Use Of Methionine Research Articles

Plasma Methionine and Clinical Severity in Nitrous Oxide Consumption.

In the last few years, there has been an increase in the recreational use of nitrous oxide (N2O), which can lead to neurological symptoms such as sensory or motor disorders. The literature links these symptoms to a functional inactivation of vitamin B12 by oxidation of its cobalt ion, which prevents the vitamin B12 from acting as a cofactor for methionine synthase. Thus, demyelination related to methionine deficiency could be responsible for the neurological disorders associated with N2O consumption, including the combined sclerosis of the spinal cord. We aimed to study the correlation between the plasma methionine levels and clinical severity observed in N2O users. We retrospectively collected clinical and biological data from 93 patients who chronically consumed N2O. The patients were divided into four groups based of the severity of their clinical symptoms (based on their Peripheral Neuropathy Disability (PND) score). The plasma amino acids measurement, including methionine, were performed systematically by liquid chromatography coupled with mass spectrometry. Plasma methionine is significantly correlated with the clinical severity (Spearman coefficient: −0.42; p-value < 10−5), however, the average methionine level in the four groups is within the physiological values (N: 16−23 µmol/L). There is a significant inverse correlation between plasma methionine and homocysteine (Spearman coefficient: −0.57; p-value < 10−9), which confirms the action of nitrous oxide on the methionine synthase. A decrease in plasma methionine cannot be imputed as the only mechanism involved in the pathophysiology of the neurological disorders in nitrous oxide consumption. In addition, there are few therapeutic indications for the use of methionine. Thus, we should be careful concerning the potential use of methionine in nitrous oxide consumption. As a consequence, other pathophysiological mechanisms probably need to be identified in order to find potential therapeutic targets.

Reversion of methionine addiction of osteosarcoma cells to methionine independence results in loss of malignancy, modulation of the epithelial-mesenchymal phenotype and alteration of histone-H3 lysine-methylation.

Methionine addiction, a fundamental and general hallmark of cancer, known as the Hoffman Effect, is due to altered use of methionine for increased and aberrant transmethylation reactions. However, the linkage of methionine addiction and malignancy of cancer cells is incompletely understood. An isogenic pair of methionine-addicted parental osteosarcoma cells and their rare methionine-independent revertant cells enabled us to compare them for malignancy, their epithelial-mesenchymal phenotype, and pattern of histone-H3 lysine-methylation. Methionine-independent revertant 143B osteosarcoma cells (143B-R) were selected from methionine-addicted parental cells (143B-P) by their chronic growth in low-methionine culture medium for 4 passages, which was depleted of methionine by recombinant methioninase (rMETase). Cell-migration capacity was compared with a wound-healing assay and invasion capability was compared with a transwell assay in 143B-P and 143B-R cells in vitro. Tumor growth and metastatic potential were compared after orthotopic cell-injection into the tibia bone of nude mice in vivo. Epithelial-mesenchymal phenotypic expression and the status of H3 lysine-methylation were determined with western immunoblotting. 143B-P cells had an IC50 of 0.20 U/ml and 143B-R cells had an IC50 of 0.68 U/ml for treatment with rMETase, demonstrating that 143B-R cells had regained the ability to grow in low methionine conditions. 143B-R cells had reduced cell migration and invasion capability in vitro, formed much smaller tumors than 143B-P cells and lost metastatic potential in vivo, indicating loss of malignancy in 143B-R cells. 143B-R cells showed gain of the epithelial marker, ZO-1 and loss of mesenchymal markers, vimentin, Snail, and Slug and, an increase of histone H3K9me3 and H3K27me3 methylation and a decrease of H3K4me3, H3K36me3, and H3K79me3 methylation, along with their loss of malignancy. These results suggest that shifting the balance in histone methylases might be a way to decrease the malignant potential of cells. The present results demonstrate the rationale to target methionine addiction for improved sarcoma therapy.

Effect of guanidinoacetic acid supplementation on nitrogen retention and methionine methyl group flux in growing steers fed corn-based diets.

Six ruminally cannulated Holstein steers (256 ± 14 kg) were used in a 6 × 6 Latin square design to assess effects of guanidinoacetic acid (GAA) supplementation on N retention and methionine (Met) methyl group flux in growing cattle fed corn-based diets. Factorial treatments were two levels of Met (0 or 5 g/d) and three levels of GAA (0, 7.5, or 15 g/d) delivered by continuous abomasal infusion. Periods were 10 d in length and included 6 d of treatment adaptation, 3 d for total fecal and urine collections, and 1 d for blood sampling and flux measurements. Urinary N linearly increased (P < 0.01) with GAA supplementation and decreased (P < 0.05) with Met supplementation. Fecal N excretion was unaffected (P ≥ 0.42) by treatment. Retained N was not affected by GAA supplementation, but it was increased (P < 0.01) by Met supplementation. Use of methionine for transmethylation reactions, as well remethylation of homocysteine, was not affected by GAA supplementation when Met was not supplemented, but tended to be linearly increased by GAA supplementation when Met was supplemented (GAA-linear × Met interaction; P = 0.07), with the increases matching the amount of GAA provided. This response suggests that methylation reactions for compounds other than GAA were reduced by GAA supplementation when Met supply was deficient. Plasma concentrations and urinary excretion of creatine increased linearly (P = 0.03 and P = 0.06, respectively) when GAA was supplemented. There was a linear increase (P < 0.01) in urinary GAA excretion with GAA supplementation. Neither plasma concentration nor urinary excretion of creatinine was affected (P ≥ 0.17) by treatment. No treatment differences (P ≥ 0.13) were observed for plasma haptoglobin concentrations. Plasma urea-N linearly increased (P < 0.05) with GAA supplementation. Concentrations of Met and taurine increased (P < 0.05) when Met was supplemented. Plasma arginine was greatest at the intermediate level of supplemental GAA (quadratic, P < 0.05). The increase in N retention when Met was supplemented demonstrates Met was limiting in the corn-based diet. Supplementation of GAA alone or with Met as a methyl donor did not increase N retention in growing steers, perhaps because creatine production was favored over protein deposition as a use for Met.

The effects of metakaolin on mortar compressive strenght a case study of mortar estrich plester

Mortar as a binding material in couple and stucco work has long been known ranging from very simple technologies to more advanced ones. Nowadays mortar technology has developed so rapidly along with the advancement of construction technology. The development of technology in the construction industry has resulted in better product and system innovations so that they are more competitive and applicable. The demands of increasingly complex needs also need to be responded to wisely and made as hopes and opportunities in business development. Ready-mix mortar is perfect for all kinds of work such as normal masonry, light brick, stucco, ceramics, and floor coating. While from the mechanical properties, the compressive strength of the mortar can meet requirements of standard specifications according to the purpose of its use. Ready-made Dry Plaster Mortar is a mixture of fine aggregate with binding material and various additives. The purpose of using additives is to improve the properties of ready-mix plaster dry mortar. One of the additives used is metakaolin. This study aims to determine the effect of metakaolin on compressive strength and cost efficiency of plastering (mortar). The compressive pressure test object measures 50 mm x 50 mm x 50 mm. Compressive strength testing is carried out at the time when the mortar is 7, 14 and 28 days old. The study was conducted with variations in the use of Metakaolin in ostrich mortar plaster products, namely 0%, 5%, 7.5%, 10%, The results showed that a mixture of ready-made plaster dry mortar with the use of methionine 10% of the weight of cement was able to provide a ready-made dry plaster mortar that meet the requirements in ASTM C 91, Standard specification for masonry cement.

Production of process flavorings from methionine, thiamine with d-xylose or dextrose by direct extrusion: Physical properties and volatile profiles.

The conventional method to produce process flavoring is non-continuous, time consuming, and generates a high volume of effluent. This research aimed to evaluate the use of methionine, thiamine, and reducing sugars to develop process flavorings by direct extrusion, as a potential alternative to the conventional method. The mixed substrates consisted of methionine: d-xylose (MX), methionine: dextrose (MD), thiamine: d-xylose (TX), and thiamine: dextrose (TD) at 80:20 w/w. Three barrel temperatures of the extruder were controlled at 65, 80, and 50°C, respectively, a screw speed of 30rpm and feed rate at 3 kg/hr. Appearance, pH, odor, and taste description of the product from each mixture were determined. Volatile compounds, possibly occurred from the Maillard reaction during the extrusion were analyzed by gas chromatography-mass spectrometry. The products exhibited different levels of meaty odor and bitter taste. Those obtained from MD showed the highest L* (lightness, 85.37) and frequency for just-about-right in terms of taste (33.33%) and odor (60.00%). Products from MX and MD presented the highest frequency for intense taste, and higher frequency for color compared to TX and TD. More volatile compounds were detected from the use of methionine than from thiamine. The key meaty odor compounds such as dimethyl disulfide, dimethyl trisulfide, methional, and methanethiol were found in the samples from MX and MD, while only dimethyl disulfide was detected in the mixture of TX and TD. Finally, the results demonstrated that direct extrusion reaction from methionine and d-xylose or dextrose is a highly efficient method to produce meaty process flavorings. PRACTICAL APPLICATION: The manuscript describes the production of process flavorings that exhibited meaty flavors by extrusion process. Physical properties, volatile profiles, and sensory evaluation of the products from methionine, thiamine, d-xylose, and glucose were evaluated. The extruded products from methionine and dextrose exhibited acceptable color, taste, and odor and presented many volatiles compounds contributing to meaty flavors. The results revealed the high potential to use a direct extrusion process with very low effluent, compared to the conventional method, to produce meaty flavors for industrial application.

Optimization of methionine in inhalable High-dose Spray-dried amorphous composite particles using response surface Method, infrared and low frequency Raman spectroscopy

The influence of amino acids, other than leucine, in improving aerosolization of inhalable powders has not been widely explored. This detailed study focused on the use of methionine, another promising endogenous amino acid, in high dose spray-dried co-amorphous powders by investigating the influence of methionine proportion (0 – 20% w/w), and feed concentration (0.2 – 0.8% w/v) on aerosolization of kanamycin, a model drug, using a design of experiment approach. Low frequency Raman spectroscopy was used to assess the stability of the powders stored at 25 °C/53% relative humidity over 28 days. An increase in concentration of methionine was associated with an increase in fine particle fraction (FPF), with the highest FPF of 84% being achieved at 20% w/w and 0.2% w/v feed concentration. With an increase in feed concentration, both yield and particle size increased for all formulations; the FPF did not change except for kanamycin only formulation in which it decreased. During storage at high humidity, similar aerosolization stabilities were offered by different proportions of methionine although methionine crystallized out in all formulations. Furthermore, the crystallization was accompanied by surface enrichment of methionine on the particles. This study suggests that there is a direct relationship between methionine content and aerosolization for kanamycin-methionine amorphous matrices but feed concentration has little effect. In addition, methionine proportion has no effect on physical stability of such matrices at high humidity.

One-carbon metabolism in children with marasmus and kwashiorkor.

SummaryBackgroundKwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor's disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children.MethodsBlood was collected from children aged 12–60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups.FindingsTwelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P < 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P < 0·0001 & 115 (± 50) P < 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor.InterpretationKwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome's pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation.FundingThe Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS.

Reversion from Methionine Addiction to Methionine Independence Results in Loss of Tumorigenic Potential of Highly-malignant Lung-cancer Cells.

Methionine addiction, a fundamental and general hallmark of cancer, is due to the excess use of methionine for transmethylation, and is described as the Hoffman-effect. Methionine-addicted cancer cells can revert at low frequency to methionine independence when selected under methionine-restriction. We report here that highly-malignant methionine-addicted H460 human lung-cancer cells, when selected for methionine independence, have greatly-reduced tumorigenic potential. Methionine-addicted H460 parental cancer cells and methionine-independent revertant H460-R1 cells were injected in nude mice subcutaneously. When the parental H460 methionine-addicted cells were injected in nude mice at 2.5×105, 1×105 and 5×104, the cells could form tumors. In contrast, the H460-R1 methionine-independent revertant cells could not form tumors when the above-listed cell numbers were injected in nude mice. There is a tight linkage between methionine addiction and malignancy.

Novel radiopharmaceutical (Technetium-99m)-(DOTA-NHS-ester)-Methionine as a SPECT-CT tumor imaging agent

Breast cancer is the most common type of cancer in women worldwide. There have been many efforts for early breast cancer detection and among them molecular imaging have been extremely of high importance. Single-photon emission computed tomography (SPECT/CT) is a kind of imaging technique able to reveal crucial information with using radiopharmaceuticals.In this study, Technetium-99m-(DOTA-NHS-ester)-Methionine radiopharmaceutical was synthesized. Between 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DOTA-HNS ester) (MACROCYCLICS, DOTA-NHS ester, Plano, Texas, USA) and methionine(marker) were conjugated. The DOTA-HNS ester-Methionine was labeled with Technetium-99m (Inter-Medical, Technetium-99m, Bergamo, Italy). The synthesized radiopharmaceutical was used in SPECT/CT imaging for breast cancer diagnosis. For radiopharmaceutical evaluation, MTT assay for cellular toxicity, biodistribution, cellular uptake and radiochemical purity were employed.Technetium-99m-(DOTA-NHS-ester)-Methionine radiochemical had less cellular toxicity in human embryonic kidney cells 293 cell line (HEK293). Cellular uptake was indicated higher percent with use of Methionine as a marker, and radiochemical purity was high.Based on the results Technetium-99m-(DOTA-NHS-ester)-Methionine radiochem may be a better option for early detection of breast cancer. Further study is recommended to confirm these findings in clinical practice.

Glutathione Supplementation of Parenteral Nutrition Prevents Oxidative Stress and Sustains Protein Synthesis in Guinea Pig Model.

Peroxides contaminating parenteral nutrition (PN) limit the use of methionine as a precursor of cysteine. Thus, PN causes a cysteine deficiency, characterized by low levels of glutathione, the main molecule used in peroxide detoxification, and limited growth in individuals receiving long-term PN compared to the average population. We hypothesize that glutathione supplementation in PN can be used as a pro-cysteine that improves glutathione levels and protein synthesis and reduces oxidative stress caused by PN. One-month-old guinea pigs (7–8 per group) were used to compare glutathione-enriched to a non-enriched PN, animals on enteral nutrition were used as a reference. PN: Dextrose, amino acids (Primene), lipid emulsion (Intralipid), multivitamins, electrolytes; five-day infusion. Glutathione (GSH, GSSG, redox potential) and the incorporation of radioactive leucine into the protein fraction (protein synthesis index) were measured in the blood, lungs, liver, and gastrocnemius muscle. Data were analysed by ANOVA; p < 0.05 was considered significant. The addition of glutathione to PN prevented the PN-induced oxidative stress in the lungs and muscles and supported protein synthesis in liver and muscles. The results potentially support the recommendation to add glutathione to the PN and demonstrate that glutathione could act as a biologically available cysteine precursor.

Antigen receptor control of methionine metabolism in T cells.

Immune activated T lymphocytes modulate the activity of key metabolic pathways to support the transcriptional reprograming and reshaping of cell proteomes that permits effector T cell differentiation. The present study uses high resolution mass spectrometry and metabolic labelling to explore how murine T cells control the methionine cycle to produce methyl donors for protein and nucleotide methylations. We show that antigen receptor engagement controls flux through the methionine cycle and RNA and histone methylations. We establish that the main rate limiting step for protein synthesis and the methionine cycle is control of methionine transporter expression. Only T cells that respond to antigen to upregulate and sustain methionine transport are supplied with methyl donors that permit the dynamic nucleotide methylations and epigenetic reprogramming that drives T cell differentiation. These data highlight how the regulation of methionine transport licenses use of methionine for multiple fundamental processes that drive T lymphocyte proliferation and differentiation.

Is the Hoffman Effect for Methionine Overuse Analogous to the Warburg Effect for Glucose Overuse in Cancer?

The general cancer-specific metabolic defect of methionine (MET) dependence is due to MET overuse for aberrant transmethylation reactions. The excess use of MET for aberrant transmethylation reactions apparently diverts methyl groups from DNA. The resulting global DNA hypomethylation is also a general phenomenon in cancer and leads to unstable genomes and aneuploid karyotypes. The excessive and aberrant use of MET in cancer is readily observed in [11C]-MET-PET imaging, where high uptake of [11C]-MET results in a very strong and selective tumor signal compared to normal tissue background for brain cancer and possibly other cancers. [11C]-MET is superior to [18C]-fluorodeoxyglucose (FDG) for PET imaging, suggesting that MET overuse in cancer ("Hoffman effect") is greater than glucose overuse in cancer ("Warburg effect").

A Fast Photochemical Oxidation of Proteins (FPOP) platform for free-radical reactions: the carbonate radical anion with peptides and proteins

Fast Photochemical Oxidation of Protein (FPOP), based on a pulsed KrF laser (248 nm) for free-radical generation, is a biophysical method that utilizes hydroxyl radicals to footprint proteins in solution. FPOP has been recognized for structural proteomics investigations, including epitope mapping, protein-aggregation characterization, protein-folding monitoring, and binding-affinity determination. The distinct merits of the platform are: i) the use of a scavenger to control radical lifetime and allow fast (“snapshot”) footprinting of solvent-accessible residues in a protein; ii) the employment of a flow system to enable single-shot irradiation of small plugs of the targeted sample; iii) the use of methionine and catalase after radical oxidation chemistry to prevent post-oxidation with residual oxidizing species; and iv) the utilization of mature mass spectrometry-based proteomic methods to afford detailed analysis. In addition to •OH, other reactive reagents (e.g., carbenes, iodide, sulfate radical anion, and trifluoromethyl radical) can be implemented on this platform to increase the versatility and scope. In this study, we further elaborate the use of FPOP platform to generate secondary radicals and establish a workflow to answer fundamental questions regarding the intrinsic selectivity and reactivity of radicals that are important in biology. Carbonate radical anion is the example we chose owing to its oxidative character and important putative pathogenic roles in inflammation. This systematic study with model proteins/peptides gives consistent results with a previous study that evaluated reactivity with free amino acids and shows that methionine and tryptophan are the most reactive residues with CO3-•. Other aromatic amino acids (i.e., tyrosine, histidine and phenylalanine) exhibit moderate reactivity, whereas, aliphatic amino acids are inert, unlike with •OH. The outcome demonstrates this approach to be appropriate for studying the fast reactions of radicals with proteins.

Expression of genes that encode cellular oxidant/antioxidant systems are affected by heat stress.

Heat stress causes critical molecular dysfunction that affects productivity in chickens. Thus, the purpose of this study was to evaluate the effect of heat stress (HS) on the expression of select genes in the oxidation/antioxidation machinery in the liver of chickens. Chickens at 14days of age were randomly assigned to two treatment groups and kept under either a constant normal temperature (25°C) or high temperature (35°C) in individual cages for 12 days. mRNA expression of Nrf2, oxidants NADPH(NOX): [NOX1, NOX2, NOX3, NOX4, NOX5 and DUOX2], and antioxidants [SOD1, CAT, GR, GPx1, NQO1] in the liver were analyzed at 1 and 12days post-HS. We show that, HS changes the mRNA expression of oxidants thereby increasing cellular reactive oxygen species (ROS). Additionally, persistent HS up-regulates SOD which converts superoxides to hydrogen peroxide. We further demonstrated the dynamic relationship between catalase, GSH peroxidase (GPx) and NADPH under both acute and chronic heat stress. The pentose phosphate pathway could be important under HS since it generates NADPH which serves as a cofactor for GPx. Also, methionine, a precursor of cysteine has been shown to have reducing properties and thereby makes for an alternative fuel for redox processes. Genes in the ROS and antioxidant generation pathways may provide insight into nutritional intervention strategies, especially the use of methionine and/or cysteine when birds are suffering from heat stress.

Abstract 2134: Use of methionine gamma-lyase-loaded erythrocytes to induce effective methionine depletion in cancer therapy

Abstract Methionine (Met) dependence is a cancer-specific metabolic defect that has emerged as a target during the last two decades. The use of methionine gamma-lyase (MGL; EC number 4.4.1.11), a bacterial Met-catabolizing enzyme, is a promising strategy for treatment of Met-dependent cancers. However, one challenge is that MGL has a very short half-life (~2 hours), resulting in a short-term Met depletion in vivo. Additionally, its cofactor, pyridoxal 5’-phosphate (PLP) is rapidly eliminated from plasma (Yang et al., 2004). PEGylation extends the MGL half-life in mice to up to 38 hours. Nevertheless, frequent injections are still necessary for maintaining an effective Met depletion over time (Sun et al., 2003). In addition, the low bioavailability of PLP remains a major hurdle due to both scavenging by plasma proteins and very short half-life (&amp;lt; 15 minutes) in the blood stream (Zempleni, 1995). Studies showed that pyridoxine (PN), a vitamin B6 vitamer, can easily cross red blood cells (RBCs) membrane to be rapidly converted to PLP via an enzymatic reactions cascade (Anderson et al., 1971). Considering those particular characteristics of RBCs, we propose that RBC-encapsulated MGL (ERY-MET) will protect the enzyme from degradation/immune reactions and therefore overcome the pharmacodynamic limitations for its use in the treatment of Met-dependent cancers. Pharmacokinetics, pharmacodynamics, and safety parameters of MGL-loaded RBCs were evaluated in healthy mice. In parallel, the role of RBC in PLP biosynthesis from exogenous uptake of PN was investigated in vivo. Finally, we investigated the antitumoral effect of repeated injections of MGL-loaded RBCs combined with daily intragastric administration of PN in two subcutaneous xenografted mouse models for human gastric and glioblastoma tumors. The MGL half-life increased from &amp;lt; 24 hours to ~ 10 days when encapsulated in RBC, with no toxicity reported after one injection of ERY-MET. Following intragastric administration (3.2 mg/kg), PN was rapidly (15 minutes) converted into PLP within the RBC, resulting in an increase of MGL activity (holoenzyme). Combining a weekly single intravenous injection of ERY-MET for 5 days, in association with daily PN supplementation by gavage led to a sustained Met depletion in plasma and induced a 85% inhibition of tumor growth 45 days following implantation of glioblastoma cells. In the gastric mouse model, tumor growth was inhibited by 72% at the same time point (45 days).This study clearly demonstrated that encapsulation of MGL in erythrocytes both strongly improved the half-life and contributed to provide active cofactor. In parallel, repeated injections of ERY-MET were effective against tumor growth in mouse models. Thus, due to the RBC intrinsic characteristics, ERY-MET represents a new promising treatment against a broad scope of cancers that rely on Met metabolism. Citation Format: Fabien Gay, Karine Aguera, Karine Senechal, Philip Lorenzi, Alexander Scheer, Françoise Horand, Vanessa Bourgeaux. Use of methionine gamma-lyase-loaded erythrocytes to induce effective methionine depletion in cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2134. doi:10.1158/1538-7445.AM2017-2134

Comparative investigation of methionine and novel formulation Metovitan protective effects in Wistar rats with testicular and epididymal toxicity induced by anti-tuberculosis drugs co-administration

Despite clear beneficial effects, studies on the efficacy of different formulations of micronutrients and vitamins in the treatment of male infertility are still very limited. The aim of the study was to compare the efficacy of methionine and novel formulation Metovitan based on the combination of methionine, thiamine, nicotinamide, α-tocopherol acetate and zinc salt as remedies for prevention of anti-tuberculosis drugs (ATD) anti-fertility effects in male rats. ATD co-administration resulted in testicular CYP2E1, CYP2C23 and CYP3A2 transcriptional activation. Methionine and Metovitan regulated the level of CYP2E1 and CYP3A2 mRNA expression. Methionine unaffected CYP2C23 mRNA level, while Metovitan effectively normalized this parameter. The use of methionine did not allow normalizing of DNA fragmentation processes in testes, while Metovitan provided decrease in the number of DNA fragments to the control level. Both substances significantly decreased p-nitrophenol hydroxylase activity and prevented pro/antioxidant parameters imbalance in testes of ATD-treated rats. The end results of methionine and Metovitan application were partial or complete restoration of altered spermatogenesis parameters with subsequent increase in sperm count and fertility. Ameliorating effects may be attributed to antioxidant properties and modulating effects on testicular CYPs. More pronounced beneficial Metovitan effects might be due to synergic effects of its components.

Alternative ingredients for providing adequate methionine in organic poultry diets in the United States with limited synthetic amino acid use

Synthetic methionine use is currently limited to 1 kg and 1.5 kg per metric tonne (2, 2, and 3 lbs per short ton) of feed for organic laying hens, broilers, and turkeys and other poultry, respectively, in the United States of America. All other synthetic amino acids (AA) have been banned from use in organic poultry diets in this country. It is challenging to provide sufficient methionine (Met) to maintain bird growth and productive performance up to current industry standards given the recent restrictions that have been placed on synthetic Met. Without synthetic AA, Met requirements can alternatively be obtained for organic poultry by dramatically increasing dietary crude protein (CP) e.g. via additional inclusion of expeller-pressed soybean meal to the diets. However, this strategy leads to both major increases in feed costs and environmental concerns due to increasing nitrogen excretion, with concurrent rises in ammonia emissions, and corresponding welfare issues due to ammonia and litter quality. This review aims to examine feed ingredients that may contribute to a solution to this issue. Otherwise, further negative impacts may soon be felt from the current limitation on synthetic Met or a potential ban on its entire use in the future.

Methionine Uptake and Required Radiation Dose to Control Glioblastoma

The purpose of this study was to retrospectively assess the feasibility of radiation therapy planning for glioblastoma multiforme (GBM) based on the use of methionine (MET) positron emission tomography (PET), and the correlation among MET uptake, radiation dose, and tumor control. Twenty-two patients with GBM who underwent MET-PET prior to radiation therapy were enrolled. MET uptake in 30 regions of interest (ROIs) from 22 GBMs, biologically effective doses (BEDs) for the ROIs and their ratios (MET uptake:BED) were compared in terms of whether the ROIs were controlled for >12 months. MET uptake was significantly correlated with tumor control (odds ratio [OR], 10.0; P = .005); however, there was a higher level of correlation between MET uptake:BED ratio and tumor control (OR, 40.0; P < .0001). These data indicated that the required BEDs for controlling the ROIs could be predicted in terms of MET uptake; BED could be calculated as [34.0 × MET uptake] Gy from the optimal threshold of the MET uptake:BED ratio for tumor control. Target delineation based on MET-PET was demonstrated to be feasible for radiation therapy treatment planning. MET-PET could not only provide precise visualization of infiltrating tumor cells but also predict the required radiation doses to control target regions.

Effect of methionine on hepatic indices in male Wistar rat dosed to acetaminophen formulation

Studies’ reports in both humans and experimental animals have supported the use of methionine as an effective antidote to counteract the manifestation of hepatotoxicity, which is a common occurrence of acetaminophen at overdose levels of exposure. This study was embarked on to test the hepatoprotective effect of methionine in acetaminophen tablets, produced by a leading paracetamol brand in Nigeria especially in ameliorating the hepatocellular damage for which acetaminophen is noted for. Ten percent methionine was detected in this formulation using HPLC technique. Twenty male Wistar rats were used for this purpose, they were divided equally into four groups, and the first group served as the control and received 2 ml of physiologic saline per rat. The other three groups served as the test groups and received 100, 350 and 1000 mg\kg BW of acetaminophen dissolved in 2 ml of physiologic saline per rat. The drug was introduced into the rats by intra-peritoneal route of administration. The study lasted for 48 h after which the animals were sacrificed and blood obtained by cardiac puncture. Results showed that all these hepatotoxic indices and liver function tests (aspartate and alanine amino transferases, alkaline phoshatase, total and conjugated bilirubin, total proteins, albumin and globulins) of rats in both 350 and 1000 mg\kg levels were not statistically different compared to the controls (p > 0.05). The rats in the 100 mg\kg set showed the same pattern except that total proteins and globulins were statistically increased in these rats compared to controls (p < 0.05). These results therefore, show that methionine containing acetaminophen in tablet form ameliorated the toxic effects of acetaminophen even at toxic level of 1000 mg\kg level BW. Key words: Hepatocellular damage, male Wistar rats, acetaminophen formulation.

Effects ofdl-2-hydroxy-4-methylthiobutyrate on the first-pass intestinal metabolism of dietary methionine and its extra-intestinal availability

The present study was conducted in a one-factorial arrangement to determine the effects of dl-2-hydroxy-4-methylthiobutyrate (dl-HMTB) on the first-pass intestinal metabolism of dietary methionine and its extra-intestinal availability. Barrows (n 6; aged 35 d; weight 8.6 kg), implanted with arterial, portal, mesenteric and gastric catheters, were fed a diet containing dl-methionine (dl-MET) or dl-HMTB once hourly and infused intramesenterically with 1 % p-aminohippurate and intragastrically with [1-13C]methionine at 7.0 mumol/kg body weight per h. Arterial and portal blood samples were taken at hourly intervals until 6 h of tracer infusion and pigs was then killed for collection of muscle, intestine, liver and kidney samples. The net portal appearance of methionine, expressed as the fraction of ingested directly available l-methionine, was higher (P < 0.05) in the dl-HMTB than in the dl-MET diet, and there was no difference (P = 0.26) in the fractional portal balance of [1-13C]methionine between the diets. [1-13C]methionine enrichment (tracer:tracee ratio; mol/100 mol amino acid) in the jejunum, arterial and portal plasma, liver, kidney and muscle was also not different (P>0.05) between the groups. Over the 6 h period after the start of feeding, the average concentration of citrulline both in the arterial and portal plasma was higher (P < 0.05) in the dl-HMTB than in the dl-MET group, and arterial plasma ornithine and taurine concentration was also higher (P < 0.05) in the dl-HMTB than in the dl-MET group. However, plasma urea concentration both in the arterial and portal vein was lower (P < 0.05) in the dl-HMTB than in the dl-MET group. These results suggested that the potential difference in the first-pass use of methionine by the intestine between the dl-HMTB and dl-MET diets might affect intestinal and systemic metabolism of other amino acids, which may provide new important insights into nutritional efficiency of different methionine sources.