Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of a short-term, high-dose intramuscular injection of d-alpha-tocopherol was studied in pigs given a challenge dose of lipopolysaccharide (LPS). Twenty-four pigs surgically fitted with jugular catheters were used in a 2 x 2 factorial design. Pigs received either 0 or 600 mg d-alpha-tocopherol by intramuscular injection for 3 d before receiving an intraperitoneal injection of saline containing either 0 or 5 microgram/kg body weight Escherichia coli LPS. Blood was collected from indwelling jugular catheters at 0, 1, 2, 4, 6, 8, 12 and 24 h after injection of LPS. Plasma alpha-tocopherol levels were 13-fold greater (P < 0.01) at time 0 in pigs pretreated with 600 mg d-alpha-tocopherol (9.9 +/- 1.3 mg/L) than in those not treated with d-alpha-tocopherol (0.74 +/- 0.09 mg/L). Injection of LPS increased (P < 0.05) plasma levels of interleukin-6 (IL-6) and cortisol at 2-h postinjection, regardless of vitamin E treatment. However, pigs that received alpha-tocopherol before the LPS challenge had substantially lower (P < 0.05) peak levels of IL-6 and cortisol than pigs not receiving alpha-tocopherol. These results suggest that supplementation with a surfeit level of vitamin E reduces the response of pigs to endotoxin.
 ...
PMID:Pretreatment of young pigs with vitamin E attenuates the elevation in plasma interleukin-6 and cortisol caused by a challenge dose of lipopolysaccharide. 977 32

Nitric oxide (NO), generated by endothelial (e) NO synthase (NOS) and neuronal (n) NOS, plays a ubiquitous role in the body in controlling the function of almost every, if not every, organ system. Bacterial and viral products, such as bacterial lipopolysaccharide (LPS), induce inducible (i) NOS synthesis that produces massive amounts of NO toxic to the invading viruses and bacteria, but also host cells by inactivation of enzymes leading to cell death. The actions of all forms of NOS are mediated not only by the free radical oxidant properties of this soluble gas, but also by its activation of guanylate cyclase (GC), leading to the production of cyclic guanosine monophosphate (cGMP) that mediates many of its physiological actions. In addition, NO activates cyclooxygenase and lipoxygenase, leading to the production of physiologically relevant quantities of prostaglandin E2 (PGE2) and leukotrienes. In the case of iNOS, the massive release of NO, PGE2, and leukotrienes produces toxic effects. Systemic injection of LPS causes induction of interleukin (IL)-1 beta mRNA followed by IL-beta synthesis that induces iNOS mRNA with a latency of two and four hours, respectively, in the anterior pituitary and pineal glands, meninges, and choroid plexus, regions outside the blood-brain barrier, and shortly thereafter, in hypothalamic regions, such as the temperature-regulating centers, paraventricular nucleus containing releasing and inhibiting hormone neurons, and the arcuate nucleus, a region containing these neurons and axons bound for the median eminence. We are currently determining if LPS similarly activates cytokine and iNOS production in the cardiovascular system and the gonads. Our hypothesis is that recurrent infections over the life span play a significant role in producing aging changes in all systems outside the blood-brain barrier via release of toxic quantities of NO. NO may be a major factor in the development of coronary heart disease (CHD). Considerable evidence has accrued indicating a role for infections in the induction of CHD and, indeed, patients treated with a tetracycline derivative had 10 times less complications of CHD than their controls. Stress, inflammation, and infection have all been shown to cause induction of iNOS in rats, and it is likely that this triad of events is very important in progression of coronary arteriosclerosis leading to coronary occlusion. Aging of the anterior pituitary and pineal with resultant decreased secretion of pituitary hormones and the pineal hormone, melatonin, respectively, may be caused by NO. The induction of iNOS in the temperature-regulating centers by infections may cause the decreased febrile response in the aged by loss of thermosensitive neurons. iNOS induction in the paraventricular nucleus may cause the decreased nocturnal secretion of growth hormone (GH) and prolactin that occurs with age, and its induction in the arcuate nucleus may destroy luteinizing hormone-releasing hormone (LHRH) neurons, thereby leading to decreased release of gonadotropins. Recurrent infections may play a role in aging of other parts of the brain, because there are increased numbers of astrocytes expressing IL-1 beta throughout the brain in aged patients. IL-1 and products of NO activity accumulate around the plaques of Alzheimer's, and may play a role in the progression of the disease. Early onset Parkinsonism following flu encephalitis during World War I was possibly due to induction of iNOS in cells adjacent to substantia nigra dopaminergic neurons leading to death of these cells, which, coupled with ordinary aging fall out, led to Parkinsonism. The central nervous system (CNS) pathology in AIDS patients bears striking resemblance to aging changes, and may also be largely caused by the action of iNOS. Antioxidants, such as melatonin, vitamin C, and vitamin E, probably play an important acute and chronic role in reducing or eliminating the oxidant damage produced by NO.
 ...
PMID:The nitric oxide hypothesis of aging. 995 25

Macrophage migration inhibitory factor (MIF), a putative cytokine involved in inflammatory and immune responses, was identified in rat peritoneal macrophages by Western blot analysis and its secretion into culture medium by enzyme-linked immunosorbent assay. To clarify the possibility of vitamin E as an immune modulator, we investigated the effect of vitamin E on MIF production in macrophages in response to calcium ionophore A23187 and lipopolysaccharide (LPS). Intraperitoneal injections of vitamin E (5 mg per rat) for 6 successive days resulted in a significant increase of alpha-tocopherol content in peritoneal macrophages. Alpha-tocopherol content of macrophages in vitamin E-treated rats was 478.3 +/- 90.7 ng/10(6) cells, whereas in control rats it was 1.5 +/- 0.5 ng/10(6) cells. For the control macrophages, total MIF content of the medium (2.5 x 10(6) cells/18 ml) without stimulation was 40.7 +/- 3.6 ng after 14 h culture, whereas stimulation with calcium ionophore A23187 (400 nM) and LPS (5.0 microg/ml) induced the elevation of MIF content to 65.9 +/- 7.5 ng and 74.3 +/- 10.4 ng, respectively (p < 0.05, n = 3). On the other hand, vitamin E-enriched macrophages without stimulation showed less MIF content (14.0 +/- 4.2 ng) than the control (p < 0.05, n = 3). Similarly, the increase of MIF of vitamin E-treated macrophages was significantly suppressed after stimulation with calcium ionophore A23187 or LPS, compared with the control macrophages (p < 0.01, n = 3). From analysis of intracellular MIF content by Western blot, we found no alteration of intracellular MIF content of vitamin E-macrophages, in contrast to the decreased content of control stimulated-macrophages, showing that vitamin E suppressed MIF secretion into the culture medium. Taken together, these results indicate that vitamin E may contribute to the regulation of inflammatory and immune responses through regulation of MIF secretion, possibly by modulating macrophage-membrane architecture.
 ...
PMID:Effect of vitamin E on production of macrophage migration inhibitory factor (MIF) by macrophages. 1060 75

Over the last decade, although investigations have suggested that vitamin E affects the immune response, not much is known about its affect on the alveolar macrophage functions. In the present study, we have investigated the effect of high vitamin E (DL-alpha-tocopheryl acetate, alpha-TA) supplementation for 10 d on the activation state of rat alveolar macrophages induced by lipopolysaccharide (LPS), interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha on the basis of their ability to produce reactive oxygen species (ROS), such as superoxide (O2-*) and H2O2. LPS treatment (1 and 10 microg/mL) caused 2.44 and 2.54-fold increases in O2-*, and 2.1 and 2.3-fold increases in H2O2, respectively, from alveolar macrophages (AMs) in the diet group fed 50 mg alpha-TA/kg. However, this enhancement was not observed for the AMs of the diet groups fed 250 or 1,250 mg alpha-TA/kg. Similar results were obtained on treating the AMs with proinflammatory cytokines IL-1beta or TNF-alpha. The observed suppression in ROS release in response to various stimulants may be due to the direct and/or indirect effect of high vitamin E (250 and 1,250 mg alpha-TA/kg diet) supplementation. It may therefore, be concluded that high alpha-TA supplementation in the diet modulates the activation of AMs in rats.
 ...
PMID:Vitamin E suppresses the induction of reactive oxygen species release by lipopolysaccharide, interleukin-1beta and tumor necrosis factor-alpha in rat alveolar macrophages. 1073 22

Compared with young mice, old mice infected with influenza virus have significantly higher pulmonary viral titres, although these can be reduced significantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines, especially interferon-gamma (IFN-gamma), play an important role in defending against influenza infection. However, there is an age-associated loss of Th1 cytokine production. Prostaglandin E2 (PGE2) production, which increases with age, can modulate the T helper cell function by suppressing Th1 cytokine production. To investigate the mechanism of vitamin E supplementation on reduction of influenza severity in old mice, we studied the cytokine production by splenocytes, and PGE2 production by macrophages (Mphi), in young and old C57BL mice fed semipurified diets containing 30 (control) or 500 parts per million (ppm) (supplemented) vitamin E for 8 weeks, and then infected with influenza A/PC/1/73 (H3N2). Old mice fed the control diet had significantly higher viral titres than young mice; old mice fed the vitamin E-supplemented diet had significantly lower pulmonary viral titres than those fed the control diet (P = 0.02 and 0.001 for overall age and diet effect, respectively). Following influenza infection, interleukin (IL)-2 and IFN-gamma production was significantly lower in old mice than in young mice. Vitamin E supplementation increased production of IL-2 and IFN-gamma in old mice; higher IFN-gamma production was associated with lower pulmonary viral titre. Old mice fed the control diet showed significantly higher lipopolysaccharide (LPS)-stimulated Mphi PGE2 production than old mice fed the vitamin E diet or young mice fed either diet. There was no significant age difference in IL-6, IL-1beta, or tumour necrosis factor-alpha (TNF-alpha) production by splenocytes. Young mice fed the vitamin E-supplemented diet had significantly lower IL-1beta (day 7) and TNF-alpha production (day 5) compared with those fed the control diet. Old mice fed the vitamin E-supplemented diet had significantly lower TNF-alpha production (day 2) than those fed the control diet. Our results indicate that the vitamin E-induced decrease in influenza viral titre is mediated through enhancement of Th1 cytokines, which may be the result of reduced PGE2 production caused by vitamin E.
 ...
PMID:Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus. 1092 76

Vitamin E is an efficient antioxidant and a modulator of the immune system. Although racial differences in both baseline vitamin E level and immunologic subsets are known, no reliable data exist for the Asian population. Furthermore, the extent of the effect of alpha-tocopherol in protecting lymphocyte cells against oxidative stress and its association with cell-mediated immunity have not been elucidated. This study was undertaken to investigate the immunologic and antioxidant effects of vitamin E in healthy ethnic Chinese men and women. Volunteers < 35 y old (n = 26) were supplemented with 233 mg/d dl-alpha-tocopherol for 28 d. The in vitro proliferative response to phytohemagglutinin (PHA) or lipopolysaccharide (LPS) of T-lymphocytes was determined in the study group before and after vitamin E supplementation. Cell-mediated immunity subsets and hydrogen peroxide production in T-lymphocytes were investigated by flow cytometry. The oxidant-antioxidant balance in plasma and urine was studied by spectrophotometric and gas chromatography-mass selective detection methods. The antioxidant properties of vitamin E were established (P: < 0.01) by the elevation of plasma vitamin E, together with depression in both plasma malondialdehyde and urinary DNA adduct 8-hydroxy-2'-deoxyguanosine after supplementation. Our data suggest a specific requirement for vitamin E in total-T and T-helper cell proliferation. We present the first evidence of the beneficial effects of supplemental vitamin E in healthy Chinese individuals on cell-mediated immunity and oxidative stress.
 ...
PMID:Vitamin E supplementation improves cell-mediated immunity and oxidative stress of Asian men and women. 1111 Aug 49

The use of aspirin in rheumatoid arthritis is limited since inhibition of the pro-inflammatory enzyme cyclooxygenase-2 occurs only at higher aspirin doses that are often associated with side effects such as gastric toxicity. Using a macrophage cell line (J774. 1A), the present study explores possible synergistic effects of aspirin and vitamin E on the expression and activity of cyclooxygenase-2. Lipopolysaccharide-induced prostaglandin E(2) formation was significantly reduced by aspirin (1-100 microM) or vitamin E (100-300 microM). When combined with vitamin E, aspirin-dependent inhibition of prostaglandin E(2) formation was increased from 59% to 95% of control. Likewise, lipopolysaccharide-induced cyclooxygenase-2 protein and mRNA expression were virtually abolished by the combined treatment of aspirin and vitamin E, whereas the two agents alone were only modestly effective. Vitamin C did not mimic the actions of vitamin E under these conditions, suggesting that redox-independent mechanisms underlie the action of vitamin E. In agreement with this, vitamin E and aspirin were without effect on lipopolysaccharide-induced translocation of the redox-sensitive transcription factor NF-kappa B. Our results show that co-administration of vitamin E renders cyclooxygenase-2 more sensitive to inhibition by aspirin by as yet unknown mechanisms. Thus, anti-inflammatory therapy might be successful with lower aspirin doses when combined with vitamin E, thereby possibly avoiding the side effects of the usually required high dose aspirin treatment.
 ...
PMID:Synergistic inhibition of cyclooxygenase-2 expression by vitamin E and aspirin. 1112 21

The major goal of this study was to examine the ability of several antioxidants namely, vitamin E, beta-carotene and N-acetylcysteine, to protect the brain from oxidative stress induced by lipopolysaccharide (LPS, endotoxin). LPS, a component of the bacterial wall of gram-negative bacteria, has been recognized as one of the most potent bacterial products in the induction of host inflammatory responses and tissue injury and was used in this study to mimic infections. LPS injection resulted in a significant increase in the stress indices, plasma corticosterone and glucose concentration, a significant alteration of the brain oxidative status observed as elevation of the level of malondialdehyde (MDA, index of lipid peroxidation) and reduction of reduced glutathione (GSH), and a disturbance in the brain energy metabolism presented as a reduction in the ATP/ADP ratio and an increase in the mitochondrial/cytosolic hexokinase ratio. However, the activities of brain superoxide dismutase and Na+, K+-ATPase and contents of cholesterol and phospholipids were not altered. Administration of the aforementioned antioxidants prior to LPS injection ameliorated the oxidative stress by reducing levels of MDA, restoring GSH content and normalizing the mitochondrial/cytosolic hexokinase ratio in the brain in addition to lowering levels of plasma corticosterone and glucose. In conclusion, this study showed the increased free radical generation during infections and LPS-induced stress. It also suggests that brain oxidative status and energy is disturbed.
 ...
PMID:Protective effect of vitamin E, beta-carotene and N-acetylcysteine from the brain oxidative stress induced in rats by lipopolysaccharide. 1133 Dec 2

Vitamin E (dl-alpha-tocopheryl acetate) was evaluated for its effects on performance, lymphocyte proliferation, and antioxidation in layers during heat stress. In Trial 1, 25, 45, or 65 IU of vitamin E/kg were fed to four replicated pens (five hens/cage) of DeKalb Delta or Hy-Line W-36 per treatment starting at 20 wk of age. At 34 wk of age, hens were heat-stressed at diurnal temperature ranging from 21 C to 35 C for 3 wk. The performances of hens not exposed to heat stress were not influenced by supplemental vitamin E. Supplemental vitamin E did not affect egg production; however, egg mass was greater (P < 0.05) with supplementation of 65 IU of vitamin E/ kg during heat stress. Egg yolk was significantly increased (P < 0.04) when hens were fed 45 and 65 lU/kg compared with the control vitamin E level (25 lU/kg). Haugh units were higher (P < 0.01) for hens fed 65 IU of vitamin E/kg compared to 25 and 45 lU/kg. Lymphocyte proliferative responses to concanavalin A (Con A) and Salmonella typhimurium lipopolysaccharide (LPS) were greater (P < 0.0001) in hens fed 45 and 65 IU of vitamin E/kg during heat stress. Strain had no effect on any of the parameters measured. In Trial 2, a 2 x 2 factorial was designed to test effects of vitamin C in drinking water (0 and 1,000 ppm) and dietary vitamin E (25 and 65 IU/kg). Eight replications per treatment with four hens per replication cage were heat-stressed at constant temperature of 35 C for 3 wk. Egg production and egg mass were higher when hens were fed 65 IU of vitamin E/kg than when hens were fed 25 lU/kg (81.5 vs. 75.9%, P < 0.03 and 48.2 vs. 44.6 g, P < 0.03, respectively). Yolk solids weight for the 65 IU vitamin E/kg group was higher (P < 0.01) compared to the 25 IU/kg group. ConA and LPS mitogenic responses were greater in hens fed 65 IU of vitamin E (P < 0.001 or P < 0.003, respectively) or 1,000 ppm of vitamin C (P < 0.001 or P < 0.002, respectively). The combination of 65 IU vitamin E/kg and 1,000 ppm vitamin C showed the highest ConA and LPS mitogenic responses among the treatments. No interaction effects of the two vitamins on production measurements or lymphocyte proliferative responses were observed. TBA values in egg yolk and plasma of hens fed 65 IU of vitamin E/kg were lower (P < 0.0001) than those of hens that received 25 IU of vitamin E/kg. These results suggest that vitamin E supplementation at 65 IU/kg diet may enhance production, induction of in vitro lymphocyte proliferation by ConA and LPS, and antioxidant properties of egg yolks and plasma of White Leghorn hens during heat stress and that supplementation of 1,000 ppm vitamin C may further enhance in vitro lymphocyte proliferative responses of hens during heat stress.
 ...
PMID:Effects of vitamin E and C supplementation on performance, in vitro lymphocyte proliferation, and antioxidant status of laying hens during heat stress. 1149 72

Our aim was to study the antioxidant and immunomodulatory effect of silibinin and vitamin E on the early postoperative course in rats that had undergone a partial hepatectomy (PHX). Male Wistar rats that were treated with silibinin (50 mg/b.w.kg i.p.) and/or vitamin E (500 mg/b.w.kg p.o.) were randomised to undergo 70% PHX. At 72 h after operation, Concanavalin A (Con-A) induced lymphocyte proliferation, and lipopolysaccharide (LPS) induced interleukin-1 (IL-1) mitogenicity and tumour necrosis factor-alpha (TNF-alpha) cytotoxicity were measured in the spleen. In addition, total free radical scavenger capacity of the liver was analysed. In PHX animals, Con-A induced lymphocyte proliferation was significantly decreased, and both LPS induced IL-1 and TNF-alpha activity were significantly increased as compared to Sham treated animals. Treatment with silibinin and vitamin E synergistically restored both lymphocyte proliferation (P<0.01) and cytokine activity (P<0.001) in PHX animals. In addition, silibinin and vitamin E synergistically (P<0.001) restored total hepatic free radical scavenger capacity as well as serum levels of AST and gammaGT, that were all markedly decreased in PHX animals. Our results suggest that preoperative treatment with silibinin and/or vitamin E modulates the cellular immunoresponse and restores impaired liver function following PHX, presumably through their antioxidant capacity. This may explain their beneficial effects on the postoperative course of liver repair.
 ...
PMID:Effect of silibinin and vitamin E on restoration of cellular immune response after partial hepatectomy. 1153 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>