A tau class glutathione S-transferase in tea plant, CsGSTU45, facilitates tea plant susceptibility to Colletotrichum camelliae infection mediated by jasmonate signaling pathway.

Tea plant [Camellia sinensis (L.) O. Kuntze], as one of the most important commercial crops, frequently suffers from anthracnose caused by Colletotrichum camelliae. The plant-specific tau (U) class of glutathione S-transferases (GSTU) participates in ROS homeostasis. Here, we identified a plant-specific GST tau class gene from tea plant, CsGSTU45, which is induced by various stresses, including C. camelliae infection, by analyzing multiple transcriptomes. CsGSTU45 plays a negative role in disease resistance against C. camelliae by accumulating H2 O2 . JA negatively regulates the resistance of tea plants against C. camelliae, which depends on CsGSTU45. CsMYC2.2, which is the key regulator in the JA signaling pathway, directly binds to and activates the promoter of CsGSTU45. Furthermore, silencing CsMYC2.2 increased disease resistance associated with reduced transcript and protein levels of CsGSTU45, and decreased contents of H2 O2 . Therefore, CsMYC2.2 suppresses disease resistance against C. camelliae by binding to the promoter of the CsGSTU45 gene and activating CsGSTU45. CsJAZ1 interacts with CsMYC2.2. Silencing CsJAZ1 attenuates disease resistance, upregulates the expression of CsMYC2.2 elevates the level of the CsGSTU45 protein, and promotes the accumulation of H2 O2 . As a result, CsJAZ1 interacts with CsMYC2.2 and acts as its repressor to suppress the level of CsGSTU45 protein, eventually enhancing disease resistance in tea plants. Taken together, the results show that the JA signaling pathway mediated by CsJAZ1-CsMYC2.2 modulates tea plant susceptibility to C. camelliae by regulating CsGSTU45 to accumulate H2 O2 .

Conserved Residues Lys64 and Glu78 at the Subunit Surface of Tau Glutathione Transferase in Rice Affect Structure and Enzymatic Properties.

Glutathione transferases (GSTs) are a superfamily of dimeric proteins associated with the detoxification of various reactive electrophiles and responsive to a multitude of stressors. We individually substituted Lys64 and Glu78 with Ala using site-directed mutagenesis to understand the role of subunit interactions in the structure and enzymatic properties of a rice GST (OsGSTU17). The wild-type OsGSTU17 lost the conserved hydrogen bond between subunits in tau class GSTs due to conserved Tyr92 replaced with Phe92, but still exhibited high substrate activities, and thermal stability remained in its dimeric structure. The significant decrease in thermal stability and obvious changes in the structure of mutant K64A implied that conserved Lys64 might play an essential role in the structural stability of tau class GSTs. The mutant E78A, supposed to be deprived of hydrogen and salt bonds between subunits, appeared in the soluble form of dimers, even though its tertiary structure altered and stability declined dramatically. These results suggest that the hydrogen and ionic bonds provided by conserved residues are not as important for OsGSTU17 dimerization and enzymatic properties. These results further supplement our understanding of the relationship between the structure and function of GSTs and provide a theoretical basis for improving crop resistance through targeted modification of GSTs.

Heterologous Expression and Catalytic Properties of Codon-Optimized Small-Sized Bromelain from MD2 Pineapple.

Bromelain is a unique enzyme-based bioactive complex containing a mixture of cysteine proteases specifically found in the stems and fruits of pineapple (Ananas comosus) with a wide range of applications. MD2 pineapple harbors a gene encoding a small bromelain cysteine protease with the size of about 19 kDa, which might possess unique properties compared to the other cysteine protease bromelain. This study aims to determine the expressibility and catalytic properties of small-sized (19 kDa) bromelain from MD2 pineapple (MD2-SBro). Accordingly, the gene encoding MD2-SBro was firstly optimized in its codon profile, synthesized, and inserted into the pGS-21a vector. The insolubly expressed MD2-SBro was then resolubilized and refolded using urea treatment, followed by purification by glutathione S-transferase (GST) affinity chromatography, yielding 14 mg of pure MD2-SBro from 1 L of culture. The specific activity and catalytic efficiency (kcat/Km) of MD2-SBro were 3.56 ± 0.08 U mg-1 and 4.75 ± 0.23 × 10-3 µM-1 s-1, respectively, where optimally active at 50 °C and pH 8.0, and modulated by divalent ions. The MD2-SBro also exhibited the ability to scavenge the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) with an IC50 of 0.022 mg mL-1. Altogether, this study provides the production feasibility of active and functional MD2-Bro as a bioactive compound.

Computational insights into diverse aspects of glutathione S-transferase gene family in Papaver somniferum.

Plant glutathione S-transferases are an ancient protein superfamily having antioxidant activity. These proteins are primarily involved in diverse plant functions such as plant growth and development, secondary metabolism, signaling pathways and defense against biotic and abiotic stresses. The current study aimed to comprehensively identify and characterize the GST gene family in the medicinally important crop Papaver somniferum. A total of 93 GST proteins were identified belonging to eight GST classes and found to be majorly localized in the cytoplasm. All GST genes were found on eleven opium chromosomes. Gene duplication analysis showed segmental duplication as a key factor for opium GST gene family expansion under strong purifying selection. Phylogenetic analysis with gymnosperm, angiosperm and bryophyte revealed the evolution of GSTs earlier than their division into separate groups and also prior to the divergence of monocot and dicot. The secondary structure prediction showed the dominance of α-helices indicative of PsomGSTs as structurally stable and elastic proteins. Gene architecture showed the conservation of number of exons across the classes. MEME analysis revealed only a few class specific and many across class conserved motifs. Ser was found to be the active site residue of tau, phi, theta and zeta class and Cys was catalytic residue of DHAR, lambda and GHR class. Promoter analyses identified many cis-acting regulatory elements related to hormonal, cellular, stress and light response functions. Ser was the key phosphorylation site. Only three glycosylation sites were found across the 93 PsomGSTs. 3D structure prediction was also performed and was validated. Interactome analyses revealed the correlation of PsomGSTs with glutathione metabolizing proteins. Gene enrichment analysis and KEGG pathway analyzed the involvement of PsomGSTs in three major pathways i.e. glutathione metabolism, tyrosine metabolism and ascorbate metabolism. The outcome revealed high model quality of PsomGSTs. The results of the current study will be of potential significance to understand the functional and structural importance of the GST gene family in opium, a medicinally important crop.

Serum levels of vitamin A, selenium, and better dietary total antioxidant capacity are related to lower oxidative DNA damage: A cross-sectional study of individuals at cardiovascular risk.

The risk for cardiovascular diseases (CVR) has been associated with oxidative DNA damage, but the genetic and environmental factors involved in the antioxidant and DNA repair system contributing to this damage are unknown. The aim was to evaluate the levels of oxidative DNA damage in CVR subjects and how it is related with some genetic and nutritional factors. The cross-sectional study evaluated 136 individuals of both sexes, aged 20-59 years, with at least one cardiovascular risk factor. The global risk score was used to classify individuals at low, intermediate, and high cardiovascular risk. The dietary total antioxidant capacity (DTAC) was calculated using table with FRAP values. The oxidative DNA damage was verified by the comet assay. The variants null of Glutathione-S-transferases Mu1 and Theta 1(GSTM1 and GSTT1) and rs25487 of X-Ray Repair Cross Complementing Protein 1 (XRCC1) were analyzed by real-time PCR and PCR-RFLP, respectively. The oxidative DNA damage was higher in patients with intermediate/high CVR than in patients with low CVR (P=.01). Individuals with GSTT1/GSTM1 null genotypes or arg/gln+gln/gln genotypes of the XRCC1 (rs25487) gene showed similar levels of oxidative DNA damage compared wild genotype. Multivariate regression analysis demonstrated that oxidative DNA damage in individuals with CVR depends on serum levels of vitamin A, selenium, and DTAC independently of the other factors [F(6.110)=8.213; P<.001; R2=0.330]. These findings suggest that nutritional factors such as DTAC, vitamin A and selenium may have a protective effect against oxidative DNA damage in these individuals.

Protocatechuic acid as a potent anticarcinogenic compound in purple rice bran against diethylnitrosamine-initiated rat hepatocarcinogenesis.

Our previous study demonstrated that purple rice bran extract (PRBE) could inhibit diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Protocatechuic acid (PCA) is the major phenolic acid contained in the PRBE. Therefore, this study aimed to determine whether PCA is an anticarcinogenic compound in purple rice extract. Rats were intraperitoneally injected with DEN to induce glutathione S-transferase placental form (GST-P)-positive foci. Rats were fed with PRBE at 500 mg kg-1 body weight or PCA at 4 mg kg-1 body weight for 5 and 15 weeks. PCA administration attenuated DEN-induced hepatic GST-P positive foci to a degree similar to PRBE. The molecular mechanisms of PCA in the initiation stage were correlated with reduced activity of cytochrome P450 reductase and induction of glutathione S-transferase. In addition, PCA also downregulated the expression of TNF-α and IL-1ß genes in rat liver. These genes are associated with the inhibition of inflammation. In the promotion stage, PCA suppressed cell proliferation correlated with the downregulation of Cyclin D1 expression. Moreover, it also induced apoptosis, indicated by increased expression of P53 and Bad genes, and decreased the expression of the anti-apoptotic Bcl-xl in DEN-initiated rats. These findings suggest that PCA is an active compound in the anticarcinogenic action of purple rice bran.

Genome-wide identification of glutathione S-transferase gene family members in tea plant (Camellia sinensis) and their response to environmental stress.

Glutathione S-transferases (GSTs) are ubiquitous enzymes involved in the regulation of plant growth, development, and stress responses. Unfortunately, the comprehensive identification of GSTs in tea plant has not been achieved. In this study, a total of 88 CsGSTs proteins were identified and divided into eight classes, among which the tau class was the largest. Chromosomal localization analysis revealed an uneven distribution of CsGSTs across the tea plant genome. Tandem duplication is the main force driving tea plant CsGSTs expansion. CsGSTs structures and conserved motifs were similar. The analysis of cis-regulatory elements in promoter regions showed that CsGSTs can response to multiple stresses, and that MYB may be involved in the transcriptional regulation of CsGST. RNA-Seq data revealed that the expression of most GSTUs was associated with various stresses, including pathogen and insect attack, cold spells, drought and salt stresses, nitrogen nutrition, bud dormancy, and morphological development, and the expression of these CsGSTs was obviously different in eight tissues. In addition, we proved that CsGSTU19, localized at the nucleus and cell membrane, was involved in tea plant defense against temperature stresses and Co. camelliae infection. These findings provide references for the further functional analysis of GSTs in the future.

Vitamin D3 supplementation alleviates chemically-induced cirrhosis-associated hepatocarcinogenesis.

Vitamin D3 (VD3) deficiency has been associated with increased risk for cirrhosis and hepatocellular carcinoma, a highly incident malignant neoplasia worldwide. On the other hand, VD3 supplementation has shown some beneficial effects in clinical studies and rodent models of chronic liver disease. However, preventive effects of dietary VD3 supplementation in cirrhosis-associated hepatocarcinogenesis is still unknow. To investigate this purpose, male Wistar rats submitted to a combined diethylnitrosamine- and thioacetamide-induced model were concomitantly supplemented with VD3 (5,000 and 10,000 IU/kg diet) for 25 weeks. Liver samples were collected for histological, biochemical and molecular analysis. Serum samples were used to measure 25-hydroxyvitamin D [25(OH)D] and alanine aminotransferase levels. Both VD3 interventions decreased hepatic collagen deposition and pro-inflammatory p65 protein levels, while increased hepatic antioxidant catalase and glutathione peroxidase activities and serum 25(OH)D, without a clear dose-response effect. Nonetheless, only the highest concentration of VD3 increased hepatic protein levels of VD receptor, while decreased the number of large preneoplastic glutathione-S-transferase- (>0.5 mm²) and keratin 8/18-positive lesions, as well the multiplicity of hepatocellular adenomas. Moreover, this intervention increased hepatic antioxidant Nrf2 protein levels and glutathione-S-transferase activity. In summary, dietary VD3 supplementation - in special the highest intervention - showed antifibrotic and antineoplastic properties in chemically-induced cirrhosis-associated hepatocarcinogenesis. The positive modulation of Nrf2 antioxidant axis may be mechanistically involved with these beneficial effects, and may guide future clinical studies.

Dietary inclusion of royal jelly modulates gene expression and activity of oxidative stress enzymes in zebrafish.

Here we investigated the effects of different levels of royal jelly in zebrafish (Danio rerio) diets [0.0% (D1); 0.1% (D2); 0.4% (D3); 1.6% (D4) vs 6.4% (D5)] on the activity and expression profiles of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione S-transferase. Muscle, liver and kidney tissue samples were obtained from fish fed during 8 weeks. In these tissues, enzyme activity was determined by means of spectrophotometer and gene expression by quantitative real-time PCR. mRNA levels of the enzymes were elevated in almost all diet groups compared to the control (D1). It was determined that enzyme activities were also increased in general by supplementation of royal jelly although some decreases were also observed. However, the significant correlation between gene expression and enzyme activity was not observed in all tissues. It was concluded that main regulation occurs with post-translational modifications although effects at transcriptomic level demonstrated a snap variation.

Quercetin ameliorates the hepatic apoptosis of foetal rats induced by in utero exposure to fenitrothion via the transcriptional regulation of paraoxonase-1 and apoptosis-related genes.

BACKGROUND & PURPOSE: Exposure to organophosphorus during different phases of pregnancy induces many adverse impacts on the developing foetuses due to their immature detoxification system. We have estimated the potential amelioration role of quercetin against hepatic injury-induced apoptosis in rat foetuses following gestational exposure to fenitrothion and probable involvement of paraoxonase-1. METHODS: Forty pregnant rats were allocated into four groups; the first one kept as control, the second intubated with quercetin (100 mg/kg), the third orally administrated fenitrothion (4.62 mg/kg) and the last group received quercetin two hours before fenitrothion intoxication. RESULTS: Fenitrothion significantly elevated the foetal hepatic levels of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide, but it reduced the enzymatic activities of glutathione-S-transferase, superoxide dismutase, catalase, and acetylcholinesterase. Furthermore, fenitrothion provoked many histopathological changes in the foetal liver and markedly up-regulated the mRNA gene expression of p53, caspase-9 along with elevation in the immunoreactivity of Bax and caspase-3, but it down-regulated the expression level of paraoxonase-1. Remarkably, quercetin co-treatment successfully ameliorated the hepatic oxidative injury and apoptosis prompted by fenitrothion. CONCLUSIONS: Dietary supplements with quercetin can be used to reduce the risk from organophosphorus exposure probably through paraoxonase-1 up-regulation and enhancement of the cellular antioxidant system.

Effect of lipoic acid supplementation on gene expression and activity of glutathione S-transferase enzyme in infertile men.

Oxidative stress has become the focus of interest as a potential cause of male infertility. We evaluate effects of lipoic acid (LA) supplementation on glutathione S-transferase (GST) expression. This randomized, triple-blind, placebo-controlled clinical trial was conducted on 44 infertile males with idiopathic asthenozoospermia. Men were randomized to receive 600 mg LA or placebo once daily for 12 weeks and semen samples and venous blood samples were obtained. GST expression, reactive oxygen species (ROS) levels, GST activity and reproductive hormone profiles were also measured. GST expression in the intervention group were significantly higher than the control group. Also, at the end of the study, GST activity increased, and ROS levels decreased significantly compared to the baseline. Additionally, the intervention group showed an increase in testosterone and decrease in serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin after 12 weeks, but this difference was not significant. We conclude a 12-week treatment with LA leads to improvements in reproductive hormones in serum, and significantly reduces the generation of ROS and increases the gene expression and activity of GST in seminal fluid.

The blood and mRNA levels of antioxidant-related factors in common carp (Cyprinus carpio) fed p-Coumaric acid.

The natural antioxidants are well known for their antioxidative activity without side effects when compared to antibiotics. Hence, the present study aimed at evaluating p-Coumaric acid as an antioxidant additive on the blood and mRNA levels of antioxidant-related factors in common carp (Cyprinus carpio). Fish fed the basal diet supplemented with p-Coumaric at 0, 0.5, 1, and 1.5 g/kg for 56 days, then the serum, intestine, and liver samples were collected. The growth performance of fish fed with CA showed significantly (P < 0.05) improved FW, WG, and SGR compared to those of the control one. However, the feed conversion ratio was significantly (P < 0.05) reduced in fish fed 1 and 1.5 g/kg diet levels. SOD was not significantly differed among the groups fed with varied p-Coumaric acid (P > 0.05). Serum GPX and TAC were enhanced considerably by p-Coumaric acid regarding the control with the highest being in fish fed 1.5 g/kg diet (P < 0.05). Serum CAT was more elevated in fish provided p-Coumaric acid at 1 or 1.5 g/kg than the control while fish fed 0.5 g/kg did not display significant changes. MDA level significantly decreased by all p-Coumaric acid groups compared to the control one, and the lowest level was observed in 1.5 g/kg (P < 0.05). The mRNA level of CAT was significantly upregulated in the liver by p-Coumaric acid at 1 or 1.5 g/kg (P < 0.05), while the intestine CAT did not influence by p-Coumaric acid (P > 0.05). The measured SOD in the liver and intestine samples revealed no changes in common carp fed p-Coumaric acid (P > 0.05). GPX was significantly upregulated in the intestine by p-Coumaric acid at 1 or 1.5 g/kg (P < 0.05), whereas the liver GPX was upregulated by p-Coumaric acid at 1.5 g/kg. The mRNA level of the GST gene in the intestine of common carp was upregulated by p-Coumaric acid at 1.5 g/kg, whereas the liver displayed upregulated GST in fish fed 1 g/kg diet. The present study approved the application of p-Coumaric acid as a natural antioxidant for friendly, sustainable aquaculture.

Neuroprotective effects of mango cv. 'Ataulfo' peel and pulp against oxidative stress in streptozotocin-induced diabetic rats.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis and progression of diabetes mellitus. Both can damage the brain. Mango and its by-products are sources of bioactive compounds with antioxidant properties. We hypothesized that mango cv. 'Ataulfo' peel and pulp mitigate oxidative stress in the brain of streptozotocin-induced diabetic rats. RESULTS: Twenty-four male Wistar rats were divided into four groups: control, untreated diabetic (UD), diabetic treated with a mango-supplemented diet (MTD), and diabetic pretreated with a mango-supplemented diet (MPD). The rats were fed the different diets for 4 weeks after diabetes induction (MTD), or 2 weeks before and 4 weeks after induction (MPD). After the intervention, serum and brain (cerebellum and cortex) were collected to evaluate gene expression, enzyme activity, and redox biomarkers. Superoxide dismutase 2 (SOD2) expression increased in the cortex of the MTD group, whereas glutathione-S-transferase p1 (GSTp1) expression was higher in the cortex of the MTD group, and cortex and cerebellum of the MPD group. SOD1 activity was higher in the cerebellum and cortex of all diabetic groups, whereas GST activity increased in the cerebellum and cortex of the MPD group. Lipid peroxidation increased in the cerebellum and cortex of the UD group; however, a mango-supplemented diet prevented this increase in both regions, while also mitigating polyphagia and weight loss, and maintaining stable glycemia in diabetic rats. CONCLUSION: We propose that mango exerts potent neuroprotective properties against diabetes-induced oxidative stress. It can be an alternative to prevent and treat biochemical alterations caused by diabetes. © 2020 Society of Chemical Industry.

Thiolatocobalamins repair the activity of pathogenic variants of the human cobalamin processing enzyme CblC.

Thiolatocobalamins are a class of cobalamins comprised of naturally occurring and synthetic ligands. Glutathionylcobalamin (GSCbl) occurs naturally in mammalian cells, and also as an intermediate in the glutathione-dependent dealkylation of methylcobalamin (MeCbl) to form cob(I)alamin by pure recombinant CblC from C. elegans. Glutathione-driven deglutathionylation of GSCbl was demonstrated both in mammalian as well as in C. elegans CblC. Dethiolation is orders of magnitude faster than dealkylation of Co-C bonded cobalamins, which motivated us to investigate two synthetic thiolatocobalamins as substrates to repair the enzymatic activity of pathogenic CblC variants in humans. We report the synthesis and kinetic characterization of cysteaminylcobalamin (CyaCbl) and 2-mercaptopropionylglycinocobalamin (MpgCbl). Both CyaCbl and MpgCbl were obtained in high purity (90-95%) and yield (78-85%). UV-visible spectral properties agreed with those reported for other thiolatocobalamins with absorbance maxima observed at 372 nm and 532 nm. Both CyaCbl and MpgCbl bound to wild type human recombinant CblC inducing spectral blue-shifts characteristic of the respective base-on to base-off transitions. Addition of excess glutathione (GSH) resulted in rapid elimination of the ß-ligand to give aquacobalamin (H2OCbl) as the reaction product under aerobic conditions. Further, CyaCbl and MpgCbl underwent spontaneous dethiolation thereby repairing the loss of activity of pathogenic variants of human CblC, namely R161G and R161Q. We posit that thiolatocobalamins could be exploited therapeutically for the treatment of inborn errors of metabolism that impair processing of dietary and supplemental cobalamin forms. While these disorders are targets for newborn screening in some countries, there is currently no effective treatment available to patients.

Senna plant generates reactive oxygen species (ROS) and induces apoptosis in Hymenolepis diminuta.

Like mammalian cells, helminth parasites are equipped with an array of enzymatic anti-oxidant system which has an adaptive strategy to cope up with several conditions of stress that arise from host immune response or drug treatment. Earlier, we had reported that three species of Senna, viz. S. alata, S. alexandrina and S. occidentalis leaf extracts caused severe morphological and biochemical alterations in the zoonotic parasite Hymenolepis diminuta. To understand whether the leaf extracts of the three species of Senna have any effect on the enzymatic anti-oxidant system in H.diminuta or not, the present study was investigated on the mechanism of action of these leaf extracts on the anti-oxidant system of the parasite. The viability of the parasite was assessed by MTT reduction assay, chromatin condensation through Hoechst staining of tissue and DNA fragmentation assay, and the oxidative enzymes of the parasite were estimated biochemically. Activity of superoxide dismutase, catalase, glutathione S- transferase and glutathione peroxidase were found to be increased in all the treated parasites from that of the control, with S. alata showed the highest increased amongst the three plant species in all the enzymes, at 331.0 %, 215.4 %, 85.4 % and 65.5 % respectively. Upliftment of apoptotic protein CED-3, CED-4 and EGL-1 and down regulation of anti-apototic protein CED-9 was visualised in all treated paraites. The redox imbalance triggered by these leaf extracts resulted in the activation of apoptotic pathway that led to death of the parasite. Our results demonstrated that the leaf extracts of the three Senna plant species could open new insight for an affordable natural anthelmintic with high efficacy and less toxicity.

Administration of grape (Vitis vinifera) seed extract to rainbow trout (Oncorhynchus mykiss) modulates growth performance, some biochemical parameters, and antioxidant-relevant gene expression.

Grape seed, as a main source of polyphenols, has many nutritional and medicinal properties in humans. In the current study, the effects of dietary ethanolic grape seed extract (GSE) on the growth performance, antioxidant activity, and some biochemical parameters in rainbow trout were investigated. Ninety fish (initial weight 78.47 g) were randomly distributed among nine cement tanks (1.8 m × 0.22 m × 0.35 m) with 10 fish per tank. Three experimental diets containing either 0, 10, or 50 g kg-1 GSE were prepared and each diet was randomly assigned to three tanks of fish for 60 days. Results showed that feeding GSE enhanced some growth parameters including the specific growth rate and condition factor in comparison with the control group. Among different serum metabolites, the glucose levels in treatment groups significantly decreased compared to the control group. The total product of lipid peroxidation indicated as malondialdehyde significantly decreased in both the GSE-added treatment groups. The gene expression related to the antioxidant enzymes, catalase, glutathione peroxidase 1, and glutathione S-transferase A, were upregulated in the intestine of fish that received a low dose of GSE. The results of the current study suggest that GSE, especially at 10 g kg-1, diet had the potential to improve (1) specific growth rate and condition factor, (2) biochemical parameters including glucose and lipid peroxidation product, and (3) upregulated the expression of antioxidant genes including catalase, glutathione peroxidase 1, and glutathione S-transferase A in rainbow trout.

Genomics of Detoxification: How Genomics can be Used for Targeting Potential Intervention and Prevention Strategies Including Nutrition for Environmentally Acquired Illness.

Due to their genomic variants, some individuals are more highly affected by toxicants than others. Toxicant metabolizing and activating variants have been linked with a wide variety of health issues including an increased risk of miscarriages, birth defects, Alzheimer's, benzene toxicity, mercury toxicity and cancer. The study of genomics allows a clinician to identify pathways that are less effective and then gives the clinician the opportunity to counsel their patients about diet, supplements and lifestyle modifications that can improve the function of these pathways or compensate to some extent for their deficits. This article will review a few of these critical pathways relating to phase I and phase 2 detox such as GSTP1, GPX1, GSTT1 deletions, PON1 and some of the CYP 450 system as examples of how an individual's genomic vulnerabilities to toxicants can be addressed by upregulating or downregulating specific pathways via genomically targeted use of foods, supplements and lifestyle changes.

Dietary vegetable choline improves hepatic health of Nile tilapia (Oreochromis niloticus) fed aflatoxin-contaminated diet.

Aflatoxin B1 (AFB1) is one of the most important mycotoxins due to its hepatotoxic and carcinogenic effects on animals. The effect of dietary supplementation with vegetable choline (VC) at 400, 800, and 1200 mg/kg against the deleterious effects of AFB1 (2 ppm/kg diet) in the liver of Nile tilapia (Oreochromis niloticus) was studied. The experimental period was 81 days, and the diet with VC was offered to the fish for 60 days prior to challenge with AFB1. Diets with AFB1 were tested in three replications and animals were analyzed at days 14 and 21 of dietary intake. The addition of VC to tilapia diet increased body weight (days 30 and 60 pre-challenge and day 21 post-challenge). The group fed aflatoxin-contaminated diet presented significantly reduced antioxidant enzymes and increased reactive oxygen species (ROS) levels, thiobarbituric acid reactive species (TBARS) levels, and protein carbonyl (PC) content in the liver. Dietary supplementation with VC at 800 and 1200 mg/kg demonstrated a significant protective effect, avoiding the increase of ROS, TBARS, and PC levels in the liver of tilapia from the aflatoxin contaminated groups. Thus, dietary VC supplementation may be used in tilapia to increase antioxidant status and reduce the negative effects caused by AFB1 toxicity. Based on the findings, it is recommended to use VC as a food supplement for Nile tilapia in order to avoid AFB1 toxication. In addition, decreased aflatoxin toxicity can be attributed to the VC antioxidant property.

Green tea polyphenol epigallocatechin-3-gallate improves the antioxidant capacity of eggs.

It has been shown that supplementation of layers' diets with epigallocatechin-3-gallate (EGCG) can improve egg albumen quality, but the underlying mechanisms behind this response are unclear. In this study, we investigate the effect of EGCG on egg antioxidative activity, free amino acid and fatty acid profiles, and the underlying relationship between the EGCG and oxidant-sensitive mitogen-activated protein kinase (MAPK) signaling pathway in laying hens. 288 hens (35-weeks-old) were fed 0 and 165 mg kg-1 of EGCG diets over 8 weeks. EGCG led to an increase in the albumen height, Haugh unit, and activity of glutathione S-transferase (GST) and a reduction in MDA content in plasma (P < 0.05). Egg white tryptophan and yolk carotenoid content was also increased by EGCG (P < 0.05). Eggs from EGCG fed layers had higher total antioxidant capacity (T-AOC), reducing power (RP), and oxygen radical absorbance capacity (ORAC), and lower albumen and yolk MDA content (P < 0.05). Also, liver gene and protein expression of P-38MAPK, nuclear factor erythroid 2-related 2 (Nrf2) and hemeoxygenase 1 (HO-1) was up-regulated by EGCG. Our findings suggest that dietary EGCG increased the antioxidant activity of eggs and regulated the MAPK/Nrf2 signaling pathway.

Lipidomics Provides Novel Insights into Understanding the Bee Pollen Lipids Transepithelial Transport and Metabolism in Human Intestinal Cells.

Bee pollen (BP) shows profound gut-protecting potentials. BP lipids (BPLs) mainly composed by phospholipids and polyunsaturated fatty acids might be one of the important contributors, while how BPL exerts gut-protecting effects and is transported through intestinal cell monolayers need to be investigated. Here, we exploited a strategy that combines an UPLC-Q-exactive orbitrap/MS-based lipidomics approach with a human intestinal cell (Caco-2) monolayer transport model, to determine the transepithelial transportation of BPL from Camellia sinensis L. (BPL-Cs), in pathological conditions. The results showed that BPL-Cs protected Caco-2 cells against dextran sulfate sodium (DSS)-induced intestinal barrier dysfunction by improving cell viability, maintaining membrane integrity, increasing tight junctions (ZO-1 and Claudin-1), and eliciting the expressions of antioxidative-related genes (NQO1, Nrf2, Txnrd1, and GSTA1). Lipidomics analysis revealed that DSS suppressed the transport and uptake of most of BPL-Cs including glycerophospholipids, sphingomyelins, and glycosylsphingolipids. Pretreatment with BPL-Cs significantly regulated glycerophospholipid and sphingolipid metabolisms, potentially involved in building permeability barriers and alleviating intestinal oxidative stress. Finally, eight classes of lipids were identified as the potential biomarkers for evaluating DSS-induced Caco-2 cell dysfunctions and BPL-intervened modulation. These findings shed light on the development of BPL as gastrointestinal protective food supplements in the future.