Boron exhibits hepatoprotective effect together with antioxidant,anti-inflammatory,and anti-apoptotic pathways in rats exposed to aflatoxin B1

BackgroundAflatoxins are one of the important environmental factors that pose a risk to living organisms. On the other hand, it has been indicated in research that boron intake has beneficial effects on organisms. In this study, the effect of boron was disclosed in rats exposed to aflatoxin B1 (AFB1), which poses a toxicological risk.MethodsA total of 36 male Sprague Dawley rats were separated into 6 groups and 0.125 mg/kg bw AFB1 and 5, 10, or 20 mg/kg bw doses of boron were given orally for 21 days. End of the experiment, biochemical, molecular, and histopathological analyses were performed.ResultsAFB1 treatment increased liver enzyme activities (AST, ALT, and ALP) and malondialdehyde level; on the other hand, it caused a decrease in glutathione level, superoxide dismutase and catalase activities. In addition, the mRNA expression levels of apoptotic (Bax, Caspase-3, Caspase-8, Caspase-9, and p53) and pro-inflammatory (TNF-α and NFκB) genes increased and the mRNA expression of the anti-apoptotic gene (Bcl-2) decreased in liver tissue. Also, AFB1 treatment increased DNA damage and caused histopathological alterations in the liver tissue. Additionally, boron applications at doses of 5, 10, and 20 mg/kg bw given with AFB1 reversed these negative changes.ConclusionsAs a result, boron exhibited hepatoprotective effect together with antioxidant, anti-inflammatory, and anti-apoptotic effects against AFB1-induced liver damage.     

Synthesis of closo-Dodecaboryl Lipids and their Liposomal Formation for Boron Neutron Capture Therapy

High accumulation and selective delivery of boron into tumor tissues are the most important requirements to achieve efficient neutron capture therapy of cancers. We focused on liposomal boron delivery system to achieve a large amount of boron delivery to tumor. We succeeded in the synthesis of the double-tailed boron cluster lipids 4a–c and 5a–c, which has a B₁₂H₁₁S-moiety as a hydrophilic function, by S-alkylation of B₁₂H₁₁SH with bromoacetyl and chloroacetocarbamate derivatives of diacylglycerols. Size distribution of liposomes prepared from the boron cluster lipid 4b, dimyristoylphosphatidylcholine, polyethyleneglycol-conjugated distearoylphosphatidylethanolamine, and cholesterol was determined as 100 nm in diameter by an electrophoretic light scattering spectrophotometer. Calcein-encapsulation experiments revealed that these boronated liposomes are stable at 37 °C in fetal bovine serum solution for 24 h.     

Osservazioni Sullo Sviluppo di Lagurus Ovatus L.

Abstract

Effects of boron and molybdenum on the growth of Asparagopsis armata (Rhodophyceae, Bonnemaisoniales) in culture. - The influence of two trace-metals (boron and molybdenum) on the growth of Asparagopsis armata has been studied in culture. This alga is very tolerant of molybdenum at high concentrations, while boron rapidly becomes toxic.     

Quantitative autoradiography in boron neutron capture therapy considering the particle ranges in the samples

PurposeBoron neutron capture therapy is a cellular-scale particle therapy exploiting boron neutron capture reactions in boron compounds distributed in tumour cells. Its therapeutic effect depends on both the accumulation of boron in tumour cells and the neutron fluence. Autoradiography is used to visualise the micro-distribution of boron compounds.MethodsHere, we present an equation for the relationship between boron concentration and pit density on the solid-state nuclear track detector, taking into consideration the particle ranges in the samples. This equation is validated using liver-tissue sections and boron standard solutions. Moreover, we present a simple co-localisation system for pit and tissue-section images that requires no special equipment.ResultsThe equation reproduces the experimentally observed trends between boron concentration and pit density. This equation provides a theoretical explanation for the widely used calibration curve between pit density and boron concentration; it also provides a method to correct for differences of tissue-section thickness in quantitative autoradiography.ConclusionsUsing the equation together with this co-localisation system could improve micro-scale quantitative estimation in tissue sections.     

The effects of boron on some biochemical parameters: A review

BackgroundBoron; It is used mainly in glass and ceramics, in the defense industry, in jet and rocket fuel, as a disinfectant, and even in the agricultural sector to increase or prevent vegetation development. Its use in the health field has become more widespread when studies in recent years are reviewed. Although it has been reported that boron has essential biological effects on minerals, some enzymes, and hormones, the mechanism of these biological effects has yet to be fully elucidated. This review aims to bring a new perspective to researchers by combining the results of experimental studies in the literature on the effects of boron on some biochemical parameters.MethodsWorks of literature on boron were brought together using more than one database (WOS, PubMed, Scopus, Google Scholar). The animal, boron type and dose used in the experimental study, and biochemical parameters (glucose, urea, BUN (blood urea nitrogen), uric acid, creatinine, creatine kinase, blood lipid profile, minerals, liver function tests) were systematically compiled.ResultsIt was observed that the studies mainly focused on glucose and lipid profiles and had a lowering effect on these parameters. From a mineral point of view, the studies are mostly related to the bone matrix.ConclusionAlthough the mechanism of action of boron on biochemical parameters has not yet been clarified, it would be beneficial to examine its relationship with hormones in more depth. A good understanding and analysis of the effect of boron, which is widely used, on biochemical parameters will be beneficial in taking necessary precautions for human and environmental health.     

Synthesis and Biological Evaluation of New Enantiomers of 5-O-Carboranyl Pyrimidine Nucleosides

Abstract

The synthesis of new enantiomers of 5-o-carboranyl pyrimidine nucleosides is described. Some of these agents should be considered for boron neutron capture therapy.     

Synthesis of C-6 Pyrimidine Acyclic Nucleoside Analogs as Potential Antiviral Agents

Abstract

A number of pyrimidine acyclic nucleosides in which the acyclic moiety is attached to the C-6 position rather than N-1 of the pyrimidine ring have been prepared. This was accomplished via treatment of lithiated 2,4-dimethoxy-5,6-dimethylpyrimidine, or, 2,4-dimethoxy-6-methylpyrirnidine with 1,3-bis-(benzyloxy)-2-propanone, benzyl chloromethyl ether or oxirane, respectively, to give the corresponding key intermediates 6-[3-benzyloxy-2-[(benzyloxy)methyl]-2-hydroxypropyl]-2,4-dimethoxy-5-methylpyrimidine (2a), 6-[3-Denzyloxy-2-[(benzyloxy)methyl]-2-hydroxypropyl]-2,4-dimethoxypyrimidine(2b), 6-(2-benzyloxyethyl)-2,4-dimethoxy-5-methylpyrimidine (3), and2,4-dunethoxy-6-(3-hydroxypropyl)-5-methylpyrimidine (4a). After acidic hydrolysis, followed by debenzylation with boron trichloride these key intermediates were converted to the target C-6 pyrimidine acyclic derivatives. Compounds 6–8b, 11–13, 15, 16, 20, 22, 26, and 29–32 were evaluated for activity against herpes viruses and human immunodeficiency virus. None of the compounds were active against the viruses nor were they cytotoxic at the highest concentration tested.     

Effect of supplementation of different boron and copper levels to layer diets on performance,egg yolk and plasma cholesterol

ProcedureThis study was conducted to determine the effects of supplementation of different levels boron and copper on performance, lipids in yolk and plasma contains in layer diets. In this trial a total of 320 layer chicken (26 weeks old age) was randomly distributed in 16 experimental groups. In each experiment group were consist at 5 replicates, and in each replicates there were 4 birds. During the 16 weeks experiment period, birds were fed with 16 experimental diets. Experimental diets were consisting of all possible combination of 4 levels of added boron (0, 60, 120 and 240 mg/kg) and 4 levels of added copper (0, 75, 150 and 300 mg/kg) to the basal ration.ResultsEffect of treatments on body weight change and plasma glucose levels were not significant. However, added boron and copper had a significant effect on plasma high-density lipoprotein cholesterol fraction. While added boron had a significant adverse effect on performance parameters, added copper had a significant positive effect on the same parameters. Yolk lipid contents were increased by addition of boron to the ration. However, yolk lipid contents were decreased by addition of copper to the ration. Plasma lipid contents were also decreased by addition of copper and boron in the ration.ConclusionResults of the present study showed that laying hens from 26 to 42 weeks of age should be fed with 60 mg/kg boron and 150 mg/kg copper supplementation in the diet.     

Investigation of some impurity profiles by (n,α) reactions

To investigate some impurity profiles by (n,α) reactions for destructive and nondestructive analysis, two experimental facilities on a horizontal channel of the well-moderated research reactor have been developed. In accordance with an α-particle registration geometry two different measurement techniques based on using a surfacebarrier Si(Au) detector and a counting ionization chamber have been used. The determination limit of boron is ofn x 10¹⁶ cm^-3 or (1 /dv 5) x 10^-5 % with a depth resolution of ±0.03 Μm in semiconductors. A solid-state nuclear track detector (SSNTD) has also been used to determine the boron surface and deep distributions in semiconductors, plants, and other materials.     

Intramedullary implants coated with cubic boron nitride enhance bone fracture healing in a rat model

BackgroundBoron nitride is a biocompatible and an osteo-inductive material for orthopedic applications. The aim of this study was to evaluate the effects of two different allotrope boron nitride coated implants, cubic boron nitride and hexagonal boron nitride, on fracture healing.MethodsIn this experimental study, a total of 24 rats were divided into three groups. Group A was the control group with Kirschner wire without coating, while the wires were coated dominantly by cubic boron nitride in Group B and hexagonal boron nitride in Group C. Then a mid-third femoral fracture was created. The fracture healing was examined in terms of new bone formation with micro-CT analysis and histopathological examination, quantitative measurement of bone turnover metabolites and scintigraphic examination of osteoblastic activity on 28th day post fracture.ResultsMicro-CT measurement results revealed a statistically significant increase in bone volume/tissue volume ratio and bone surface values in group B compared to group A. Cortex diameter and osteoblast counts were statistically higher in group B compared to group A. Inflammatory response was increased in group C compared to groups A and B. Biochemical test results showed significantly increased alkaline phosphatase levels and decreased osteocalcin levels in group B compared to group A. The increase in serum phosphorus and decrease in serum calcium levels was statistically significant in group C compared to Group A.ConclusionBoth types of boron nitride coating had superior fracture healing features compared to control group. Therefore, c-BN coating can accelerate the fracture healing and could lead to shorten of union time.     

Pivotal role of boron supplementation on bone health: A narrative review

BackgroundBoron is a trace element that plays an important role in numerous biological functions, including calcium metabolism, growth and maintenance of bone tissue. However, there are still no precise indications regarding a possible role of boron supplementation, and its amount of supplementation, to maintain bone health. So the aim of this narrative review was to consider the state of the art on the effectiveness of boron supplementation (alone or with other micronutrients) on growth and maintenance of bone in humans through control of calcium, vitamin D and sex steroid hormone metabolism in order to suggest a daily dosage of boron supplementation.Main findingsThis review included 11 eligible studies: 7 regarding the supplementation with boron alone and 4 regarding supplementation with boron and other nutrients. Despite the number of studies considered being low, the number of subjects studied is high (594) and the results are interesting.ConclusionsThe studies considered in this narrative review have evaluated the positive effectiveness on bone, in humans, through control of calcium, vitamin D and sex steroid hormone metabolism, considering a dietary supplementation of 3 mg/day of boron (alone or with other nutrients); this supplementation is demonstrably useful to support bone health (in order to prevent and maintain adequate bone mineral density), also considering the daily dose of 3 mg is much lower than the Upper Level indicated by EFSA in the daily dose of 10 mg.     

A new Class of Drugs for BNCT? Borylated derivatives of ferrocenium compounds in animal experiments

A new class of drugs, borylated derivatives of ferrocenium compounds, which show a comparatively facile synthesis is investigated on their boron neutron capture accumulation. Investigations focused on the fast and effective testing of 12 ferrocene derivatives with tetracoordinated boron atoms, which should accumulate in rodent tumors. The macroscopic studies on time-dependent boron distributions and boron concentrations in mice were carried out by inductively coupled plasma-atomic emission spectrometry, inductively coupled plasma-mass spectrometry, and quantitative neutron capture radiography. The determination of boron concentrations after injection of 2b showed high boron contents in spleen, liver, kidneys, less in lung and muscle, and poor in integral blood, blood plasma, tumor, and brain. It is interesting to note that 2b penetrates the blood-brain barrier which may be advantageous in the treatment of astrocytomas and glioblastomas.     

Evaluation of the effect of boron derivatives on cardiac differentiation of mouse pluripotent stem cells

BackgroundThe heart is one of the first organs to form during embryonic development and has a very important place. So much that the formation of a functional heart is completed on the 55th day of human development and the 15th day of mouse development. Myocardial, endocardial and epicardial cells, which are derived from the mesoderm layer, are the cells that form the basis of the heart. Cardiac development, like other embryonic developments, is tightly controlled and regulated by various signaling pathways. The WNT signaling pathway is the most studied of these signaling pathways and the one with the clearest relationship with heart development. It is known that boron compounds and the Wnt/β-catenin pathway are highly correlated. Therefore, this study aimed to investigate the role of boron compounds in heart development as well as its effect on pluripotency of mouse embryonic stem cells for the first time in the literature.MethodsToxicity of boron compounds was evaluated by using MTS analysis and obtained results were supported by morphological pictures, Trypan Blue staining and Annexin V staining. Additionally, the possible boron-related change in pluripotency of embryonic stem cells were analyzed with alkaline phosphatase activity and immunocytochemical staining of Oct4 protein as well as gene expression levels of pluripotency related OCT4, SOX2 and KLF4 genes. The alterations in the embryonic body formation capacity of mouse embryonic stem cells due to the application boron derivatives were also evaluated. Three linage differentiation was conducted to clarify the real impact of boron compounds on embryonic development. Lastly, cardiac differentiation of mESCs was investigated by using morphological pictures, cytosolic calcium measurement, gene expression and immunocytochemical analysis of cardiac differentiation related genes and in the presence of boron compounds.ResultsObtained results show that boron treatment maintains the pluripotency of embryonic stem cells at non-toxic concentrations. Additionally, endodermal, and mesodermal fate was found to be triggered after boron treatment. Also, initiation of cardiomyocyte differentiation by boron derivative treatments caused an increased gene expression levels of cardiac differentiation related TNNT2, Nkx2.5 and ISL-1 gene expression levels.ConclusionThis study indicates that boron application, which is responsible for maintaining pluripotency of mESCs, can be used for increased cardiomyocyte differentiation of mESCs.     

Synthesis of Racemic 5-Substituted 1-(2,3-Dihydroxypropyl)-6-azauracils and Their Isosteric Isomers

Abstract

Acyclic nucleoside analogues of antiviral DHPA and HPMPA have been prepared. Coupling of silylated 6-azauracils with benzyl glycidyl ether and stannic chloride followed by the deprotection with boron trichloride gave 1-(2,3-dihydroxypropyl)-6-azauracils (3) in good overall yields. Reaction of silylated 6-azauracil and epichlorohydrin with or without catalytic stannic chloride afforded 1-(2-chloro-3-hydroxypropyl)-6-azauracil (4a) and 1-(3-chloro-2-hydroxypropyl)-6-azauracil (6a) respectively. Coupling of silylated 6-azaisocytosine under the same reaction conditions provided 1-(2,3-dihydroxypropyl)-6-azaisocytosine (9) and 1-(2-chloro-3-hydroxypropyl)-6-azaisocytosine (10) respectively. None of the compounds exhibited significant antiviral activity against herpes simplex viruses.     

Benchmarking of ONIOM method for the study of NH<Subscript>3</Subscript> dissociation at open ends of BNNTs

The reliability of ONIOM approach have been examined in calculations of adsorption energies, transition structures, change of HOMO-LUMO energy gaps and equilibrium geometries of the interaction between NH₃ and N-enriched (A) or B-enriched (B) open ended boron nitride nanotubes. To these ends, four models of the A or B, with different inner and outer layers have been studied. In addition, various low-levels including, AM1, PM3, MNDO and UFF have been examined, applying B3LYP/6-31 G* in all high-levels. It was shown, that in the case of A, (choosing two atom layers of the tube open-end as inner layer) the results of ONIOM approach are in best agreement with those of the pure density functional theory (DFT) calculations, while their results significantly differ from those of DFT in the case of B in same conditions. All above and population analysis demonstrate that the ONIOM may be a reliable scheme in the study of weak interactions while it is a controversial approach and should be applied cautiously in the case of strong interactions. We also probed the effect of tube length and diameter on the consistency between ONIOM and DFT results, showing that this consistency is independent of the mentioned parameters.     

Novel Lewis Acid-Catalyzed Rearrangement of a Sugar-Base Hybrid to Afford an Anhydronucleoside

Abstract

Treatment of the sugar-base hybrid 9 with boron trichloride at low temperature for 40 h affords the 6,3′-anhydro-2′-deoxyuridine 10 in 40% yield (80% based on recovered 9) via a novel structural rearrangement.     

Boron Containing Pyrimidines,Nucleosides, and Oligonucleotides for Neutron Capture Therapy

Abstract

The synthesis and encouraging biological findings with boron-containing nucleosides, such as 5-dihydroxyboryl-2′-deoxyuridine, which could be used for boron neutron capture therapy (BNCT) for the treatment of various malignancies, has provided momentum to synthesize several boron containing nucleosides and oligomers. BNCT is based on the property of the non-radioactive boron-10 isotope to capture low energy neutrons, thereby producing a localized cell-destroying nuclear reaction. Thus, irradiation of tumor cells with neutrons, following incorporation of the boronated nucleoside, would result in the destruction of tumor tissue only. Intracellular phosphorylation by nucleoside kinases, and/or incorporation into the cancer cell DNA as a false nucleotide precursor, followed by irradiation by neutrons, would lead primarily to tumor cell death. The synthetic and biological approaches for boronated pyrimidines, nucleosides, and oligonucleotides for BNCT are reviewed.     

Combined effect of boron and salinity on water transport: The role of aquaporins

Boron toxicity is an important disorder that can limit plant growth on soils of arid and semi arid environments throughout the world. Although there are several reports about the combined effect of salinity and boron toxicity on plant growth and yield, there is no consensus about the experimental results. A general antagonistic relationship between boron excess and salinity has been observed, however the mechanisms for this interaction is not clear and several options can be discussed. In addition, there is no information, concerning the interaction between boron toxicity and salinity with respect to water transport and aquaporins function in the plants. We recently documented in the highly boron- and salt-tolerant the ecotype of Zea mays L. amylacea from Lluta valley in Northern Chile that under salt stress, the activity of specific membrane components can be influenced directly by boron, regulating the water uptake and water transport through the functions of certain aquaporin isoforms.Key words: aquaporins, boron, salinity, water relations, Zea maysHigh concentrations of boron are often associated to saline soils in semi arid and/or arid climates and frequently crops are exposed to both stresses simultaneously.¹ As there is no a unique plant response to combination of salinity and boron toxicity, several mechanisms has been proposed to explain the experimental results. Some reports showed no additive effects of boron and salinity on shoot weight of different cultivars suggesting independent of the interaction.^2–5 However, additive effects^6–9 have been also proposed and the interaction of boron and salinity declined the rate of germination and limited growth in maize and sorghum plants.¹⁰ No explanation is currently available for these contradictory observations. Recently, the Abbot method has been applied to characterize the combined effect of boron and salinity at toxic levels in pepper plants, observing mainly an antagonistic relationship regarding growth and yield.¹¹ Antagonism between salinity and boron may be the result of decreased toxicity of boron in the presence of NaCl, reduced toxicity of NaCl in the presence of boron, or both together. Letey et al.,¹² have reported that increased soil salinity may also reduce boron movement to the broccoli plants and hence result in a reduction of boron toxicity symptoms. Reduction of boron accumulation in leaves in the presence of salinity has been also reported for melon,⁵ tomato⁸ jack pine¹³ and grapesvines¹⁴ and could be the result of the reduced rates of transpiration in plants where boron is transported via xylem as consequence of the osmotic effect of the salt. On the other hand, it has been observed that concentration of Na⁺ in leaves decreased with increasing addition of boron to the soil, probably due to the inhibition in root growth and reduction in root density caused by the boron treatment.¹⁵ Grieve and Poss⁷ found in wheat plants that the Cl⁻ content in the leaves was reduced when boron was increased. Similar results were reported in pepper plants suggesting that boron could reduce Cl⁻ toxicity.¹¹ Also, in our recent report although a nutrient imbalance resulted from the effect of salinity or boron alone, a general optimisation was observed when both treatments were applied together.¹⁶Under saline conditions, an optimal water balance is important in order to maintain the plant homeostasis and aquaporins may be one of the mechanisms involved under environmental and developmental changes.^17–19 However, there is no information concerning plant water uptake and transport in response to combined excess boron and salinity.It has been reported that, at high external B concentrations, considerable B transport occurs through the plasma membrane aquaporins, and a specific membrane intrinsic protein (MIP) has been described.²⁰ Thus boron uptake across the plasma membrane, by permeation through the lipid membrane and aquaporins, may be greatly influenced by the plant tolerance to salinity, through the associated changes in root hydraulic conductivity. Wimmer et al.,²¹ showed that salinity could interact with boron toxicity by a combined effect on boron and water uptake. In addition, we reported that the reduction of aquaporin functionality in NaCl-exposed plants could induce the reduction of plant boron concentration, producing a beneficial effect.²²Recently, we showed in a tolerant ecotype of maize a different pattern for PIP1 and PIP2 protein content under the application of excess of boron in combination with salinity, suggesting a differential aquaporin response in this cultivar and pointed out the complexity of the interaction.¹⁶ These results were in consonance with the previous observation that different aquaporin isoforms may represent a response to environmental changes.^18,19,²³ Thus, we concluded that the activity of specific membrane components can be influenced by boron under salt stress regulating the functions of certain aquaporin isoforms as possible components of the salinity tolerance mechanism. However, although a fine water transport control through the aquaporins could be necessary in order to reduce the accumulation of toxic boron levels in the tissues, the contribution of each isoform to water transport through the plasma membrane under boron-salinity combination must be elucidated.