Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E

1994 ◽  
Vol 267 (3) ◽  
pp. G476-G484 ◽  
Author(s):  
T. Yao ◽  
S. Degli Esposti ◽  
L. Huang ◽  
R. Arnon ◽  
A. Spangenberger ◽  
...  

We tested a variety of antioxidants as possible therapeutic agents in an acute CCl4 mouse model of hepatotoxicity. Liver damage, gauged by the amount of serum aminotransferase released into the blood, morphological changes, lethal dose response, and presence of thiobarbituric acid-reactive substances (TBARS), were significantly inhibited in a dose-dependent manner by liposomes containing vitamin E (LVE) or by Rocavit E, a water-soluble emulsion of alpha-tocopherol. Serum aminotransferase levels in LVE- or Rocavit E-treated animals were always > 10-fold lower than levels in corresponding CCl4 controls. Other liposome-associated antioxidants, butylated hydroxytoluene, vitamin E succinate, catalase, desferoxamine, superoxide dismutase, and ascorbic acid 6-palmitate, were also able to elicit a decrease in damage; however, they were substantially less effective. Intravenous therapy with LVE decreased mortality by nearly 90% when a lethal dose of CCl4 was given. When the biodistribution of the liposomes was examined, it was determined that the vast majority were localized in the Kupffer cell population. This approach of delivering nontoxic therapeutic agents selectively to the liver offers a variety of clinical applications in humans.

2010 ◽  
Vol 55 (No. 9) ◽  
pp. 388-397 ◽  
Author(s):  
M. Skřivan ◽  
I. Bubancová ◽  
M. Marounek ◽  
G. Dlouhá

The effect of supplementing dietary selenium (Se) and vitamin E was investigated in 330 24-week-old laying hens. The hens were fed a basal diet containing Se and α-tocopherol at 0.11 and 26 mg/kg, respectively, or a diet supplemented with Se at 0.3 mg/kg and vitamin E between 0 and 625 mg/kg. Se was supplied as Se-methionine or sodium selenite. The eggs were collected for analysis during the third, seventh and eleventh weeks of the experiment. Supplementation of either form of Se significantly increased the Se concentration in egg yolks and whites, with a more pronounced effect caused by Se-methionine. The egg yolk α-tocopherol concentration paralleled the dietary α-tocopherol concentration. At a high dietary α-tocopherol concentration (632 mg/kg), the retinol content in egg yolks from hens fed Se-methionine increased significantly. Supplementation of Se-methionine significantly increased the α-tocopherol content in the eggs in the third and seventh weeks of the experiment. A moderate decrease in yolk cholesterol was observed in hens fed Se-methionine and α-tocopherol at 119 mg/kg. The concentration of products from lipid peroxidation (thiobarbituric acid-reactive substances, TBARS) in egg yolks increased marginally during the refrigerated storage of the eggs for 2 weeks. The effect of dietary vitamin E on TBARS formation was generally small, although a more significant effect was observed at the highest dose tested.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kathryn Hall ◽  
Stephanie Weinstein ◽  
Julie Buring ◽  
Kenneth Mukamal ◽  
M Vinayaga Moorthy ◽  
...  

Abstract Objectives Despite promising observational data and compelling mechanisms of action, vitamin E has failed to demonstrate evidence of benefit in randomized clinical trials (RCTs). In two large long-term placebo-controlled RCTs, we reported that vitamin E effects on total cancer were modified by genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. Here we investigate COMT effects on colorectal cancer (CRC) in the two RCTs and a CRC cell line. Methods We analyzed COMT rs4680 association with rates of CRC in the Women's Health Study (WHS), N = 23,294 and a case/control (N = 2396/2235) subset of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC). Cell survival and apoptosis were examined in-vitro in HCT116 cells treated with increasing doses of vitamin E when COMT gene expression was inhibited by silencing RNA (siRNA). Results Rates of CRC were higher with randomized vitamin E compared to placebo among COMT high-activity val/val homozygotes in ATBC (HR, [CI] = 3.00, [1.48–6.09]), but not WHS (HR, [CI] = 0.99, [0.63–1.57]). Among low-activity met/met homozygotes randomized to vitamin E compared to placebo, rates of CRC were borderline lower in WHS (HR, [CI] = 0.66, [0.44–1.01]), but not in ATBC (HR, [CI] = 0.93, [0.63–1.62]). In cell culture, vitamin E at 3 µg/ml and 10 µg/mL had no effect on cell viability or apoptosis. However, silencing COMT resulted in a modest apoptotic effect that vitamin E enhanced in a dose-dependent manner. Human apoptosis arrays indicated that in the absence of COMT expression, vitamin E induced protein expression related to the intrinsic apoptotic pathway through p53 activation, dysregulation of Bcl-2 family protein expression and down-regulation of IAP family protein expression. Conclusions Differential COMT effects on vitamin E and CRC were similar to those previously reported for all invasive cancers, but were only significant for val/val homozygotes. Further, inhibiting COMT in the presence of vitamin E in a CRC in-vitro model, recapitulated the RCT observation that among individuals homozygous for the low-activity allele (met/met) vitamin E tended to reduce invasive cancer and here CRC. Funding Sources National Institutes of Health: NCI and NHLBI.


2021 ◽  
Vol 9 (2) ◽  
pp. 206-213
Author(s):  
Kamal Alhammad ◽  
◽  
Nazlin Howell ◽  
Nazrul Haq ◽  
◽  
...  

Nowadays food industries were concentrating on substituting the use of synthetic natural “green” antioxidants. Therefore, the present study focused on lipid oxidations in dried salmon (Salmo salar) with and without natural antioxidants (garlic powder, cinnamon) during different storage conditions, and a comparison was made with a synthetic antioxidant Butylated hydroxytoluene (BHT). Minced salmon fillet mass was divided into four equal parts and each part was treated with natural antioxidant under study except the control. Each of these four parts was dried in two different ways, half portion oven-dried and the other half portion freeze-dried. After 24 weeks, these samples were tested for peroxide value (PV), Thiobarbituric acid reactive substances (TBARS), total carbonyl content/water-soluble protein. According to the peroxide value (PV) results, it was noticed that the BHT was found to be the most effective antioxidant, followed by garlic and cinnamon for oven-dried salmon. Cinnamon was found to be more efficient than garlic in minimizing PV formation in freeze-dried salmon. In general, the initial study showed that freeze-drying was more efficient than oven drying. On the other hand, total carbonyl content for oven-dried salmon treated with cinnamon, garlic, and BHT, was found to be similar to the untreated salmon. Freeze-dried antioxidant treated salmon was generally found to possess more carbonyl content over time compared to the oven dried treated salmon.


2021 ◽  
Author(s):  
Priyanka Joshi ◽  
Sean Chia ◽  
Xiaoting Yang ◽  
Michele Perni ◽  
Johnny Habchi ◽  
...  

Alzheimer's disease is characterized by the presence in the brain of amyloid plaques formed by the aberrant deposition of the amyloid-beta; peptide (Abeta). Since many vitamins are dysregulated in this disease, we explored whether these molecules participate in protein homeostasis by modulating Abeta; aggregation. By screening 18 fat-soluble and water-soluble vitamins, we found that retinoic acid and alpha-tocopherol, two metabolites of vitamin A and vitamin E, respectively, affect Abeta; aggregation both in vitro and in a C. elegans model of Alzheimer's disease. We also show that effects of these two vitamin metabolites in combination can cancel each other out, suggesting that the complex composition of the cellular environment could have a protective role against protein aggregation through the simultaneous presence of aggregation promoters and inhibitors. Taken together, these results indicate that vitamins and their metabolites may be added to the list of components of the quality control system that regulate protein aggregation.


Author(s):  
A. Aigbiremolen ◽  
M. A. Omoirri ◽  
O. A. Udi ◽  
S. E. Iloh ◽  
M. Ogbonnaya

Background: Though prolonged use of glucocorticoids has been reported to promote adverse effects, traditionally, high-dose glucocorticoids have been implicated in immune-suppression following organ transplant with Cortisone being a well-known artificial glucocorticoid. Objectives: This study investigated the histo-architectural and functional changes in pancreatic beta cells due to Cortisone administration. Materials and Methods: Forty two (42) Wistar rats (140 – 200 kg) were assigned into seven groups of six (6) rats each with group A acting as a control. While groups B and C were respectively treated with 0.1 mg/kg and 0.3 mg/kg of Cortisone, groups D and E received 0.1 mg/kg and 0.3 mg/kg of Cortisone respectively plus 33 mg/kg of Ketoconazole; whereas, groups F and G were respectively given 0.1 mg/kg and 0.3 mg/kg of Cortisone alongside 150 mg/kg of Vitamin E each for twenty-eight (28) days. After 28 days of administration, rats were euthanized and blood samples collected for insulin assay. Pancreatic tissues were also harvested and observed for histo-morphological changes. Results: Analysis of variance (ANOVA) found Cortisone to have significantly (p < .05) increased glucose level in a dose dependent manner. This was however attenuated following co-administration of Ketoconazole and Vitamin E as Ketoconazole showed more potency in this ameliorating effect. Also, Cortisone was observed to significantly decrease (in dose dependent fashion), pancreatic β-cell functions, with attenuating effect seen following co-administration of Ketoconazole. Conclusion: It is recommended that caution is applied with the intake of glucocorticoids, especially in polypharmacy while treating certain ailments.


2006 ◽  
Vol 290 (6) ◽  
pp. C1495-C1502 ◽  
Author(s):  
Hideyuki Yamawaki ◽  
Naoharu Iwai

Nanoscale materials are presently under development for diagnostic (nanomedicine) and electronic purposes. In contrast to the potential benefits of nanotechnology, the effects of nanomaterials on human health are poorly understood. Nanomaterials are known to translocate into the circulation and could thus directly affect vascular endothelial cells (ECs), causing vascular injury that might be responsible for the development of atherosclerosis. To explore the direct effects of nanomaterials on endothelial toxicity, human umbilical vein ECs were treated with 1–100 μg/ml hydroxyl fullerene [C60(OH)24; mean diameter, 7.1 ± 2.4 nm] for 24 h. C60(OH)24 induced cytotoxic morphological changes such as cytosolic vacuole formation and decreased cell density in a dose-dependent manner. Lactate dehydrogenase assay revealed that a maximal dose of C60(OH)24 (100 μg/ml) induced cytotoxic injury. Proliferation assay also showed that a maximal dose of C60(OH)24 inhibited EC growth. C60(OH)24 did not seem to induce apoptosis but caused the accumulation of polyubiquitinated proteins and facilitated autophagic cell death. Formation of autophagosomes was confirmed on the basis of Western blot analysis using a specific marker, light chain 3 antibody, and electron microscopy. Chronic treatment with low-dose C60(OH)24 (10 μg/ml for 8 days) inhibited cell attachment and delayed EC growth. In the present study, we have examined, for the first time, the toxicity of water-soluble fullerenes to ECs. Although fullerenes changed morphology in a dose-dependent manner, only maximal doses of fullerenes caused cytotoxic injury and/or death and inhibited cell growth. EC death seemed to be caused by activation of ubiquitin-autophagy cell death pathways. Although exposure to nanomaterials appears to represent a risk for cardiovascular disorders, further in vivo validations are necessary.


2018 ◽  
Vol 38 (4) ◽  
pp. 679-684
Author(s):  
Aline A. Morgado ◽  
Giovanna R. Nunes ◽  
Beatriz R. Villas Bôas ◽  
Paola B.J. Carvalho ◽  
Paulo H.M. Rodrigues ◽  
...  

ABSTRACT: This study evaluated the effects of intramuscular alpha-tocopherol (vitamin E) supplementation on meat quality characteristics of Santa Inês and Dorper crossbreed lambs. All animals were feed with a high concentrated diet in feedlot. Eight days before slaughter, the animals were distributed into four blocks according to weight gain. At the seventh and fourth days before slaughter, they were intramuscularly treated with 0, 10 or 20 IU of DL-alpha-tocopherol per kg of metabolic body weight. At slaughter they had 138 days of age and 43.6 kg of live weight, in average. Carcasses were stored for 24 hours under refrigeration at 2°C. Longissimus thoracis muscle pH (pH24h) and color (lightness, yellowness and redness) were analyzed and its samples were collected for evaluation of shear force (SF), cooking loss (WLC), fatty acid composition (FA) and thiobarbituric acid reactive substances after one (TBARS1m) and after five months (TBARS5m) of freezing. Linearity deviation effect was observed for lightness (L*; P=0.0042) and yellowness (b*; P=0.0082). Intramuscular administration of 10 or 20 IU of alpha-tocopherol/kg of metabolic weight did not influence the conservation of fatty acid in the carcasses, but benefit L* and b* values.


1994 ◽  
Vol 267 (5) ◽  
pp. C1366-C1370 ◽  
Author(s):  
I. T. Mak ◽  
R. Stafford ◽  
W. B. Weglicki

Mg deficiency results in loss of red blood cell glutathione and was thought to be due to decreased Mg-dependent synthesis. The effects of vitamin E, D-propranolol, and chloroquine on red blood cell glutathione levels in Mg-deficient rats were examined. Feeding the rats a Mg-deficient diet for 3 wk resulted in an approximately 80% decrease in serum Mg and a 55% loss of red blood cell glutathione; concomitantly, plasma thiobarbituric acid reactive (TBAR) materials rose 240%. All three drug treatments had no effect on the plasma Mg levels but significantly inhibited the rise in TBAR content and attenuated (60-80% effective) the loss of glutathione. Red blood cell ghost membranes from the Mg-deficient rats also exhibited 2.3-fold higher TBAR content, which was attenuated by vitamin E treatment. With isolated red blood cells from Mg-sufficient rats, loss of glutathione could be induced by a chemical oxyradical system. Direct protective effects were afforded by alpha-tocopherol and D-propranolol but not by chloroquine. The data suggest that 1) the loss of glutathione during Mg deficiency was due to increased oxidative degradation, 2) both vitamin E and D-propranolol protected by a membrane antiperoxidative action, and 3) chloroquine probably protected by diminishing prooxidant activity secondary to its inhibition of cytokine induction during Mg deficiency.


2006 ◽  
Vol 53 (3) ◽  
pp. 547-552 ◽  
Author(s):  
Adriana Sampayo-Reyes ◽  
Robert A Zakharyan

Human glutathione S-transferase omega 1-1 (hGSTO1-1) is a newly identified member of the glutathione S-transferase (GST) family of genes, which also contains alpha, mu, pi, sigma, theta, and zeta members. hGSTO1-1 catalyzes the reduction of arsenate, monomethylarsenate (MMA(V)), and dimethylarsenate (DMA(V)) and exhibits thioltransferase and dehydroascorbate reductase activities. Recent evidence has show that cytokine release inhibitory drugs, which specifically inhibit interleukin-1b (IL-1b), directly target hGSTO1-1. We found that (+)-alpha-tocopherol phosphate and (+)-alpha-tocopherol succinate inhibit hGSTO1-1 in a concentration-dependent manner with IC50 values of 2 microM and 4 microM, respectively. A Lineweaver-Burk plot demonstrated the uncompetitive nature of this inhibition. The molecular mechanism behind the inhibition of hGSTO1-1 by alpha-tocopherol esters (vitamin E) is important for understanding neurodegenerative diseases, which are also influenced by vitamin E.


2020 ◽  
Vol 56 (65) ◽  
pp. 9332-9335
Author(s):  
Sandra Estalayo-Adrián ◽  
Salvador Blasco ◽  
Sandra A. Bright ◽  
Gavin J. McManus ◽  
Guillermo Orellana ◽  
...  

Two new water-soluble amphiphilic Ru(ii) polypyridyl complexes were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and phototoxicity against HeLa cervical cancer cells.


Sign in / Sign up

Export Citation Format

Share Document