could decrease the cells viability,and addition of IC10 of QDs could significantly improve Cu2+ induced cell toxicity with cell viability decrease up to 300 %.NAC showed remarkable protective effects with almost identical cell viability and cell morphology compared to the control,indicating the coexistence of lower toxicity of QDs could improve Cu2+ induced L02 cells toxicity,and NAC could effectively decrease QDs-Cu2 induced oxidant injury toxicity.
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Micronutrient deficiencies compromise the health and development of many school-age children worldwide. Previous research suggests that micronutrient interventions might benefit the health and development of school-age children and that multiple micronutrients might be more effective than single micronutrients. Fortification of food is a practical way to provide extra micronutrients to children. Earlier reviews of (multiple) micronutrient interventions in school-age children did not distinguish between supplementation or fortification studies. The present review includes studies that tested the impact of multiple micronutrients provided via fortification on the micronutrient status, growth, health, and cognitive development of schoolchildren. Twelve eligible studies were identified. Eleven of them tested the effects of multiple micronutrients provided via fortified food compared to unfortified food. One study compared fortification with multiple micronutrients to fortification with iodine alone. Multi-micronutrient food fortification consistently improved micronutrient status and reduced anemia prevalence. Some studies reported positive effects on morbidity, growth, and cognitive outcomes, but the overall effects on these outcomes were equivocal.
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No evidence based recommendations for micronutrient requirements during paediatric critical illness are available, other than those arising from recommended nutrient intakes (RNI) for healthy children and expert opinion.The objective of this review is to examine the available evidence from micronutrient status in critically ill children considering studies which describe 1) micronutrient levels, 2) associations between micronutrient levels and clinical outcome, and 3) impact on clinical outcome with micronutrient supplementation during PICU admission.Scoping review.Any study which used a qualitative and quantitative design considering causes and consequences of micronutrient levels or micronutrient supplementation during paediatric critical illness.NICE Healthcare Databases Advanced Search website (https://hdas.nice.org.uk/) was used as a tool for multiple searches, with a content analysis and charting of data extracted.711 records were identified, 35 were included in the review. Studies evaluated serum micronutrient status was determined on admission day in majority of patients. A content analysis identified (n = 49) initial codes, (n = 14) sub-categories and (n = 5) overarching themes during critical illness, which were identified as: i) low levels of micronutrients, ii) causes of aberrant micronutrient levels, iii) associations between micronutrients levels and outcome, iv) supplementation of micronutrients.During critical illness, micronutrients should be provided in sufficient amounts to meet reference nutrient intakes for age. Although, there is insufficient data to recommend routine supplementations of micronutrients at higher doses during critical illness, the 'absence of evidence should not imply evidence of absence', and well designed prospective studies are urgently needed to elucidate paediatric micronutrient requirements during critical illness. The absence of reliable biomarkers make it challenging to determine whether low serum levels are reflective of a true deficiency or as a result redistribution, particularly during the acute phase of critical illness. As more children continue to survive a PICU admission, particularly those with complex diseases micronutrient supplementation research should also be inclusive of the recovery phase following critical illness.
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Adequate micronutrient intake throughout life course is essential for the maintenance of health. Micronutrients are necessary for the maintenance of intermediary metabolism, play a crucial role as co-factors or co-enzymes in the activity of virtually all enzymes, and have important functions to neutralise the deleterious effects of oxidant species. Claims have been made for the benefits of micronutrient supplementation. Clinical benefit of a supplementation is obvious in those individuals who are severely depleted and at risk of complications. More recently, the concept of subclinical deficit has been developed, which essentially relies upon biochemical abnormalities the interpretation of which remains doubtful in most instances. Symptomatology related to such subclinical deficit is non specific and the potential advantages of micronutrient supplements remain marginal and largely not well-established. In contrast, provision of excess supplements to individuals who do not need them may be harmful. In the general population, a well-balanced diet supplies an adequate intake of micronutrient. Further research is needed to identify the best markers of micronutrient and antioxidant status, so that at risk patients can be identified and appropriate supplementation provided accordingly. New large-scale trials of different doses of micronutrients, based on precise outcome markers, are required to optimise intakes in different groups of patients as well as in the general population.
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Micronutrients play a crucial role in maintaining good health as they are required for various processes within the body. Every individual has different micronutrient needs depending on their metabolic condition. To achieve optimal health, these needs must be met adequately.
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Objective: In order to investigate the effect of zinc and/or micronutrients compound intervention on the physicaldevelopment in pre-school children. Methods: 480 children were divided into 3 groups: zinc group, micronutrients group, zincplus micronutrients group. During the experiment of 10 weeks, the children were supplied with zinc, micronutrients or zinc plusmicronutrients respectively. Results: The data showed that the increases of children's height and weight were significantly higherin micronutrients and zinc plus micronutrients groups than those in zinc group. Conclusion: it suggests that the supplementationof mieronutrients compound should promote children's growth and development, and that attention should be paid to the supplementation of other nutrients while zinc be supplied for children.
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Vitamins, zinc and selenium are important micronutrients that play crucial functions at the cellular and molecular level. Immune response of several different cell types can be modulated by these micronutrients. Deficiency in micronutrients has been extensively reported in HIV-1-infected individuals and further correlated with CD4+ T-cell count, HIV-1 plasma viral load, disease progression and mortality. Supplementation by micronutrients has had controversial effects. Thorough future investigations and trials are certainly needed to strategically plan evidence-based interventions. Here, we review the available data on use of micronutrients during the course of HIV-1 infection.
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In metabolism and tissue performance, micronutrients play a key role. Sufficient amount of intake is required to maintain tissue function and metabolic processes. In those people who are extremely depleted and the possibility for complications, the clinical benefits of micronutrient supplements are more advantageous in health improvement. Zinc and vitamin A supplements have contributed to lowered diarrhoea and pneumonia in children in developing countries. In slightly malnourished children, there are some indications that micronutrient supplements have cognitive influence. In several diseases, there is strong proof of the benefit of micronutrient supplements. A well-balanced diet tends to support most of the micronutrients.
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