Comparative Study Of Metabolism Research Articles

Preparation and pharmacokinetic evaluation of a sertraline-methylpropyphenazone prodrug: a comparative metabolic study on the plasma and brain tissues of rats using LC-MS/MS analysis.

A mutual prodrug of sertraline-methylpropyphenazone (SER-MP) was prepared and characterized using a spectral method. The yield of the prepared SER-MP was 90%, and its purity reached 98.8%. The metabolic fate of the prepared SER-MP versus sertraline (SER) was investigated in the plasma and brain tissues of rats. A solid-phase extraction procedure was developed and validated for the optimal recovery of SER, 3-hydroxymethylpropyphenazone (3-OHMP), and SER-MP from plasma and brain tissues. The extraction efficiency for the targeted analytes was improved from 93.5% to 98.0% using Chromabond® C8-100 mg solid-phase extraction columns. A high-performance liquid chromatography-triple-quad-mass spectrometric method was developed and validated to quantify the SER, SER-MP, and potential metabolites. The pharmacokinetic parameters showed that the time to reach the maximum plasma concentration (t max) for both SER and SER-MP was 6 hours, and the maximum plasma concentration of SER-MP reached 192 ng mL-1 with an elimination half-life time of 50 hours. The plasma level of SER, which was released as a metabolite of orally administered SER-MP, was increased by 2.4 times compared to SER HCl administered at equimolar doses. The concentration of SER-MP in the rat brains remained approximately stable at 100 ng g-1 for 0.5 to 192 hours. The serotonin level in the rat brain homogenate was 50 to 90 ng g-1 for both the group receiving SER and that receiving an equal molar dose of SER-MP. This observation was consistent during a time range of 1 to 192 h from oral administration. Thus, this approach could lead to the development of more efficient antidepressant therapies with reduced side effects. The findings indicate that SER-MP could minimize serotonin syndrome risks by maintaining steady serotonin levels in the brain, thus improving patient safety and compliance.

Comparative metabolic study of planktonic and sessile cells in Salmonella Enteritidis ATCC 13076: Elucidating metabolic pathways driving biofilm formation.

Microorganisms tend to accumulate on surfaces, forming aggregates such as biofilms, which grant them resistance to various environmental stressors and antimicrobial agents. This ability has hindered the effective treatment of diseases caused by pathogenic microorganisms, including Salmonella, which is responsible for a significant number of deaths worldwide. This study aimed to compare the metabolic profiles of planktonic and sessile cells of Salmonella Enteritidis using a metabolomics approach. The metabolites extracted from the bacterial cells were analyzed by LC/MS approach. Raw data were analyzed using Thermo Xcalibur v 3.1 software. For data processing, XCMS was used for feature detection, retention time, correction and alignment. The data matrix was analyzed by uni- and multivariate statistical methods (PCA, PLS-DA, Heatmap) in MetaboAnalyst software v 6.0. A total of 121 metabolites were presumptively identified as differential metabolic characteristics between the two bacterial states, and they were associated with their corresponding metabolic pathways. Among the metabolites that exhibited positive modulation in planktonic cells were proline, phenylalanine, which act as precursors of essential metabolites and part of the stress adaptation mechanisms. In addition, putrescine and cadaverine, play crucial roles in growth, stress response, and cell stability In contrast, the most representative metabolites in sessile cells included lysine, adenosine, purines, pyrimidines, and citrate, mainly associated with maintaining cellular homeostasis, stress response and metabolic regulation. Finally, pathway enrichment analysis identified metabolic changes in 11 pathways, predominantly involving purine and pyrimidine metabolism, arginine and proline metabolism, and vitamin B6 metabolism. These findings facilitated the identification of potential metabolic pathways associated with biofilm formation in the sessile cells of Salmonella Enteritidis.

A comparative study of bioenergetic metabolism on mammary epithelial cells from humans and Göttingen Minipigs

Mammary epithelial cells (MECs) of humans (h) and Göttingen Minipigs (mp) were analyzed to compare their ability to perform ATP production by oxidative phosphorylation and glycolysis. The ATP production under basal and stressor situations highlights the same metabolic potential of both primary cell lines. However, quantitively the ATP production rate of hMECs was higher than mpMECs. Conversely, oxidative cell respiration in mpMECs exploits a maximum respiratory capacity to support pathophysiological circumstances or stress conditions that could require an excessive effort of cell metabolism. Since mpMECs primarily utilize an oxidative metabolism similar to hMECs, the metabolic characterization conducted allows us to confirm that mpMECs represent a potential alternative cellular model in the translational medicine approach.

High intraspecific variability and previous experience affect polyphenol metabolism in polyphagous Lymantria mathura caterpillars.

Polyphagous insect herbivores feed on multiple host-plant species and face a highly variable chemical landscape. Comparative studies of polyphagous herbivore metabolism across a range of plants is an ideal approach for exploring how intra- and interspecific chemical variation shapes species interactions. We used polyphagous caterpillars of Lymantria mathura (Erebidae, Lepidoptera) to explore mechanisms that may contribute to its ability to feed on various hosts. We focused on intraspecific variation in polyphenol metabolism, the fates of individual polyphenols, and the role of previous feeding experience on polyphenol metabolism and leaf consumption. We collected the caterpillars from Acer amoenum (Sapindaceae), Carpinus cordata (Betulaceae), and Quercus crispula (Fagaceae). We first fed the larvae with the leaves of their original host and characterized the polyphenol profiles in leaves and frass. We then transferred a subset of larvae to a different host species and quantified how host shifting affected their leaf consumption and polyphenol metabolism. There was high intraspecific variation in frass composition, even among caterpillars fed with one host. While polyphenols had various fates when ingested by the caterpillars, most of them were passively excreted. When we transferred the caterpillars to a new host, their previous experience influenced how they metabolized polyphenols. The one-host larvae metabolized a larger quantity of ingested polyphenols than two-host caterpillars. Some of these metabolites could have been sequestered, others were probably activated in the gut. One-host caterpillars retained more of the ingested leaf biomass than transferred caterpillars. The pronounced intraspecific variation in polyphenol metabolism, an ability to excrete ingested metabolites and potential dietary habituation are factors that may contribute to the ability of L. mathura to feed across multiple hosts. Further comparative studies can help identify if these mechanisms are related to differential host-choice and response to host-plant traits in specialist and generalist insect herbivores.

Comparative metabolic study of the chloroform fraction of three Cystoseira species based on UPLC/ESI/MS analysis and biological activities

This study aims to investigate the phytoconstituents of the chloroform fraction of three Cystoseira spp. namely C. myrica, C. trinodis, and C. tamariscifolia using UPLC/ESI/MS technique. The results revealed the identification of 19, 20 and 11 metabolites in C. myrica, C. trinodis, and C. tamariscifolia, respectively mainly terpenoids, flavonoids, phenolic acids and fatty acids. Also, an in vitro antioxidant study using FRAP and DPPH assays was conducted where the chloroform fraction of C. trinodis displayed the highest antioxidant activity in both assays, which would be attributed to its highest total phenolics and total flavonoids. Besides, the investigation of COX-1, α-glucosidase and α-amylase inhibitory activities were performed. Regarding C. trinodis, it showed the strongest inhibitory activity towards COX-1. Moreover, it showed potent inhibitory activity towards α-glucosidase and α-amylase enzymes. According to the molecular docking studies, the major compounds characterised showed efficient binding to the active sites of the target enzymes.

A Comparative Study of Calcium Metabolism between Quail and Domestic Rabbits

The existing study was conducted to evaluate calcium; vitamin D and calcitonin concentration in two types of amniotes that live in the Iraqi environment include the local rabbit and the Japanese quail. The study included 18 female Japanese quail Coturnix coturnix, weighing 145.5 ± 34.341 g, they were 16 weeks in ages and 18 female local rabbits, Oryctolagus cuniculus, at the age of one years and 1438.5 ± 284.988 g in weight. The results showed that the mean serum calcium concentration in bird and rabbit were 8.134±0.450 (mg/dl) and 7.267±1.761 (mg/dl) respectively and it was significantly at at 0.066 higher in bird in comparison to rabbit, the mean of vitamin D in bird and rabbit were 24.22± 3.159 (ng/ml) and 28.43±4.632 (ng/ml) respectively and it was significantly higher in rabbit than bird at 0.007 while the mean serum calcitonin concentration in bird and rabbit were 1.354±0.1960 (mg/dl) and 1.676±0.4151 (mg/dl) respectively and it was significantly at 0.009 higher in rabbit in comparison to bird. Egg laying, shell calcification and medullary bone formation induce more extra demand of calcium in birds while the high rate of teeth erupting demand extra calcium in rabbits, the metabolism of vitamin D will be altered indirectly by these process which associated with increased requirements for calcium. The study showed an increase in the level of calcium in both rabbits and quail birds, and that this increase will change the metabolism of vitamin D, and many physiological processes will occur.

A comparative study of posterior cingulate metabolism in patients with mild cognitive impairment due to Parkinson's disease or Alzheimer's disease

Few comparative studies have assessed metabolic brain changes in cognitive impairment among neurodegenerative disorders, and the posterior cingulate cortex (PCC) is a metabolically active brain region with high involvement in multiple cognitive processes. Therefore, in this study, metabolic abnormalities of the PCC were compared in patients with mild cognitive impairment (MCI) due to Parkinson’s disease (PD) or Alzheimer’s disease (AD), as examined by proton magnetic resonance spectroscopy (1H-MRS). Thirty-eight patients with idiopathic PD, including 20 with mild cognitive impairment (PDMCI) and 18 with normal cognitive function (PDN), 18 patients with probable mild cognitive impairment (ADMCI), and 25 healthy elderly controls (HCs) were recruited and underwent PCC 1H-MRS scans. Compared with HCs, patients with PDMCI exhibited significantly reduced concentrations of N-acetyl aspartate (NAA), total NAA (tNAA), choline (Cho), glutathione (GSH), glutamate + glutamine (Glx) and total creatine (tCr), while ADMCI cases exhibited significantly elevated levels of myo-inositol (Ins) and Ins/tCr ratio, as well as reduced NAA/Ins ratio. No significant metabolic changes were detected in PDN subjects. Compared with ADMCI, reduced NAA, Ins and tCr concentrations were detected in PDMCI. Besides, ROC curve analysis revealed that tCr concentration could differentiate PDMCI from PDN with an AUC of 0.71, and NAA/Ins ratio could differentiate patients with MCI from controls with normal cognitive function with an AUC of 0.74. Patients with PDMCI and ADMCI exhibited distinct PCC metabolic 1H-MRS profiles. The findings suggested cognitively normal PD patients with low NAA and tCr in the PCC might be at risk of preclinical PDMCI, and Ins and/or NAA/MI ratio in the PCC should be reconsidered a possible biomarker of preclinical MCI in clinical practice. So, comparing PCC’s 1H-MRS profiles of cognitive impairment among neurodegenerative illnesses may provide useful information for better defining the disease process and elucidate possible treatment mechanisms.

Comparative Metabolic Study of Tamarindus indica L.’s Various Organs Based on GC/MS Analysis, In Silico and In Vitro Anti-Inflammatory and Wound Healing Activities

The chemical composition of the n-hexane extract of Tamarindus indica's various organs-bark, leaves, seeds, and fruits (TIB, TIL, TIS, TIF)-was investigated using gas chromatography-mass spectrometry (GC/MS) analysis. A total of 113 metabolites were identified, accounting for 93.07, 83.17, 84.05, and 85.08 % of the total identified components in TIB, TIL, TIS, and TIF, respectively. Lupeol was the most predominant component in TIB and TIL, accounting for 23.61 and 22.78%, respectively. However, n-Docosanoic acid (10.49%) and methyl tricosanoate (7.09%) were present in a high percentage in TIS. However, α-terpinyl acetate (7.36%) and α-muurolene (7.52%) were the major components of TIF n-hexane extract. By applying a principal component analysis (PCA) and hierarchal cluster analysis (HCA) to GC/MS-based metabolites, a clear differentiation of Tamarindus indica organs was achieved. The anti-inflammatory activity was evaluated in vitro on lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. In addition, the wound healing potential for the n-hexane extract of various plant organs was assessed using the in-vitro wound scratch assay using Human Skin Fibroblast cells. The tested extracts showed considerable anti-inflammatory and wound-healing activities. At a concentration of 10 µg/mL, TIL showed the highest nitric oxide (NO) inhibition by 53.97 ± 5.89%. Regarding the wound healing potential, after 24 h, TIB, TIL, TIS, and TIF n-hexane extracts at 10 g/mL reduced the wound width to 1.09 ± 0.04, 1.12 ± 0.18, 1.09 ± 0.28, and 1.41 ± 0.35 mm, respectively, as compared to the control cells (1.37 ± 0.15 mm). These findings showed that the n-hexane extract of T. indica enhanced wound healing by promoting fibroblast migration. Additionally, a docking study was conducted to assess the major identified phytoconstituents' affinity for binding to glycogen synthase kinase 3-β (GSK3-β), matrix metalloproteinases-8 (MMP-8), and nitric oxide synthase (iNOS). Lupeol showed the most favourable binding affinity to GSK3-β and iNOS, equal to -12.5 and -13.7 Kcal/mol, respectively, while methyl tricosanoate showed the highest binding affinity with MMP-8 equal to -13.1 Kcal/mol. Accordingly, the n-hexane extract of T. indica's various organs can be considered a good candidate for the management of wound healing and inflammatory conditions.

Feasibility of establishing a veterinary marker to total residue in edible tissues with non-radiolabeled study using high-resolution mass spectrometry

Traditionally, in vivo metabolism and total residue studies in veterinary drug research were conducted using radiolabeled drug where information on metabolite profiles and marker residue to total residue ratio is obtained. The Veterinary International Conference on Harmonisation (VICH) guideline GL46 indicates that the metabolism and residue kinetics in food-producing animals may be documented by an alternative approach, one other than the traditional radiolabeled study. High-resolution mass spectrometry (HRMS) has been widely used in human pharmaceutical R&D from metabolite profiling and identification in early drug discovery to first-in-human (FIH) studies in development. Recent advances in data mining tools have greatly improved the metabolite profiling capability with HRMS. It is now routine to study metabolism using non-radiolabeled samples without missing any major metabolites. In the current paper, we explored the feasibility of conducting non-radiolabeled marker residue studies to obtain metabolism information using HRMS. Metabolite profiles of gamithromycin in edible tissues of sheep treated with 6 mg/kg body weight subcutaneous injections were obtained with HRMS. The semi-quantitative relationship between the level of gamithromycin and the total treatment-related residues was established by determining the percentages of extracted ion chromatograms for metabolites and parent compound residues in each tissue. Major components (gamithromycin and its metabolite, declad) were measured quantitatively using a validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Metabolite profiles in excreta were also obtained and the major components measured quantitatively with a LC-MS/MS method to ensure no major metabolite was missing. Combining previous knowledge of marker residue studies in cattle and swine, as well as an in vitro comparative metabolism study with metabolite data across various species, gamithromycin was designated as the marker residue in sheep edible tissues. The marker to total residue ratios were established using a combination of the semi-quantitative HRMS results and quantitative results with the major components: the marker residue and declad. The pros and cons of the HRMS method as well as the appropriate use of the method for marker residue studies are discussed.

Comparative Metabolic Study of Two Contrasting Chinese Cabbage Genotypes under Mild and Severe Drought Stress

Chinese cabbage (Brassica rapa L. ssp. pekinensis) is an important leafy vegetable crop cultivated worldwide. Drought is one of the most important limiting factors for the growth, production and quality of Chinese cabbage due to its weak drought tolerance. In order to deepen the understanding of drought stress response in Chinese cabbage, metabolomics studies were conducted in drought−tolerant (DT) and drought−susceptible (DS) genotypes of Chinese cabbage under water deficit−simulated mild and severe drought stress conditions. A total of 777 metabolites were detected, wherein 90 of them were proposed as the drought−responsive metabolites in Chinese cabbage, with abscisic acid (ABA), serine, choline alfoscerate, and sphingosine as potential representative drought stress biomarkers. We also found that drought−tolerant and drought−susceptible genotypes showed differential metabolic accumulation patterns with contrasting drought response mechanisms. Notably, constitutively high levels of ABA and glutathione were detected in drought−tolerant genotype in all tested and control conditions. In addition, proline, sucrose, γ−aminobutyric acid, and glutathione were also found to be highly correlated to drought tolerance. This study is the first metabolomic study on how Chinese cabbage responds to drought stress, and could provide insights on how to develop and cultivate new drought−resistant varieties.

CE with Cu2+ ions and 2-hydroxypropyl-β-cyclodextrin additives for the investigation of amino acids composition of the culture medium in a cellular model of non-alcoholic fatty liver disease

CE method with CuSO4 and 2-hydroxypropyl-β-cyclodextrin additives in sodium acetate background electrolyte pH 4.3 for the simultaneous determination of amino acids and lactic acid was adapted for the comparative study of metabolism in "healthy" and non-alcoholic fatty liver disease model cells HepG2. In vitro model of the disease was developed by exposure HepG2 cells with oleate and palmitate to simulate an excessive flow of fatty acids into hepatocytes. The model was proven to be consistent with the disease pathophysiology, since intracellular triglyceride and cytokine interleukin 8 levels were increased, while cells viability was decreased. In order to check whether the metabolism of amino acids changes in pathology, we proposed sample preparation of culture medium and characterized the CE method by evaluating linear dynamic range, repeatability and intermediate precision of peak areas and migration times, accuracy (recovery rate and trueness estimated by reference method), detection limits and quantitation limits. The method proved to be sensitive, reliable and highly accurate for the quantitation of amino acids and lactic acid. The concentrations of amino acids in the culture medium of healthy and the disease model cells were measured and altered levels of Arg, Ala, Glu, Gln and lactic acid have been found in comparison to health control.

Knockout of Arabidopsis thaliana VEP1, Encoding a PRISE (Progesterone 5β-Reductase/Iridoid Synthase-Like Enzyme), Leads to Metabolic Changes in Response to Exogenous Methyl Vinyl Ketone (MVK).

Small or specialized natural products (SNAPs) produced by plants vary greatly in structure and function, leading to selective advantages during evolution. With a limited number of genes available, a high promiscuity of the enzymes involved allows the generation of a broad range of SNAPs in complex metabolic networks. Comparative metabolic studies may help to understand why—or why not—certain SNAPs are produced in plants. Here, we used the wound-induced, vein patterning regulating VEP1 (AtStR1, At4g24220) and its paralogue gene on locus At5g58750 (AtStR2) from Arabidopsis to study this issue. The enzymes encoded by VEP1-like genes were clustered under the term PRISEs (progesterone 5β-reductase/iridoid synthase-like enzymes) as it was previously demonstrated that they are involved in cardenolide and/or iridoid biosynthesis in other plants. In order to further understand the general role of PRISEs and to detect additional more “accidental” roles we herein characterized A. thaliana steroid reductase 1 (AtStR1) and compared it to A. thaliana steroid reductase 2 (AtStR2). We used A. thaliana Col-0 wildtype plants as well as VEP1 knockout mutants and VEP1 knockout mutants overexpressing either AtStR1 or AtStR2 to investigate the effects on vein patterning and on the stress response after treatment with methyl vinyl ketone (MVK). Our results added evidence to the assumption that AtStR1 and AtStR2, as well as PRISEs in general, play specific roles in stress and defense situations and may be responsible for sudden metabolic shifts.

Mechanism of action and selectivity of a novel herbicide, fenquinotrione.

Fenquinotrione is a novel herbicide that can control a wide range of broadleaf and sedge weeds with excellent rice selectivity. We revealed that fenquinotrione potently inhibited the 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity in Arabidopsis thaliana with an IC50 of 44.7 nM. The docking study suggested that the 1,3-diketone moiety of fenquinotrione formed a bidentate interaction with Fe(II) at the active site. Furthermore, π–π stacking interactions occurred between the oxoquinoxaline ring and the conserved Phe409 and Phe452 rings, indicating that fenquinotrione competes with the substrate, similar to existing HPPD inhibitors. A more than 16-fold difference in the herbicidal activity of fenquinotrione in rice and the sedge, Schoenoplectus juncoides, was observed. However, fenquinotrione showed high inhibitory activity against rice HPPD. Comparative metabolism study suggested that the potent demethylating metabolism followed by glucose conjugation in rice was responsible for the selectivity of fenquinotrione.

Comparative metabolism study on chlorogenic acid, cryptochlorogenic acid and neochlorogenic acid using UHPLC-Q-TOF MS coupled with network pharmacology.

Chlorogenic acid (5-CQA), neochlorogenic acid (3-CQA), and cryptochlorogenic acid (4-CQA), usually simultaneously exist in many traditional Chinese medicines (TCMs). However, insufficient attentions have been paid to the comparative metabolism study on these three isomeric constituents with similar effects on anti-inflammation until now. In this study, a novel strategy was established to perform comparative analysis of their metabolic fates in rats and elucidate the pharmacological mechanism of anti-inflammation. Firstly, diagnostic product ions (DPIs) deduced from the representative reference standards were adopted to rapidly screen and characterize the metabolites in rat plasma, urine and faeces using UHPLC-Q-TOF MS. Subsequently, Network pharmacology was utilized to elucidate their anti-inflammatory mechanism. Consequently, a total of 73 metabolites were detected and characterized, including 50, 47 and 43 metabolites for 5-CQA, 4-CQA and 3-CQA, orderly. Moreover, the network pharmacology study indicated that these three isomeric constituents and their major metabolites with similar in vivo metabolic pathways exerted anti-inflammatory effects through co-owned 20 biological processes, which involved 10 major signal pathways and 159 potential targets. Our study shed light on the similarities and differences of the metabolic profiling and anti-inflammatory activity among these three isomeric constituents and set an example for the further researches on the active mechanism of isomeric constituents existing in TCMs based on comparative metabolism study.

Comparative metabolic study of Citrus sinensis leaves cultivars based on GC–MS and their cytotoxic activity

Citrus sinensis L. Osbeck, (family Rutaceae), known as sweet orange, is a fruit-bearing shrub that widely cultivated all over the world due to its nutritive value, nutraceutical attributes and economic importance. In the present study, a comparative metabolic profile study of the essential oils of the leaves of nine cultivars of Citrus sinensis cultivated in Egypt was carried out based on GC–MS analysis coupled to chemometrics. A total of 47 compounds were identified, where monoterpenes hydrocarbons (61.39 %–78.26 %) represented the main recognized class in the essential oils. Sabinene (8.25 %–28.81 %), 2-carene (11.25 %–16.72 %) and cis-β-ocimene (10.22 %–13.93 %) were the major components identified in different cultivars. Chemometric analyses comprising Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) were experienced for their ability to discriminate between closely related cultivars. Both PCA score plot and HCA dendrogram could successfully segregate different cultivars based on their metabolic profiles. The MTT assay was used to evaluate the cytotoxicity of essential oils of Citrus sinensis leaves cultivars on different cell lines; MCF-7, HepG-2, HeLa, were all essential oils showed moderate cytotoxic activity. The MCF-7 cell lines were the most resistant cells with IC50 range from 243 to 343 μg/mL, while HeLa cells were the most sensitive cell lines IC50 range from 203 to 283 μg/mL. This may be attributed to the synergistic effects of different chemical components.

A comparative study of aurantio-obtusin metabolism in normal and liver-injured rats by ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry

Aurantio-obtusin, an anthraquinone isolated from cassiae semen, possesses diverse pharmacological activities, including hypotensive, hypolipidemic and anti-inflammatory effects. However, our previous studies demonstrated that exposure to aurantio-obtusin induced hepatotoxicity, but the mechanisms of the toxic effects remain unknown. The purpose of the present study is to establish a strategy for the metabolite profiling of aurantio-obtusin in normal and liver-injured rats. This study aimed at identifying the in vivo metabolites and the metabolic profiling in rats after oral administration at a dose of aurantio-obtusin (4 and 200 mg/kg) by using an ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and metabolynx™ software. A total of 39 metabolites were detected and 3 of them were compared with standard substances. The results indicated that the principal metabolism pathways of aurantio-obtusin in normal rats were glucuronidation and sulfation, while in rats with liver injury, demethylation, dehydroxylation and reduction were also observed and regarded as new metabolic patterns of aurantio-obtusin. These findings helped us to understand the pharmacological and toxicological mechanisms of aurantio-obtusin. Moreover, this study could help to elucidate the metabolic profiling of other anthraquinones.

Transcriptomic profiling of atrazine phytotoxicity and comparative study of atrazine uptake, movement, and metabolism in Potamogeton crispus and Myriophyllum spicatum

The accumulation of atrazine in sediments raises wide concern due to its potential negative effects on aquatic environments. Here we collected sediments and different submerged macrophytes to simulate natural shallow lakes and to measure atrazine levels and submerged macrophyte biomass. We determined gene expressions in submerged macrophytes treated with or without atrazine. We also examined atrazine concentrations and its metabolite structures in submerged macrophytes. When the initial concentration of atrazine in sediments ranged from 0.1 to 2.0 mg kg−1 dry weight (DW), atrazine levels in the pore water of the sediments ranged from 0.003 to 0.05 mg L−1 in 90 days. Atrazine did not show obvious long-term effects on the biomass of Potamogeton crispus and Myriophyllum spicatum (P > 0.05). On day 90, gene expressions related to cell wall in P. crispus were changed by atrazine phytotoxicity. Moreover, the decrease in the number genes controlling light-harvesting chlorophyll a/b-binding proteins verified the toxic effects of atrazine on the photosynthesis of M. spicatum. Compared with unexposed plants on day 90, ribosome pathway was significantly enriched with differentially expressed genes after submerged macrophytes were exposed to 2.0 mg kg−1 DW atrazine (P < 0.05). In addition, shoots and roots of P. crispus and M. spicatum could absorb the equal amount of atrazine (P > 0.05). Once absorbed by submerged macrophytes, atrazine was degraded into 1-hydroxyisopropylatrazine, hydroxyatrazine, deethylatrazine, didealkylatrazine, cyanuric acid, and biuret, and some of its metabolites could conjugate with organic acids, cysteinyl β-alanine, and glucose. This study establishes a foundation for aquatic ecological risk assessments and the phytoremediation of atrazine in sediments.

Assessment of cellular immunity in oil production operators with an imbalance of lipid metabolism

Introduction. Studies indicate the high pathogenetic significance of the immune component in the development of atherosclerosis. The aim of the study is a comparative assessment of immunological parameters in workers of petrochemical production with varying degrees of imbalance in lipid metabolism and the development of the atherosclerotic process. Materials and methods. Men working at an oil production enterprise in the Perm Region were examined. The observation group consisted of oil production operators with a diagnosis of atherosclerosis, the comparison group - with dyslipidemia syndrome. To determine the parameters of lipid metabolism, the results of a biochemical blood test were used. CD-immunogram parameters were identified by flow cytometry. Specific antibodies to benzene were determined by the allergosorbent method. Results. The results of a comparative study of fat metabolism confirmed violations of the physiological ratio of lipids in the blood of oil production workers, which were expressed in a significant imbalance in the levels of lipidogram. There was an increased level of specific IgG antibodies to benzene in the observation group in relation to the comparison group. An imbalance of cellular immunity was found, which was characterized by signs of indicators activation of cellular differentiation clusters. Conclusions. Studies of immune system compartments demonstrate excessive activation of cellular and humoral immunity in oil production workers under the influence of a combination of harmful production factors. The simultaneously formed imbalance of lipid metabolism is associated with various degrees of clinical manifestation of atherosclerotic disorders, with the influence of harmful production factors, aggressiveness of cellular and humoral immunity, and smoking.

Nontargeted lipidomics in nesting females of three sea turtle species in Florida by ultra-high-pressure liquid chromatography–high-resolution tandem mass spectrometry (UHPLC–HRMS/MS) reveals distinct species-specific lipid signatures

In recent years, the utility of lipidomics has been recognized in environmental toxicology and biomonitoring efforts due to the ubiquitous nature and importance of lipids in many cellular processes including signal transduction, energy storage, and cellular compartmentalization. Additionally, technological advances in high-resolution mass spectrometry have enabled the rapid expansion of the field, creating a surge in interest in comparative studies of lipid metabolism from a Systems Biology standpoint. Here, we adapted a nontargeted lipidomic approach for the study of plasma samples from nesting female leatherback (Dermochelys coriacea), loggerhead (Caretta caretta), and green (Chelonia mydas) sea turtles in Florida using ultra-high-performance liquid chromatography/high-resolution tandem mass spectrometry. We identified 877 lipids in common between the three species, of which the concentrations for 467 lipids were statistically different between two or more group comparisons. Principal component analysis revealed unique lipidomic signatures associated with each species of turtle, including various glycerophosphatidylcholines, glycerophosphatidylethanolamines, triacylglycerols, and oxidized triacylglycerols that were higher in leatherback sea turtles, diacylglycerols and select glycerophosphatidylinositols which were higher in loggerhead sea turtles, and specific plasmanyl-phosphatidylcholines that were higher in green sea turtles. Our results indicate that lipidomic profiling can be a useful tool for studying lipid metabolism and physiology of different species of sea turtles, while establishing baseline data that may be used as reference in future studies for observation of differences in life stages, for following spatial and temporal trends in nesting turtles, and for investigating population dynamics in response to various stressors.

Inhibitory and inductive effects of 4- or 5-methyl-2-mercaptobenzimidazole, thyrotoxic and hepatotoxic rubber antioxidants, on several forms of cytochrome P450 in primary cultured rat and human hepatocytes

Effects of 4-methyl-2-mercaptobenzimidazole (4-MeMBI) and 5-methyl-2- mercaptobenzimidazole (5-MeMBI) on cytochrome P450 (CYP) activity were examined in primary cultured rat hepatocytes. Hepatocytes from male Wistar rats were cultured in the presence of 4-MeMBI or 5-MeMBI (0−400 μM), and the activity of CYPs 3A2/4 (48 and 96 h) and 1A1/2 (48 h) was determined by measuring the activity of testosterone 6β-hydroxylation and 7-ethoxyresorufin O-deethylation, respectively. As a result, 4-MeMBI and 5-MeMBI (≥12.5 μM) inhibited CYP3A2 activity. On the other hand, 4-MeMBI (≥25 μM) and 5-MeMBI (≥100 μM) induced CYP1A1/2 activity, being consistent with the previous in vivo results. In a comparative metabolism study using primary cultured human hepatocytes from two Caucasian donors, 4-MeMBI and 5-MeMBI induced the activity of CYPs 3A4 and 1A1/2 with individual variability. It was concluded from these results that 4-MeMBI, 5-MeMBI and MBI caused inhibition of CYP3A2 activity in primary cultured rat hepatocytes, suggesting their potential for metabolic drug-drug interactions. Primary cultured rat and human hepatocytes were considered to be useful for the evaluation of effects of the benzimidazole compounds on their inducibility and inhibitory activities of cytochrome P450 forms.