The Pathogenicity of an EntericCitrobacter rodentiumInfection Is Enhanced by Deficiencies in the Antioxidants Selenium and Vitamin E

ABSTRACTThe pathogenesis of aCitrobacter rodentiuminfection was evaluated in mice fed diets with a single deficiency in either selenium or vitamin E or with a double deficiency in both selenium and vitamin E compared to mice on nutritionally adequate diets. Mice fed the selenium- and vitamin E-deficient diet for 6 weeks had increased loads ofC. rodentiumin the colon and spleen, which were not observed in mice fed either of the singly deficient diets or the adequate diet. Infected mice fed the doubly deficient diet had increased colon crypt hyperplasia and an influx of infiltrating cells along with gross changes to crypt architecture, including ulceration and denuding of the epithelial layer. Cytokine and chemokine mRNA levels in the colon were measured by real-time PCR. Expression of proinflammatory cytokines and chemokines was upregulated on day 12 after infection withC. rodentiumin mice fed the doubly deficient diet compared to mice fed the control diet. Heme oxygenase 1, an enzyme upregulated by oxidative stress, also was more highly induced in infected mice fed the doubly deficient diet. Production ofC. rodentiumantigen-specific IgM and IgG antibodies was not affected by feeding the doubly deficient diet. The results indicated that selenium and vitamin E play an important role in host resistance and in the pathology induced byC. rodentium, an infection that mimics disease caused by common food-borne bacterial pathogens in humans.

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Effect of Heme Oxygenase-1 Overexpression in Two Models of Lung Inflammation

Experimental Biology and Medicine ◽

10.1177/15353702-0322805-02 ◽

2003 ◽

Vol 228 (5) ◽

pp. 442-446 ◽

Cited By ~ 49

Author(s):

A. Zampetaki ◽

T. Minamino ◽

S.A. Mitsialis ◽

S. Kourembanas

Keyword(s):

Transgenic Mice ◽

Heme Oxygenase ◽

Lung Inflammation ◽

Heme Oxygenase 1 ◽

Mrna Levels ◽

Wild Type ◽

Pronounced Increase ◽

Protein Levels ◽

Cytokines And Chemokines ◽

Genetically Engineered Mice

An increasing number of studies implicate heme oxygenase-1 (HO-1) in the regulation of inflammation. Although the mechanisms involved in this cytoprotection are largely unknown, HO-1 and its enzymatic products, carbon monoxide and bilirubin, downregulate the inflammatory response by either attenuating the expression of adhesion molecules and thus inhibiting leukocyte recruitment or by repressing the induction of cytokines and chemokines. In the present study we used genetically engineered mice that express high levels of a human cDNA HO-1 transgene in lung epithelium to assess the effect of HO-1 on lung inflammation. Two separate models of inflammation were studied: hypoxic exposure and lipopolysaccharide (LPS) challenge. We found that both mRNA and protein levels of specific cytokines and chemokines were significantly elevated in response to hypoxia in the lungs of wild-type mice after 2 and 5 days of exposure but significantly suppressed in the hypoxic lungs of transgenic mice, suggesting that inhibition of these cytokines was caused by overexpression of HO-1. However, LPS treatment resulted in a very pronounced increase in mRNA levels of several cytokines in both wild-type and transgenic mice. Despite the high mRNA levels, significantly lower cytokine protein levels were detected in the bronchoalveolar lavage of HO-1 overexpressing mice compared with wild type, indicating that HO-1 leads to repression of cytokines in the airway. These results demonstrate that HO-1 activity operates through distinct molecular mechanisms to confer cytoprotection in the hypoxic and the LPS models of inflammation.

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Vitamin E Deficiency Fails to Affect Myocardial Performance During In Vivo Ischemia-Reperfusion

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.70.6.293 ◽

2000 ◽

Vol 70 (6) ◽

pp. 293-300 ◽

Cited By ~ 8

Author(s):

Jeff Coombes ◽

Scott Powers ◽

Haydar Demirel ◽

Karyn Hamilton ◽

James Jessup ◽

...

Keyword(s):

Vitamin E ◽

Corn Oil ◽

Ischemia Reperfusion ◽

Control Diet ◽

Cardiac Performance ◽

In Vivo Model ◽

Vitamin E Deficiency ◽

Deficient Diet ◽

Protein Thiols

Vitamin E content, of cardiac tissue, has been proposed to play a major, role in the damage caused by myocardial ischemia-reperfusion (I-R). Previous studies using in vitro models have examined vitamin E deficiency and I-R-induced myocardial damage with equivocal results. The purpose of this study was to use an in vivo model of myocardial I-R to determine the effects of vitamin E deficiency on myocardial I-R-induced damage. Female Sprague-Dawly rats (4-mo old) were assigned to either: 1) control diet (CON), or 2) vitamin E deficient diet (VE-DEF). The CON diet was prepared to meet AIN-93M standards, which contains 75 IU vitamin E/kg diet. The VE-DEF diet was the AIN-93M diet prepared with tocopherol stripped corn oil and no vitamin E. Following a 14-week feeding period, significant differences (p < 0.05) existed in mean myocardial VE levels between groups (mean values ± SEM: CON = 48.2 ± 3.5; VE-DEF = 12.4 ± 1,4 mug VE/g wet weight). Animals from both experimental groups were subjected to an in vivo I-R protocol consisting of 25 minutes of left coronary artery occlusion followed by 10 minutes of reperfusion. No group differences (p > 0.05) existed in cardiac performance (peak arterial pressure or ventricular work) or the incidence of ventricular arrhythmias during the I-R protocol. VE-DEF animals had significantly higher (p < 0.05) levels of myocardial lipid peroxidation and lower (p < 0.05) protein thiols following I-R compared to the CON animals. These data suggest that although vitamin E deficiency increases oxidative damage resulting from myocardial I-R, it does not affect cardiac performance during the insult.

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Magnesium and calcium deficiencies additively increase zinc concentrations and metallothionein expression in the rat liver

British Journal Of Nutrition ◽

10.1017/s0007114512001195 ◽

2012 ◽

Vol 109 (3) ◽

pp. 425-432 ◽

Cited By ~ 7

Author(s):

Megumi Kotani ◽

Ki Hyun Kim ◽

Natsumi Ishizaki ◽

Masayuki Funaba ◽

Tohru Matsui

Keyword(s):

Rat Liver ◽

Control Diet ◽

Mrna Level ◽

Male Rats ◽

Mrna Levels ◽

Deficient Diet ◽

Mg Deficiency ◽

Ca Deficiency ◽

Zn Concentration ◽

Dietary Treatments

Mg deficiency increases the concentration of Zn in the liver. We investigated the effect of Mg deficiency on the expression of Zn-regulating factors such as Zn transporters and metallothionein (MT) in the rat liver. Because Ca deficiency alleviates some of the effects of Mg deficiency, we also investigated the interactions associated with Ca and Mg deficiencies. Growing male rats were given a control diet, a Mg-deficient diet, a Ca-deficient diet and a Mg- and Ca-deficient diet for 3 weeks. Mg and Ca deficiencies additively increased the mRNA levels of MT-1 and MT-2, the MT protein concentration and the concentration of Zn in the liver. The hepatic mRNA level of Zip14 increased with Mg deficiency but not with Ca deficiency. The dietary treatments did not affect the mRNA levels of other Zn transporters such as Zip1, Zip5, ZnT1, ZnT5 and ZnT6 in the liver. Ca deficiency was found to decrease the amount of femoral Zn and increase serum Zn concentration. This did not occur in the case of Mg deficiency. These results suggest that Mg deficiency enhances hepatic Zn uptake by the up-regulation of Zip14 expression and increases hepatic Zn concentration, leading to the enhancement of MT expression. Ca deficiency causes a transfer of Zn from the bone to the liver, which increases hepatic Zn concentration and, in turn, up-regulates the expression of MT. Because Mg and Ca deficiencies increase hepatic Zn concentration and increase MT expression by different mechanisms, their effects are additive.

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Electrodiagnosis of vitamin E-deficient and denervated skeletal muscle of rabbits

Journal of Applied Physiology ◽

10.1152/jappl.1960.15.4.671 ◽

1960 ◽

Vol 15 (4) ◽

pp. 671-676 ◽

Cited By ~ 3

Author(s):

John J. Fudema ◽

Yvo T. Oester ◽

James A. Fizzell ◽

Arthur J. Gatz

Keyword(s):

Vitamin E ◽

Motor Nerve ◽

Control Diet ◽

Denervated Muscle ◽

Upward Trend ◽

Dystrophic Muscle ◽

Deficient Diet ◽

Complete Section ◽

Anterior Tibial ◽

Late Stages

Nutritional muscular dystrophy was produced in rabbits maintained on a vitamin E-deficient diet. Electrodiagnostic data collected from the anterior tibial muscles of these animals were compared with data from control animals on the same diet supplemented with vitamin E, and animals on the control diet which had unilateral surgical denervation of one anterior tibial muscle. Strength-duration curves of muscles developing dystrophy demonstrated a pronounced upward trend and were complex, containing two segments with a discontinuity at their juncture. This upward trend and the discontinuity of the strength-duration curves suggest the presence of denervation, for these are characteristically found in muscle denervated by partial or complete section of the motor nerve. Chronaxie, repetitive stimulation and galvanic tetanus ratio values of dystrophic muscle in the late stages were found to be comparable to the observations of the same criteria in the early stages of denervated muscle. No change in threshold of vitamin E-deficient muscle to faradic stimulation was found. In denervated muscle, response to faradic stimulation persisted, though with increased threshold at the end of a 60-day observation period. Submitted on December 9, 1959

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Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16659498 ◽

2016 ◽

Vol 37 (6) ◽

pp. 2035-2048 ◽

Cited By ~ 25

Author(s):

Kah Ni Tan ◽

Catalina Carrasco-Pozo ◽

Tanya S McDonald ◽

Michelle Puchowicz ◽

Karin Borges

Keyword(s):

Control Diet ◽

Atp Synthesis ◽

Decanoic Acid ◽

Basal Respiration ◽

Heme Oxygenase 1 ◽

Mrna Levels ◽

Plasma Antioxidant Capacity ◽

Seizure Models ◽

Plasma Antioxidant ◽

Beta Hydroxybutyrate

The hypothesis that chronic feeding of the triglycerides of octanoate (trioctanoin) and decanoate (tridecanoin) in “a regular non-ketogenic diet” is anticonvulsant was tested and possible mechanisms of actions were subsequently investigated. Chronic feeding of 35E% of calories from tridecanoin, but not trioctanoin, was reproducibly anticonvulsant in two acute CD1 mouse seizure models. The levels of beta-hydroxybutyrate in plasma and brain were not significantly increased by either treatment relative to control diet. The respective decanoate and octanoate levels are 76 µM and 33 µM in plasma and 1.17 and 2.88 nmol/g in brain. Tridecanoin treatment did not alter the maximal activities of several glycolytic enzymes, suggesting that there is no reduction in glycolysis contributing to anticonvulsant effects. In cultured astrocytes, 200 µM of octanoic and decanoic acids increased basal respiration and ATP turnover, suggesting that both medium chain fatty acids are used as fuel. Only decanoic acid increased mitochondrial proton leak which may reduce oxidative stress. In mitochondria isolated from hippocampal formations, tridecanoin increased respiration linked to ATP synthesis, indicating that mitochondrial metabolic functions are improved. In addition, tridecanoin increased the plasma antioxidant capacity and hippocampal mRNA levels of heme oxygenase 1, and FoxO1.

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Curcumin Inhibits Acute Vascular Inflammation through the Activation of Heme Oxygenase-1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/3295807 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Yunjun Xiao ◽

Junjie Xia ◽

Shuang Wu ◽

Ziquan Lv ◽

Suli Huang ◽

...

Keyword(s):

Carotid Artery ◽

Heme Oxygenase ◽

Control Diet ◽

Vascular Inflammation ◽

Heme Oxygenase 1 ◽

Mrna Levels ◽

Anti Inflammatory ◽

Inflammatory Effect

Curcumin has several therapeutic properties such as anti-inflammatory effect. Heme oxygenase-1 (HO-1) has been showed to have cytoprotective effects in some pathological conditions. However, the role of HO-1 in anti-inflammatory effect of curcumin is unknown. In this study, we investigate whether the anti-inflammatory effect of curcumin in vascular may be involved in the activation of HO-1. New Zealand white rabbits were fed regular control diet or control diet added with 0.3% curcumin (wt/wt) for four weeks. Acute vascular inflammation of rabbits was induced by putting a collar on the left common carotid artery for 24 hours. HO-1 inhibitor and siRNA were used to investigate the role of HO-1 in the anti-inflammatory effect of curcumin in collared vascular. We also explored the mechanism of curcumin-induced activation of HO-1 in vitro. The serum bilirubin and vascular, liver, and spleen HO-1 mRNA levels were significantly increased in curcumin-treated rabbits. The vascular inflammation was significantly decreased in the curcumin-treated animals compared with the control. Treatment of the rabbits with an inhibitor of HO or HO-1 siRNA to knock down the carotid artery HO-1 abolished the ability of curcumin to inhibit vascular inflammation. Treatment of cultured human artery endothelial cells with curcumin induced the HO-1 expression through the activation of nuclear factor-E2-related factor 2 (Nrf2) and an antioxidant responsive element via the p38 MAPK signalling pathway. In conclusion, curcumin inhibits vascular inflammation in vivo and in vitro through the activation of HO-1.

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Fluctuations in metabolite content in the liver of magnesium-deficient rats

British Journal Of Nutrition ◽

10.1017/s0007114516003676 ◽

2016 ◽

Vol 116 (10) ◽

pp. 1694-1699 ◽

Cited By ~ 6

Author(s):

Mei Shigematsu ◽

Ryosuke Nakagawa ◽

Shozo Tomonaga ◽

Masayuki Funaba ◽

Tohru Matsui

Keyword(s):

Citric Acid ◽

Control Diet ◽

Analysis Tool ◽

Mrna Levels ◽

Metabolomic Analysis ◽

Sprague Dawley ◽

Metabolic Disturbances ◽

Deficient Diet ◽

Mg Deficiency ◽

Metabolite Content

AbstractMg deficiency induces various metabolic disturbances including glucose metabolism in the liver. However, no comprehensive information is currently available on the metabolic pathways affected by Mg deficiency. The present study examined metabolite content in the liver of Mg-deficient rats using a metabolomic analysis. In this study, 4-week-old, male Sprague–Dawley rats were fed a control diet or a Mg-deficient diet for 8 weeks. The metabolomic analysis identified 105 metabolites in the liver, and significant differences were observed in the hepatic contents for thirty-three metabolites between the two groups. An analysis by MetaboAnalyst, a web-based metabolome data analysis tool, indicated that the Mg deficiency affected taurine/hypotaurine metabolism, methionine metabolism and glycine/serine/threonine metabolism; taurine, hypotaurine, glycine, serine and threonine contents were increased by Mg deficiency, whereas the amounts of 2-ketobutyric acid (a metabolite produced by the catabolism of cystathionine or threonine) and 5'-methylthioadenosine (a metabolite involved in spermidine synthesis) were decreased. The amount of glucose 6-phosphate, a hub metabolite of glycolysis/gluconeogenesis and the pentose phosphate pathway, was significantly decreased in Mg-deficient rats. Mg deficiency also decreased metabolite contents from the citric acid cycle, including citric acid, fumaric acid and malic acid. Aberrant metabolism may be related to the allosteric regulation of enzymes; the mRNA levels of enzymes were generally similar between the two groups. The present study suggests that the Mg deficiency-mediated modulation of hepatic metabolism is as yet uncharacterised.

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Retinoids synergize with insulin to induce hepatic Gck expression

Biochemical Journal ◽

10.1042/bj20082368 ◽

2009 ◽

Vol 419 (3) ◽

pp. 645-653 ◽

Cited By ~ 28

Author(s):

Guoxun Chen ◽

Yan Zhang ◽

Danhong Lu ◽

Nan-qian Li ◽

A. Catharine Ross

Keyword(s):

Specific Activity ◽

Retinoic Acid Receptor ◽

Regulatory Element ◽

Control Diet ◽

Underlying Mechanism ◽

Mrna Levels ◽

Sprague Dawley ◽

Deficient Diet ◽

Independent Manner ◽

Glucose Homoeostasis

Hepatic GK (glucokinase) plays a key role in maintaining glucose homoeostasis. Many stimuli regulate GK activity by controlling its gene transcription. We hypothesized that endogenous lipophilic molecules modulate hepatic Gck expression. Lipophilic molecules were extracted from rat livers, saponified and re-constituted as an LE (lipophilic extract). LE synergized with insulin to induce primary hepatocyte, but not β-cell, Gck expression in an SREBP-1c (sterol-regulatory-element-binding protein-1c)-independent manner. The dramatic induction of Gck mRNA resulted in a significant increase in GK activity. Subsequently, the active molecules were identified as retinol and retinal by MS after the purification of the active LE fractions. Retinoids synergized with insulin to induce Gck expression by the activation of both RAR [RA (retinoic acid) receptor] and RXR (retinoid X receptor). Inhibition of RAR activation completely abolished the effect of retinal. The hepatic GK specific activity and Gck mRNA levels of Zucker lean rats fed with a VAD [VA (vitamin A)-deficient] diet were significantly lower than those of rats fed with VAS (VA-sufficient) diet. Additionally, the hepatic Gck mRNA expression of Sprague–Dawley rats fed with a VAD diet was lower than that of rats fed with VA-marginal, -adequate or -supplemented diets. The reduced expression of Gck mRNA was increased after an intraperitoneal dose of RA in VAD rats. Furthermore, an intravenous injection of RA rapidly raised hepatic Gck expression in rats fed with a VAS control diet. Understanding the underlying mechanism that mediates the synergy may be helpful for developing a treatment strategy for patients with diabetes.

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Dietary Calcium Supplementation Suppresses Bone Formation in Magnesium-Deficient Rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.76.3.111 ◽

2006 ◽

Vol 76 (3) ◽

pp. 111-116 ◽

Cited By ~ 3

Author(s):

Hiroshi Matsuzaki ◽

Misao Miwa

Keyword(s):

Bone Formation ◽

Calcium Supplementation ◽

Control Diet ◽

Formation Rate ◽

Dietary Calcium ◽

Mineral Apposition Rate ◽

Control Group ◽

Deficient Diet ◽

Bone Formation Rate ◽

Male Wistar Rats

The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg - and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg - and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg - and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg - group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats.

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