Gamma-tocotrienol profoundly alters sphingolipids in cancer cells by inhibition of dihydroceramide desaturase and possibly activation of sphingolipid hydrolysis during prolonged treatment.

Jang Y, Rao X, Jiang Q

J Nutr Biochem. 2017 Apr 12;46:49-56. doi: 10.1016/j.jnutbio.2017.04.003. [Epub ahead of print]

Abstract

Vitamin E gamma-tocotrienol (γTE) is known to have anticancer effects, but mechanisms underlying these actions are not clear. Here using liquid chromatography tandem mass spectrometry, we show that γTE induced marked changes of sphingolipids including rapid elevation of dihydrosphingosine and dihydroceramides (dhCers) in various types of cancer cells. The elevation of dihydrosphingolipids coincided with increased cellular stress, as indicated by JNK phosphorylation, and was prior to any sign of induction of apoptosis. Chemically blocking de novo synthesis of sphingolipids partially counteracted γTE-induced apoptosis and autophagy. Experiments using 13C3, 15N-labeled l-serine together with enzyme assays indicate that γTE inhibited cellular dihydroceramide desaturase (DEGS) activity without affecting its protein expression or de novo synthesis of sphingolipids. Unlike the effect on dhCers, γTE decreased ceramides (Cers) after 8-h treatment but increased C18:0-Cer and C16:0-Cer after 16 and 24 h, respectively. The increase of Cers coincides with γTE-induced apoptosis and autophagy. Since γTE inhibits DEGS and decreases de novo Cer synthesis, elevation of Cers during prolonged γTE treatment is likely caused by sphingomeylinase-mediated hydrolysis of sphingomyelin. This idea is supported by the observation that an acid sphingomeylinase inhibitor partially reversed γTE-induced cell death. Our study demonstrates that γTE altered sphingolipid metabolism by inhibiting DEGS activity and possibly by activating SM hydrolysis during prolonged treatment in cancer cells.

Read More

Development and Evaluation of Resveratrol, Vitamin E, and Epigallocatechin Gallate Loaded Lipid Nanoparticles for Skin Care Applications.

Chen J, Wei N, Lopez-Garcia M, Ambrose D, Lee J, Annelin C, Peterson T.

Eur J Pharm Biopharm. 2017 Apr 11. pii: S0939-6411(17)30452-6. doi: 10.1016/j.ejpb.2017.04.008. [Epub ahead of print]

Abstract

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied as potential carriers for both dermal and transdermal drug delivery. SLN contain lipid droplets that are fully crystallized and have a highly-ordered crystalline structure. NLC are modified SLN in which the lipid phase contains both solid and liquid lipids at room temperature. SLN and NLC are thought to combine the advantages of polymeric particles, liposomes and emulsions. Therefore they provide high encapsulation percentages, better protection for incorporated actives and allow for control of desired release profile. In this work, Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent antioxidants known to provide protection to the skin, were formulated into lipid nanoparticles. Several different formulations were successfully developed and demonstrated high uniformity and stability. Both resveratrol and VE lipid nanoparticles provided effective protection of actives against UV induced degradation. However, lipid nanoparticles did not show protection from UV degradation for EGCG in this work. An active release study exhibited a sustained release of resveratrol over 70% after 24hrs. Skin penetration studies showed that lipid nanoparticles directionally improved the penetration of resveratrol through the stratum corneum. Our findings suggest that lipid nanoparticles are promising viable carriers for the delivery of resveratrol and VE to provide longlasting antioxidant benefits to the skin.

Read More

Combination of vitamin E and vitamin C alleviates renal function in hyperoxaluric rats via antioxidant activity.

Jaturakan O, Dissayabutra T, Chaiyabutr N, Kijtawornrat A, Tosukhowong P, Rungsipipat A, Nhujak T, Buranakarl C.

J Vet Med Sci. 2017 Apr 8. doi: 10.1292/jvms.17-0083. [Epub ahead of print]

Abstract

Hyperoxaluria and oxidative stress are risk factors in calcium oxalate (CaOx) stone formation. Supplement with antioxidant could be effective in prevention of recurrent stone formation. The present study aims to evaluate the protective effects of vitamin E and vitamin C in hyperoxaluric rat. The experiment was performed in rats for 21 days. Rats were divided into 5 groups as follows: control (group 1, n=8), hyperoxaluric rats (group 2, n=8), hyperoxaluric rats with vitamin E supplement (group 3, n=7), hyperoxaluric rats with vitamin C supplement (group 4, n=7) and hyperoxaluric rats with vitamin E and C supplement (group 5, n=7). Hyperoxaluria was induced by feeding hydroxyl L-proline (HLP) 2% w/v dissolved in drinking water. Intraperitoneal 200 mg/kg of vitamin E was given in groups 3 and 5 on days 1, 6, 11 and 16, while 500 mg of vitamin C was injected intravenously in groups 4 and 5 on days 1 and 11. Renal functions and oxidative status were measured. The urinary oxalate excretion was increased in HLP supplement rats, while glomerular filtration rate, proximal water and sodium reabsorption were significantly lower in group 2 compared with a control (P<0.05). Giving antioxidants significantly lower urinary calcium oxalate crystals (P<0.05). Hyperoxaluric rats had higher plasma malondialdehyde (pMDA) and lower urinary total antioxidant status (uTAS), which were alleviated by vitamin E and/or vitamin C supplement. In conclusion, giving combination of vitamin E and vitamin C exerts a protective role against HLP-induced oxalate nephropathy.

Read More

Combined effects of vitamin E and omega-3 fatty acids on protecting ambient PM2.5-induced cardiovascular injury in rats.

Du X, Jiang S, Bo L, Liu J, Zeng X, Xie Y, He Q, Ye X, Song W, Zhao J.

Chemosphere. 2017 Apr;173:14-21. doi: 10.1016/j.chemosphere.2017.01.042. Epub 2017 Jan 8.

Abstract

This study aims to observe whether the combined treatment with vitamin E (vit E) and omega-3 polyunsaturated fatty acids (Ω-3 FA) could prevent the fine particulate matter (PM2.5)-induced cardiovascular injury through alleviating inflammation and oxidative stress. At the same time, the appropriate combination dosage of vit E and Ω-3 FA was explored to find an optimized protective dose to protect the injury induced by PM2.5. The SD rats were pretreated with different concentration of vit E and Ω-3 FA separately or jointly. Then the rats were exposed to ambient PM2.5 by intratracheal instillation for three times. The expression of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) in serum and supernatant of cardiac tissue were detected by ELISA kits. The levels of malondialdehyde (MDA), superoxide Dismutase (SOD) and glutathione-peroxidase (GSH-Px) in myocardium and the level of MDA in serum were measured. Meanwhile, the cardiac injury was evaluated by histopathological examination. Compared with the severe injury of rats in PM2.5 exposure group, the rats in vit E or Ω-3 FA-pretreated groups had a slighter injury in heart. Meanwhile, pretreatment with vit E or Ω-3 FA induced a significantly alleviation of the inflammatory cytokines (TNF-α, IL-1β, IL-6) and the elevation of the anti-oxidative activity especially in the rats pretreated with combined vit E and Ω-3 FA. In addition, the combined protecting effects of vit E and Ω-3 FA showed a dose-dependent manner. Supplementation with vit E and Ω-3 FA could protect the PM2.5-induced injury, and the combination of vit E and Ω-3 FA might produce more effective effects than the separate nutrient did.

Read More

The effects of co-administration of pregabalin and vitamin E on neuropathic pain induced by partial sciatic nerve ligation in male rats.

Meymandi MS, Sepehri G, Abdolsamadi M, Shaabani M, Heravi G, Yazdanpanah O, Aghtaei MM.

Inflammopharmacology. 2017 Apr;25(2):237-246. doi: 10.1007/s10787-017-0325-4. Epub 2017 Feb 23.

Abstract

This study was performed to evaluate the effect of pregabalin co-administration with vitamin E in Partial Sciatic Nerve Ligation (PSNL)-induced neuropathic pain in rats. Male Wistar rats were randomly allocated as control, sham, and PSNL groups (n = 8). PSNL was induced by tight ligation of the sciatic nerve with a copper wire. On day 14th, the PSNL and sham operated rats received either pregabalin (1, 3, and 30 mg/kg), vitamin E (100 and 200 mg/kg), or their combination intraperitoneally. An antinociceptive effect was evaluated as latency times and Maximum possible Effect Percent (%MPE) using tail-flick test. Locomotor activity was evaluated by open-field test before PSNL surgery and then twice at the 14th days (before and after drug injection). Ligated nerves were removed on the 28th days after surgery for histological examinations. The time course of latency times and %MPE showed significant decrease in PSNL but not in sham and control groups. Pregabalin (3 and 30 mg/kg) and vitamin E (100 and 200 mg/kg) caused significant increases in latency time in PSNL (but not sham) group compared to control group. Vitamin E 200 mg/kg increased significantly %MPE in PSNL group compared to sham group. In addition, the %MPE following combination treatment of pregabalin (30 mg/kg) and vitamin E (100 mg/kg) was significantly higher than both vitamin E and control group. Also combination of pregabalin with 100 mg/kg of vitamin E reversed Wallerian degeneration of sciatic nerve and the inflammatory responses to almost similar to sham group. Pregabalin and vitamin E did not affect locomotor activity. Our results showed antinociceptive effects of both vitamin E and pregabalin alone or in combination in PSNL rats and also neuroprotective properties without affecting locomotor activity.

Read More

CYP4F2 repression and a modified alpha-tocopherol (vitamin E) metabolism are two independent consequences of ethanol toxicity in human hepatocytes.

Russo A, Bartolini D, Torquato P, Giusepponi D, Barola C, Galarini R, Birringer M, Lorkowski S, Galli F.

Toxicol In Vitro. 2017 Apr;40:124-133. doi: 10.1016/j.tiv.2016.12.014. Epub 2017 Jan 3.

Abstract

The expression of CYP4F2, a form of cytochrome P-450 with proposed role in α-tocopherol and long-chain fatty acid metabolism, was explored in HepG2 and HepaRG human hepatocytes during ethanol toxicity. Cytotoxicity, ROS production, and JNK and ERK1/2 kinase signaling increased in a dose and time-dependent manner during ethanol treatments; CYP4F2 gene expression decreased, while other CYP4F forms, namely 4F11 and 12, increased along with 3A4 and 2E1 isoforms. α-Tocopherol antagonized the cytotoxicity and CYP4F2 gene repression effect of ethanol in HepG2 cells. Ethanol stimulated the tocopherol-ω-hydroxylase activity and the other steps of vitamin E metabolism, which points to a minor role of CYP4F2 in this metabolism of human hepatocytes. PPAR-γ and SREBP-1c followed the same expression pattern of CYP4F2 in response to ethanol and α-tocopherol treatments. Moreover, the pharmacological inhibition of PPAR-γ synergized with ethanol in decreasing CYP4F2 protein expression, which suggests a role of this nuclear receptor in CYP4F2 transcriptional regulation. In conclusion, ethanol toxicity modifies the CYP expression pattern of human hepatic cells impairing CYP4F2 transcription and protein expression. These changes were associated with a lowered expression of the fatty acid biosynthesis regulators PPAR-γ and SREBP-1c, and with an increased enzymatic catabolism of vitamin E. CYP4F2 gene repression and a sustained vitamin E metabolism appear to be independent effects of ethanol toxicity in human hepatocytes.

Read More

Using vitamin E to prevent the impairment in behavioral test, cell loss and dendrite changes in medial prefrontal cortex induced by tartrazine in rats.

Rafati A, Nourzei N, Karbalay-Doust S, Noorafshan A.

Acta Histochem. 2017 Mar;119(2):172-180. doi: 10.1016/j.acthis.2017.01.004. Epub 2017 Jan 23.

Abstract

Tartrazine is a food color that may adversely affect the nervous system. Vitamin E is a neuro-protective agent. This study aimed to evaluate the effects of tartrazine and vitamin E on the performance of rats in memory and learning tests as well as the structure of medial Prefrontal Cortex (mPFC). The rats were first divided into seven groups which received the followings for a period of seven weeks: distilled water, corn oil, vitamin E (100mg/kg/day), a low dose (50mg/kg/day) and a high dose (50mg/kg/day) of tartrazine with and without vitamin E. Behavioral tests were conducted and the brain was extracted for stereological methods The high dose of tartrazine decreased the exploration time of novel objects (P<0.01). The low and high doses of tartrazine led into an increase in working and reference memory errors in acquisition and retention phases (eight-arm radial maze) compared to distilled water group (P<0.01). Additionally, the high dose of tartrazine induced a reduction in the volume of mPFC (∼13%) and its subdivision. Not only that, but the number of neurons and glial cells (∼14%) as well as the mushroom and thin spines per dendrite length declined. The length of dendrites per neuron also reduced in comparison to the distilled water group (P<0.01). Nonetheless, concomitant treatment of the rats with vitamin E plus tartrazine prevented the above-mentioned changes. An acceptable daily dose of tartrazine could induce impairment in spatial memory and dendrite structure. Moreover, a high dose of tartrazine may defect the visual memory, mPFC structure, the spatial memory and also cause dendrite changes. Vitamin E could prevent the behavioral and structural changes.

Read More

Association of dietary vitamin E intake with risk of lung cancer: a dose-response meta-analysis.

Zhu YJ, Bo YC, Liu XX, Qiu CG.

Asia Pac J Clin Nutr. 2017 Mar;26(2):271-277. doi: 10.6133/apjcn.032016.04.

Abstract

Several epidemiological studies investigating the association between dietary vitamin E intake and the risk of lung cancer have demonstrated inconsistent results. Hence, a meta-analysis was conducted to summarise evidence of the association of dietary vitamin E intake with the risk of lung cancer. In this meta-analysis, a systematic literature search of PubMed and Web of Science was conducted to identify relevant studies published from 1955 to April 2015. If p<0.05 or I2 >50%, a random effect model was used to estimate overall relative risks (RRs) and 95% confidence intervals (CIs). Otherwise, a fixed effect model was applied. Publication bias was estimated using the funnel plot and Egger’s test. The doseresponse relationship was assessed using the method of restricted cubic splines with 4 knots at percentiles 5, 35, 65, and 95 of the distribution. The pooled RR of lung cancer for the highest versus lowest categories of dietary vitamin E intake was 0.84 (95% CI=0.76-0.93). With every 2 mg/d increase in dietary vitamin E intake, the risk of lung cancer statistically decreased by 5% (RR=0.95, 95% CI =0.91-0.99, plinearity=0.0237). Our analysis suggests that higher dietary vitamin E intake exerts a protective effect against lung cancer.

Read More

Vitamin E-coated dialysis membranes reduce the levels of oxidative genetic damage in hemodialysis patients.

Rodríguez-Ribera L, Corredor Z, Silva I, Díaz JM, Ballarín J, Marcos R, Pastor S, Coll E.

utat Res. 2017 Mar;815:16-21. doi: 10.1016/j.mrgentox.2017.01.003. Epub 2017 Feb 3.

Abstract

End-stage renal disease patients present oxidative stress status that increases when they are submitted to hemodialysis (HD). This increase in oxidative stress can affect their genetic material, among other targets. The objective of this study was to evaluate the effect of using polysulfone membranes coated with vitamin E, during the HD sessions, on the levels of genetic damage of HD patients. Forty-six patients were followed for 6 months, of whom 29 changed from conventional HD to the use of membranes coated with vitamin E. The level of genetic damage was measured using the micronucleus and the comet assays, both before and after the follow-up period. Serum vitamin E concentration was also checked. The obtained results showed that 24% of our patients presented vitamin E deficiency, and this was normalized in those patients treated with vitamin E-coated membranes. Patients with vitamin E deficiency showed higher levels of oxidative DNA damage. After the use of vitamin E-coated membranes we detected a significant decrease in the levels of oxidative damage. Additionally, hemoglobin values increased significantly with the use of vitamin E-coated membranes. In conclusion, the use of vitamin E-coated membranes supposes a decrease on the levels of oxidative DNA damage, and improves the uremic anemia status. Furthermore, the use of this type of membrane was also effective in correcting vitamin E deficiency.

Read More

Inhibitory Effects of γ- and δ-Tocopherols on Estrogen-Stimulated Breast Cancer In Vitro and In Vivo.

Bak MJ, Das Gupta S, Wahler J, Lee HJ, Li X, Lee MJ, Yang CS, Suh N.

Cancer Prev Res (Phila). 2017 Mar;10(3):188-197. doi: 10.1158/1940-6207.CAPR-16-0223. Epub 2017 Jan 17.

Abstract

Estrogens have been implicated as complete carcinogens for breast and other tissues through mechanisms involving increased cell proliferation, oxidative stress, and DNA damage. Because of their potent antioxidant activity and other effects, tocopherols have been shown to exert antitumor activities in various cancers. However, limited information is available on the effect of different forms of tocopherols in estrogen-mediated breast cancer. To address this, we examined the effects of α-, γ-, and δ-tocopherols as well as a natural γ-tocopherol-rich mixture of tocopherols, γ-TmT, on estrogen-stimulated MCF-7 cells in vitro and in vivo For the in vivo studies, MCF-7 cells were injected into the mammary fat pad of immunodeficient mice previously implanted with estrogen pellets. Mice were then administered diets containing 0.2% α-, γ-, δ-tocopherol, or γ-TmT for 5 weeks. Treatment with α-, γ-, δ-tocopherols, and γ-TmT reduced tumor volumes by 29% (P < 0.05), 45% (P < 0.05), 41% (P < 0.05), and 58% (P < 0.01), as well as tumor weights by 20%, 37% (P < 0.05), 39% (P < 0.05), and 52% (P < 0.05), respectively. γ- and δ-tocopherols and γ-TmT inhibited the expression of cell proliferation-related genes such as cyclin D1 and c-Myc, and estrogen-related genes such as TFF/pS2, cathepsin D, and progesterone receptor in estrogen-stimulated MCF-7 cells in vitro Further, γ- and δ-tocopherols decreased the levels of estrogen-induced oxidative stress and nitrosative stress markers, 8-hydroxy-2′-deoxyguanosine and nitrotyrosine, as well as the DNA damage marker, γ-H2AX. Our results suggest that γ- and δ-tocopherols and the γ-tocopherol-rich mixture are effective natural agents for the prevention and treatment of estrogen-mediated breast cancer.

Read More

Page 30 of 103« First...1020...2829303132...405060...Last »