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Effects of Magnesium, Calcium, and Aluminum Chelation on Fluoroquinolone Absorption Rate and Bioavailability: A Computational Study.

ABSTRACT: Fluoroquinolones (FQs) are a widespread class of broad-spectrum antibiotics prescribed as a first line of defense, and, in some cases, as the only treatment against bacterial infection. However, when administered orally, reduced absorption and bioavailability can occur due to chelation in the gastrointestinal tract (GIT) with multivalent metal cations acquired from diet, coadministered compounds (sucralfate, didanosine), or drug formulation. Predicting the extent to which this interaction reduces in vivo antibiotic absorption and systemic exposure remains desirable yet challenging. In this study, we focus on quinolone interactions with magnesium, calcium and aluminum as found in dietary supplements, antacids (Maalox) orally administered therapies (sucralfate, didanosine). The effect of FQ-metal complexation on absorption rate was investigated through a combined molecular and pharmacokinetic (PK) modeling study. Quantum mechanical calculations elucidated FQ-metal binding energies, which were leveraged to predict the magnitude of reduced bioavailability via a quantitative structure-property relationship (QSPR). This work will help inform clinical FQ formulation design, alert to possible dietary effects, and shed light on drug-drug interactions resulting from coadministration at an earlier stage in the drug development pipeline.

SUBMITTER: Walden DM

PROVIDER: S-EPMC8143323 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Enhanced ultraviolet absorption in graphene by aluminum and magnesium hole-arrays.

Project description:Optoelectronic devices in the UV range have many applications including deep-UV communications, UV photodetectors, UV spectroscopy, etc. Graphene has unique exciton resonances, that have demonstrated large photosensitivity across the UV spectrum. Enhancing UV absorption in graphene has the potential to boost the performance of the various opto-electronic devices. Here we report numerical study of UV absorption in graphene on aluminum and magnesium hole-arrays. The absorption in a single-layer graphene on aluminum and magnesium hole-arrays reached a maximum value of 28% and 30% respectively, and the absorption peak is tunable from the UV to the visible range. The proposed graphene hybrid structure does not require graphene to be sandwiched between different material layers and thus is easy to fabricate and allows graphene to interact with its surroundings.

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Early osteoimmunomodulatory effects of magnesium-calcium-zinc alloys.

Project description:Today, substantial attention is given to biomaterial strategies for bone regeneration, and among them, there is a growing interest in using immunomodulatory biomaterials. The ability of a biomaterial to induce neo vascularization and macrophage polarization is a major factor in defining its success. Magnesium (Mg)-based degradable alloys have attracted significant attention for bone regeneration owing to their biodegradability and potential for avoiding secondary removal surgeries. However, there is insufficient evidence in the literature regarding the early inflammatory responses to these alloys in vivo. In this study, we investigated the early body responses to Mg-0.45wt%Zn-0.45wt%Ca pin-shaped alloy (known as ZX00 alloy) in rat femora 2, 5, and 10 days after implantation. We used 3D micro computed tomography (µCT), histological, immunohistochemical, histomorphometrical, and small angle X-ray scattering (SAXS) analyses to study new bone formation, early macrophage polarization, neo vascularization, and bone quality at the implant bone interface. The expression of macrophage type 2 biological markers increased significantly after 10 days of Mg alloy implantation, indicating its potential in stimulating macrophage polarization. Our biomineralization results using µCT as well as histological stained sections did not indicate any statistically significant differences between different time points for both groups. The activity of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx 2) biological markers decreased significantly for Mg group, indicating less osteoblast activity. Generally, our results supported the potential of ZX00 alloy to enhance the expression of macrophage polarization in vivo; however, we could not observe any statistically significant changes regarding biomineralization.

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Calcium Absorption from Food Products: Food Matrix Effects.

Project description:This article reviews physicochemical aspects of calcium absorption from foods. Notable differences are observed between different food products in relation to calcium absorption, which range from <10% to >50% of calcium in the foods. These differences can be related to the interactions of calcium with other food components in the food matrix, which are affected by various factors, including fermentation, and how these are affected by the conditions encountered in the gastrointestinal tract. Calcium absorption in the intestine requires calcium to be in an ionized form. The low pH in the stomach is critical for solubilization and ionization of calcium salts present in foods, although calcium oxalate complexes remain insoluble and thus poorly absorbable. In addition, the rate of gastric transit can strongly affect fractional absorption of calcium and a phased release of calcium into the intestine, resulting in higher absorption levels. Dairy products are the main natural sources of dietary calcium in many diets worldwide, which is attributable to their ability to provide high levels of absorbable calcium in a single serving. For calcium from other food products, lower levels of absorbable calcium can limit contributions to bodily calcium requirements.

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Gene expression profiling in soybean under aluminum stress: mechanisms of magnesium amelioration of aluminum toxicity

Project description:Gene expression profiling in soybean under aluminum stress: mechanisms of magnesium amelioration of aluminum toxicity at gene expression level. Micro-molar concentrations of magnesium in culture solution has been shown to ameliorate Al toxicity in soybean and other leguminous species. Different theories have been proposed to explain the chemical mechanisms of how the two ions interact to neutralize the toxic effect of aluminum in the plant root system. To understand the molecular mechanisms of the phenomenon at the gene expression level in soybean, we undertook a comparative transcriptome analysis in Al-tolerant and Al-sensitive genotypes treated with aluminum alone or aluminum plus magnesium using DNA microarrays. The results revealed magnesium enhances Al-tolerance level in the Al-tolerant genotype by down-regulating genes commonly induced in response to Al toxicity. We hypothesized that the magnesium-mediated alleviation of Al toxicity in the Al-tolerant genotype emanates from reduction in energy expenditure of gene expression induced in response to Al stress. Conversely, magnesium appears to ameliorate Al toxicity in the sensitive genotype by dual mechanisms of increasing the expression level of several genes involved in Al-tolerance and decreasing the expression level of most genes. Keywords: Soybean, aluminum toxicity, magnesium, transcriptome

2010-10-04 | GSE18518 | GEO

Predicting and Testing Bioavailability of Magnesium Supplements.

Project description:Despite the presumption of the beneficial effects of magnesium supplementation, little is known about the pharmacokinetics of different magnesium formulations. We aimed to investigate the value of two in vitro approaches to predict bioavailability of magnesium and to validate this in subsequent in vivo testing. In vitro assessment of 15 commercially available magnesium formulations was performed by means of a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) and by dissolution tests. Two magnesium formulations with contrasting bioavailability prediction from both in vitro tests (best vs. worst) were selected for in vivo testing in 30 subjects. In vivo bioavailability was compared following one acute ingestion by monitoring blood magnesium concentrations up to 6 h following intake. The in vitro tests showed a very wide variation in absorption and dissolution of the 15 magnesium products. In the in vivo testing, a significant different serum magnesium absorption profile was found up to 4 h following supplement ingestion for the two supplements with opposing in vitro test results. Moreover, maximal serum magnesium increase and total area under the curve were significantly different for both supplements (+6.2% vs. +4.6% and 6.87 vs. 0.31 mM.min, respectively). Collectively, poor bioaccessibility and bioavailability in the SHIME model clearly translated into poor dissolution and poor bioavailability in vivo. This provides a valid methodology for the prediction of in vivo bioavailability and effectiveness of micronutrients by specific in vitro approaches.

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Gene expression profiling in soybean under aluminum stress: mechanisms of magnesium amelioration of aluminum toxicity

2010-10-04 | E-GEOD-18518 | biostudies-arrayexpress

Calcium and Magnesium responses in Brassica rapa

Project description:A mapping population of Brassica rapa (BraIRRI, IMB211xR500) was grown under four external calcium and magnesium concentrations in controlled conditions. RNA was extracted and hybridised to the Affymetrix Brassica Exon 1.0 ST array. The aim of the experiment was to identify cis- and trans- expression quantitative trait loci. In total 279 samples were analysed. The parents of the mapping population were grown at all four treatment levels (LL, HL, LH, HH) with three biological replicates per treatment, plus 12 technical replicates (n=36). A 2x2 combination of external calcium and magnesium concentrations were imposed to give four treatments (LL, HL, LH, HH) as follows: the high (H) concentrations were 3.5 g L-1 (24 mM) CaCl2 and 3.04 g L-1 (15 mM) MgCl2 and the low (L) concentrations were 0.44 g L-1 (3 mM) CaCl2 and 0.2 g L-1 (1 mM) MgCl2 For the mapping population (total = 85 lines), 85 lines were analysed for the LL treatment, 81 lines were analysed for the LH treatment and 65 lines were analysed for the HL treatment. Twelve technical replicates were also analysed.

2014-05-21 | E-GEOD-44185 | biostudies-arrayexpress

Calcium and Magnesium responses in Brassica rapa

2014-05-21 | GSE44185 | GEO

Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Represents an Oral Formulation of Resveratrol With Better Gastric Absorption and Bioavailability Respect to Pure Resveratrol.

Project description:Resveratrol attracts great interest because of the plethora of in vitro effects at the micromolar concentration range. Unfortunately, these effects are difficult to establish in vivo, due to the low concentration of resveratrol reached. This discrepancy is due to the molecules low solubility in water that favors the propensity for an intestinal absorption rather than in the gastric compartment. To address these challenges, we developed a Solid Dispersion of Resveratrol Supported by Magnesium Di Hydroxide formulation (Resv@MDH). This formulation displays increased water solubility and better bioavailability relative to pure resveratrol in the rabbit animal model. In our study, we evaluated the pharmacokinetics profile of resveratrol in six healthy human subjects following 180 mg of oral resveratrol administration, derived from Resv@MDH or pure resveratrol. Free resveratrol was evaluated in the whole blood sample by using HPLC - MS/MS. In comparison with pure resveratrol that displays an increase of the maximum plasma concentration, Cmax at about 90 min and 2 μM, Resv@MDH displays an earlier peak of resveratrol concentration with an increase of Cmax at about 30 min and 6 μM. The different kinetics suggest a main gastric route for resveratrol absorption from Resv@MDH, where, because of its improved dissolution rate, there seems to be a higher propensity for an acidic environment, as opposed to that with pure resveratrol. This conclusion is also supported by the numerical simulation analysis, which considers the principal steps during the oral route administration. Moreover, there is a 2-fold increase in the amount of free resveratrol with respect to pure resveratrol confirming a better bioavailability observed in the animal model. The characteristic feature of the pharmacokinetic profile of Resv@MDH implies that the beneficial properties of resveratrol in human health should be capitalized on it.

| S-EPMC8377765 | biostudies-literature

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