Inhibitory effect of metals on animal and plant glutathione transferases

Glutathione transferases (GSTs) represent a widespread enzyme superfamily in eukaryotes and prokaryotes catalyzing different reactions with endogenous and xenobiotic substrates such as organic pollutants. The latter are often found together with metal contamination in the environment. Besides performing of essential functions, GSTs protect cells by conjugation of glutathione with various reactive electrophiles. The interference of toxic metals with this functionality of GSTs may have unpredictable toxicological consequences for the organisms. In this review results from the recent literature are summarized and discussed describing the ability of metals to inhibit intracellular detoxification processes in animals and plants.     

Interleukin-1beta targets interleukin-6 in progressing dextran sulfate sodium-induced experimental colitis

Inflammatory bowel disease (IBD) is an immunologically mediated disorder that is characterized by chronic, relapsing, and inflammatory responses. Dextran sulfate sodium (DSS)-induced experimental colitis in mice has been recognized as a useful model for human IBD and interleukin (IL)-1beta is a key cytokine in the onset of IBD. The purpose of the present study was to clarify which pro-inflammatory mediators are targeted by IL-1beta in mice with DSS-induced colitis. First, we found that DSS markedly induced IL-1beta production in both dose- and time-dependent manners (P < 0.05 and P < 0.01, respectively) in murine peritoneal macrophages (pMphi), while that of tumor necrosis factor-alpha was insignificant. Further, the expressions of mRNA and protein for IL-1beta were increased in colonic mucosa and pMphi from mice that received drinking water containing 5% DSS for 7 days (P < 0.01, each). In addition, the expressions of IL-6, granulocyte macrophage-colony stimulating factor, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA were also time dependently increased (P < 0.01, each). Furthermore, administration of rIL-1beta (10 microg/kg, i.p.) significantly induced the expressions of IL-1beta and IL-6 mRNA in colonic mucosa from non-treated mice (P < 0.01). Anti-mIL-1beta antibody treatments (50 microg/kg, i.p.) attenuated DSS-induced body weight reduction and shortening of the colorectum (P < 0.05, each), and abrogated the expressions of IL-1beta and IL-6 mRNA in colonic mucosa (P < 0.01, each). Our results evidently support the previous findings that IL-1beta is involved in the development of DSS-induced experimental colitis in mice, and strongly suggest that IL-1beta targets itself and IL-6 for progressing colonic inflammation.     

Beneficial and preventive effect of chitin nanofibrils in a dextran sulfate sodium-induced acute ulcerative colitis model

Chitin nanofibrils, which are prepared from dried crab shells by a grinding method, are newly developed natural materials with uniform widths of approximately 10-20 nm. The bioactivities of chitin nanofibrils have not been investigated. In this study, we examined the preventive effects of chitin nanofibrils in a mouse model of dextran sulfate sodium (DSS)-induced acute ulcerative colitis. The results indicated that chitin nanofibrils improved clinical symptoms and suppressed ulcerative colitis. Furthermore, chitin nanofibrils suppressed myeloperoxidase activation in the colon and decreased serum interleukin-6 concentrations. Conversely, chitin powder did not suppress DSS-induced acute ulcerative colitis. Our results suggested that chitin nanofibrils have potential as a functional substance for inflammatory bowel disease patients.     

Distribution of glutathione transferases in Gram-positive bacteria and Archaea

Glutathione transferases (GSTs) have been widely studied in Gram-negative bacteria and the structure and function of several representatives have been elucidated. Conversely, limited information is available about the occurrence, classification and functional features of GSTs both in Gram-positive bacteria and in Archaea. An analysis of 305 fully-sequenced Gram-positive genomes highlights the presence of 49 putative GST genes in the genera of both Firmicutes and Actinobacteria phyla. We also performed an analysis on 81 complete genomes of the Archaea domain. Eleven hits were found in the Halobacteriaceae family of the Euryarchaeota phylum and only one in the Crenarchaeota phylum. A comparison of the identified sequences with well-characterized GSTs belonging to both Gram-negative and eukaryotic GSTs sheds light on their putative function and the evolutionary relationships within the large GST superfamily. This analysis suggests that the identified sequences mainly cluster in the new Xi class, while Beta class GSTs, widely distributed in Gram-negative bacteria, are under-represented in Gram-positive bacteria and absent in Archaea.     

小鼠溃疡性结肠炎模型的建立及病理组织学比较

目的建立乙酸,右旋葡聚糖硫酸钠（dextran sodium sulfate,DSS）,幽门螺杆菌（Helicobacter pyliri）小鼠溃疡性结肠炎（ulcerative colitis）动物模型,通过病理学对比观察,选择最佳的小鼠溃疡性结肠炎动物模型。方法将40只清洁级BALB/c小鼠随机分为4组,实验组中Ⅰ组采用乙酸刺激法诱发溃疡性结肠炎,Ⅱ组采用饮用3.5%DSS溶液诱发结肠炎,Ⅲ组采用幽门螺杆菌感染小鼠诱发溃疡性结肠炎,对照组饮用蒸馏水。观察小鼠每日的体重,大便性状和隐血情况,以及结肠大体形态和组织病理学改变。结果乙酸,右旋葡聚糖硫酸钠均可引起小鼠疡性结肠炎。结论 DSS诱发的小鼠溃疡性结肠炎是一种较理想的UC动物模型,可作为研究UC发病机制和药物治疗较理想的工具。     

Dietary quercetin ameliorates experimental colitis in mouse by remodeling the function of colonic macrophages via a heme oxygenase-1-dependent pathway

Inflammatory bowel disease (IBD) results from a chronic intestinal inflammation and tissue destruction via an aberrant immune-driven inflammatory response towards an altered gut microbiota. Dietary intervention is becoming an attractive avenue for the therapy of colitis because diet is a key determinant of the mucosal immune response. Quercetin (QCN) is the most common in nature and the major representative of dietary antioxidant flavonoids, which has been demonstrated to influence the progression of colitis. However, the underlying mechanism of QCN on intestinal immunomodulation remains unclear. Here, our study demonstrated dietary QCN could ameliorate experimental colitis in part by modulating the anti-inflammatory effects and bactericidal capacity of macrophages via Heme oxygenase-1 (Hmox1, HO-1) dependent pathway. It suggested that QCN might restore the proper intestinal host-microbe relationship to ameliorate the colitis via rebalancing the pro-inflammatory, anti-inflammatory and bactericidal function of enteric macrophages. Hence, modulating the function of intestinal macrophages with dietary administration of QCN to restore the immunological hemostasis and rebalance the enteric commensal flora is a potential and promising strategy for IBD therapy.     

Regulation of Toll-like receptor 4 expression in mouse colon by macrophage migration inhibitory factor

Recent studies have indicated that macrophage migration inhibitory factor (MIF) and Toll-like receptor (TLR) play an important role in the regulation of innate immune responses. In this study, we investigated the effect of MIF on the expression of TLR4, a receptor that recognizes lipopolysaccharide, in colon using MIF-deficient mice. TLR4 mRNA expression in the colon tissues was determined by northern blot analysis. Western blot analysis and immunohistochemistry in the colon tissues were performed to evaluate the expression of TLR4 protein. The expressions of TLR4 mRNA and protein were remarkably down-regulated in colon tissues of MIF-deficient mice compared with wild-type mice and up-regulated by treatment with recombinant MIF. Immunohistochemical study revealed the presence of TLR4–positive staining in mononuclear cells in the lamina propria and intraepithelial mononuclear cells as well as weak staining in epithelial cells and crypts in colon tissues of wild-type mice. In contrast, MIF-deficient mice did not show TLR4-positive staining in the colonic mucosa. In MIF-deficient mice injected with recombinant mouse MIF (rMIF), TLR4-positive staining cells were observed in colon tissues similar to the findings in wild-type mice. Administration of dextran sulfate sodium (DSS) up-regulated the expression of TLR4 in the colons of WT mice but not in those of MIF-deficient mice. Furthermore, pretreatment with rMIF up-regulated the expression of TLR4 in response to DSS in MIF-deficient mice. Our results suggest that MIF affects the expression of TLR4 in mouse colon under both normal and colitic conditions.An erratum to this article can be found at     

CD11b在小鼠急性结肠炎模型中的表达及鼠李糖乳杆菌的调节作用

目的 研究CD11b在炎症性肠病模型小鼠结肠组织中的表达及定位,探讨鼠李糖乳杆菌(LGG)对CD11b的调节作用.方法 将28只SPF级小鼠随机分为3组:Ctrl组8只、DSS组10只、DSS+LGG组10只,给予3％ DSS自由饮用建立急性结肠炎模型,DSS+ LGG组小鼠提前1周管饲LGG共14 d;模型建立期间观...     

肠道菌群分析及粪便炎性标志物检测在炎症性肠病活动度评估中的作用

目的 探讨肠道菌群和粪便炎性标志物在炎症性肠病（IBD）活动度评估中的临床价值。方法 共纳入120例IBD患者为研究组,其中溃疡性结肠炎（UC）患者68例,克罗恩病（CD）患者52例。选择30例经结肠镜检查正常的健康体检者为对照组。采集全部研究对象的新鲜粪便标本进行粪便细菌培养及炎性标志物检测,比较不同疾病活动度IBD患者的肠道菌群及粪便钙卫蛋白（FC）、乳铁蛋白（LF）、基质金属蛋白酶-9（MMP-9）、髓过氧化酶（MPO）水平的变化。结果 与对照组比,UC和CD患者肠道中肠杆菌、肠球菌、拟杆菌、消化球菌及酵母菌数量均明显增加（P＜0.05）,双歧杆菌、乳杆菌及真杆菌数量明显减少（P＜0.05）。UC患者梭菌数量较对照组增加（P＜0.05）,CD患者梭菌数量较对照组减少（P＜0.05）。UC、CD活动期患者肠杆菌、肠球菌、拟杆菌、消化球菌及酵母菌数量明显多于缓解期患者（P＜0.05）,双歧杆菌、乳杆菌及真杆菌数量明显少于缓解期患者（P＜0.05）,且重度活动期患者肠道菌群改变较轻、中度活动期改变更明显（P＜0.05）。UC活动期患者梭菌数量明显多于缓解期（P＜0.05）,CD活动期患者梭菌数量明显少于缓解期（P＜0.05）。UC和CD患者粪便中FC、LF、MMP-9及MPO水平均显著高于对照组（P＜0.05）。UC、CD活动期患者FC、LF、MMP-9及MPO水平显著高于缓解期患者（P＜0.05）,且重度活动期患者高于轻、中度活动期患者（P＜0.05）。结论 肠道菌群变化和粪便中FC、LF、MMP-9及MPO水平可作为IBD患者疾病活动性评估的辅助指标。     

Molecular evidences on the benefit of N-acetylcysteine in experimental colitis

Inflammatory bowel disease (IBD) is a chronic recurrent disease of the digestive tract with an unknown etiology. The aim of this study was to examine the possible protective effects of N-acetylcysteine (NAC) in the mouse model of IBD by measuring specific biomarkers in the colon cells. Colitis was induced by administration of dextran sodium sulfate (DSS) in drinking water (3%) for 7 days. Three doses of NAC (106, 160, and 240 mg/kg) were given after induction of colitis (4 days post DSS) for 4 days by gavage. Lipid peroxides (LP), total antioxidant power (TAP), total thiol molecules (TTM), tumor necrosis factor-α (TNF-α), nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT) were measured in the colon homogenate of the treated animals. NAC (160 and 240 mg/kg) significantly decreased LP, TNF-α, NO and increased TTM, SOD, and CAT. The TAP was also increased by NAC (240 mg/kg). It is concluded that moderate to high doses of NAC improves cellular biomarkers of IBD in mice. Further studies should be trialled in humans suffering from two common inflammatory bowel disease called ulcerative colitis and Crohn’s disease.     

粪菌移植治疗肠易激综合征研究进展

粪菌移植(faecal microbiota transplantation,FMT)是将从健康供体获得的粪便悬液转移至患者消化道,从而恢复肠道正常微生物组成和功能的一种治疗方法。近年来,FMT治疗肠易激综合征(irritable bowel syndrome,IBS)的疗效和经济效益越来越受到研究者的重视。这种方法已经成为艰难梭菌感染(Clostridium difficile infection,CDI)的成熟替代疗法。此外,FMT还在炎症性肠病(inflammatory bowel disease,IBD)和胃肠疾病以外的疾病,如心血管疾病、自身免疫性疾病和代谢综合征等多种疾病的治疗中取得了显著进展。关于FMT仍有许多未解的问题,需要在这一领域进行更多研究。本文就IBS的发病机制、FMT的疗效和安全性进行综述。     

Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A

Orexins (orexin-A and orexin-B) are hypothalamic peptides that are produced by the same precursor and are involved in sleep/wake control, which is mediated by two G protein-coupled receptor subtypes, OX1R and OX2R. Ulcerative colitis (UC) is an inflammatory bowel disease, (IBD) which is characterized by long-lasting inflammation and ulcers that affect the colon and rectum mucosa and is known to be a significant risk factor for colon cancer development. Based on our recent studies showing that OX1R is aberrantly expressed in colon cancer, we wondered whether orexin-A could play a role in UC. Immunohistochemistry studies revealed that OX1R is highly expressed in the affected colonic epithelium of most UC patients, but not in the non-affected colonic mucosa. Injection of exogenous orexin-A specifically improved the inflammatory symptoms in the two colitis murine models. Conversely, injection of inactive orexin-A analog, OxB7–28 or OX1R specific antagonist SB-408124 did not have anti-inflammatory effect. Moreover, treatment with orexin-A in DSS-colitis induced OX1R^?/? knockout mice did not have any protective effect. The orexin-A anti-inflammatory effect was due to the decreased expression of pro-inflammatory cytokines in immune cells and specifically in T-cells isolated from colonic mucosa. Moreover, orexin-A inhibited canonical NFκB activation in an immune cell line and in intestinal epithelial cell line. These results suggest that orexin-A might represent a promising alternative to current UC therapies.     

Correlation of neutrophil and monocyte derived interleukin-1 receptor antagonist and interleukin-8 with colitis severity in the rabbit

Activated neutrophils and monocytes produce interleukin (IL)-8, a pro-inflammatory chemokine, but also IL-1 receptor antagonist (IL-1ra), which is an anti-inflammatory cytokine. We were interested to see the profiles of IL-8 and IL-1ra in the colonic tissue and in the peripheral blood leukocytes (PBL) during the development of immune complex induced colitis in rabbits. IL-1ra and IL-8 in PBL were measured in 26 rabbits at time 0 h, 24 h, and 48 h after induction of colitis. The colons were removed at 48 h for measuring myeloperoxidase (MPO), ulcer area, IL-1ra and IL-8. Epithelial damage, crypt abscess formation and leukocyte infiltration of the colonic tissue were major features of this colitis model. During the development of colitis, there was an increase in circulating neutrophils and monocytes (P < 0.0001), but not lymphocytes. Likewise, elevated amounts of IL-1ra (P = 0.0001) and IL-8 (P = 0.0219) production by PBL were observed following induction of colitis. Flow cytometry revealed major source of IL-1ra was monocytes, while the main sources of IL-8 were neutrophils and monocytes. There was correlation between MPO and ulcer area (R_s = 0.6327, P < 0.0001). At 24 h, PBL from MPO^High group (n = 11) showed increased IL-1ra (P = 0.027) and IL-8 (P = 0.0128) levels vs MPO^Low group (n = 15). IL-8 production by PBL showed correlation with tissue MPO (R_s = 0.4273, P = 0.0295). The colitis in this model was associated with an increase in circulating monocytes and neutrophils, which released increased amounts of IL-8 and IL-1ra. Further, IL-8 and IL-1ra showed correlation with the severity of colitis. These observations should significantly further understandings on the role of neutrophils and monocytes in the immunopathogenesis of ulcerative colitis.     

The effect of intestinal alkaline phosphatase on intestinal epithelial cells,macrophages and chronic colitis in mice

Aims

Intestinal alkaline phosphatase (IAP) is an intestinal brush border enzyme that is shown to function as a gut mucosal defense factor, but its defensive mechanism remains unclear. The aims of this study were to evaluate the effect of IAP on intestinal epithelial cells and macrophages, and on chronic colitis in interleukin-10-deficient (IL-10^−/−) mice.

Main methods

Human intestinal epithelial cells COLO 205 and peritoneal macrophages from IL-10^−/− mice were pretreated with IAP and then stimulated with lipopolysaccharide (LPS). IL-8 secretion from COLO205 cells and TNF-α, IL-6, IL-12 from peritoneal macrophages were measured by ELISA. Electrophoretic mobility shift assay was used to assess the DNA binding activity of NF-κB and IκBα phosphorylation/degradation was evaluated by immunoblot assay in COLO 205. For the in vivo study, colitis was induced in IL-10^−/− mice with piroxicam, the mice were then treated with 100 or 300 units of IAP by oral gavage for 2 weeks. Colitis was quantified by histopathologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry.

Key findings

IAP significantly inhibited LPS-induced inflammatory cytokine production in both IECs and peritoneal macrophages. IAP also attenuated LPS-induced NF-κB binding activity and IκBα phosphorylation/degradation in IECs. Oral administration of IAP significantly reduced the severity of colitis and down-regulated colitis-induced IκBα phosphorylation in IL-10^−/− mice.

Significance

IAP may inhibit the activation of intestinal epithelial cells and peritoneal macrophages, and may attenuate chronic murine colitis. This finding suggests that IAP supplementation is a potential therapeutic option for inflammatory bowel disease.     

Role of Se-dependent glutathione peroxidases in gastrointestinal inflammation and cancer

Increase in reactive oxygen species plays an integral part in the inflammatory response, and chronic inflammation increases cancer risk. Selenium-dependent glutathione peroxidase (GPX) is well recognized for its antioxidant, and thus anti-inflammatory, activity. However, due to the multiple antioxidant families present in the gastrointestinal tract, it has been difficult to demonstrate the importance of individual antioxidant enzymes. Using genetically altered mice deficient in individual Gpx genes has provided insight into the physiological functions of these genes. Insufficient GPX activity in the mucosal epithelium can trigger acute and chronic inflammation. The presence of certain microflora, such as Helicobacter species, may affect cancer risk significantly. However, when damaged cells have progressed into a precancerous status, increased GPX activity may become procarcinogenic, presumably due to inhibition of hydroperoxide-mediated apoptosis. This review summarizes the current view of GPX in inflammation and cancer with emphasis on the GI tract.     

N‐nitrosodimethylamine changes the expression of glutathione S‐transferase in the liver of male mice: The role of antioxidants

The present study investigated the protective effect of gossypol, selenium, zinc, or glutathione (GSH) against dimethylnitrosamine (DMN)‐induced hepatotoxicity in the livers of male mice. The expression and the activity of glutathione S‐transferase (GST), levels of GSH, and free radicals (malondialdehyde (MDA)), as well as the activity of glutathione reductase were determined after the treatment of mice for seven consecutive days with low or high doses of gossypol, selenium, zinc, or GSH. In experimental groups, DMN was administered as a single dose for 2 h after the repeated dose treatments of mice for seven consecutive days with each antioxidant. DMN reduced the expression and inhibited the activity of GST. However, repeated treatments of mice with low‐dose gossypol or high dose of either selenium or GSH followed by a single dose of DMN induced the expression and the activity of GST. In contrast, low‐dose treatments of mice with zinc, selenium, or GSH followed by a single dose of DMN reduced the expression and the activity of GST compared to either control or DMN‐treated groups. In addition, high‐dose treatment with either gossypol or selenium markedly induced the levels of GSH compared to either control or DMN‐treated groups. Interestingly, pretreatment of mice with high dose of either gossypol or selenium for seven consecutive days followed by a single dose of DMN decreased the levels of MDA, whereas DMN induced such levels. It is concluded that high dose of either gossypol or selenium is a stronger protector than zinc and GSH in ameliorating the toxic effects of DMN. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:389–395, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20255     

The role of the Aedes aegypti Epsilon glutathione transferases in conferring resistance to DDT and pyrethroid insecticides

The Epsilon glutathione transferase (GST) class in the dengue vector Aedes aegypti consists of eight sequentially arranged genes spanning 53,645 bp on super contig 1.291, which maps to chromosome 2. One Epsilon GST, GSTE2, has previously been implicated in conferring resistance to DDT. The amino acid sequence of GSTE2 in an insecticide susceptible and a DDT resistant strain differs at five residues two of which occur in the putative DDT binding site. Characterization of the respective recombinant enzymes revealed that both variants have comparable DDT dehydrochlorinase activity although the isoform from the resistant strain has higher affinity for the insecticide. GSTe2 and two additional Epsilon GST genes, GSTe5 and GSTe7, are expressed at elevated levels in the resistant population and the recombinant homodimer GSTE5-5 also exhibits low levels of DDT dehydrochlorinase activity. Partial silencing of either GSTe7 or GSTe2 by RNA interference resulted in an increased susceptibility to the pyrethroid, deltamethrin suggesting that these GST enzymes may also play a role in resistance to pyrethroid insecticides.     

溃疡性结肠炎患者肠道菌群和肠黏膜屏障的变化及益生菌的干预作用

目的 探讨溃疡性结肠炎（UC）患者肠道菌群和肠黏膜屏障的变化及益生菌的干预作用。方法 选取2014年1月—2017年12月内科门诊就诊活动期UC患者50例为观察组,予以双歧杆菌三联活菌胶囊2粒/次（210 mg/粒）,饭后30 min温水送服,2次/d,连用8周。检测观察组治疗前与治疗后肠道菌群数量及肠黏膜屏障指标的变化。另选择同期肠镜检查未见肠道病变的正常成人30例为对照组。结果 观察组患者治疗前双歧杆菌和乳酸杆菌的数量明显少于对照组,而大肠杆菌数量明显多于对照组（Ps<0.05）。治疗8周后,观察组患者双歧杆菌和乳酸杆菌的数量较治疗前明显上升（Ps<0.05）,但仍明显低于对照组（Ps<0.05）;而大肠杆菌数量较前明显下降（Ps<0.05）,但仍明显高于对照组（Ps<0.05）。同时观察组患者治疗前血清ET、D-乳酸和PCT水平明显高于对照组（Ps<0.05）。治疗8周后,血清ET、D-乳酸和PCT水平较治疗前明显下降（Ps<0.05）,但仍明显高于对照组（Ps<0.05）。结论 双歧杆菌三联活菌胶囊治疗活动性UC能纠正患者肠道菌群紊乱,修复肠黏膜屏障。     

On the benefits of silymarin in murine colitis by improving balance of destructive cytokines and reduction of toxic stress in the bowel cells

Inflammatory bowel disease (IBD) is a multifactorial disease with an unknown etiology characterized by oxidative stress, leucocyte infiltration and a rise in inflammatory cytokines. In this study, we have investigated the effects of silymarin, a mixture of several flavonolignans with established antioxidant and anti-inflammatory properties, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced in male Wistar-albino rats by delivering TNBS to the distal colon. All the medicines were administered by gavage for seven days. Thirty-six male rats were divided into six groups containing six rats in each one. Control rats received only TNBS. In the treated groups, animals were given different doses of silymarin (40, 80, and 160 mg/kg). Dexamethasone (1 mg/kg) was used as the positive treatment. Colonic status was investigated seven days post induction of colitis through macroscopic, histological, and biochemical analyses. Amelioration of the morphological signs including macroscopic damage, necrotic area, and histology were seen subsequent to treating animals with silymarin. These observations were accompanied by a significant reduction in the degree of both neutrophil infiltration, indicated by decreased myeloperoxidase activity, and lipid peroxidation, as measured by a decline in malodialdehyde content in inflamed colon as well as a decrease in levels of inflammatory cytokines (TNF-α and IL-1β). The results of the present study reveal that the beneficial effect of silymarin in bowel cells is mediated through its anti-oxidant and anti-inflammatory potentials.     

Effects of Se-depletion on glutathione peroxidase and selenoprotein W gene expression in the colon

Selenium (Se)-containing proteins have important roles in protecting cells from oxidative damage. This work investigated the effects of Se-depletion on the expression of the genes encoding selenoproteins in colonic mucosa from rats fed diets of different Se content and in human intestinal Caco-2 cells grown in Se-adequate or Se-depleted culture medium. Se-depletion produced statistically significant (P<0.05) falls in glutathione peroxidase (GPX) 1 mRNA (60-83%) and selenoprotein W mRNA (73%) levels, a small but significant fall in GPX4 mRNA (17-25%) but no significant change in GPX2. The data show that SelW expression in the colon is highly sensitive to Se-depletion.