Mitochondria have emerged recently as effective targets for novel anti-cancer drugs referred to as ‘mitocans’. We propose that the molecular mechanism of induction of apoptosis by mitocans, as ...exemplified by the drug α-tocopheryl succinate, involves generation of reactive oxygen species (ROS). ROS then mediate the formation of disufide bridges between cytosolic Bax monomers, resulting in the formation of mitochondrial outer membrane channels. ROS also cause oxidation of cardiolipin, triggering the release of cytochrome
c and its translocation via the activated Bax channels. This model may provide a general mechanism for the action of inducers of apoptosis and anticancer drugs, mitocans, targeting mitochondria via ROS production.
Individuals with both diabetes mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype are at increased risk of cardiovascular disease. As the antioxidant function of the Hp 2-2 protein is impaired, we ...sought to test the pharmacogenomic hypothesis that antioxidant vitamin E supplementation would provide cardiovascular protection to Hp 2-2 DM individuals.
We determined the Hp genotype on DM participants from two trials (HOPE and ICARE) and assessed the effect of vitamin E by Hp genotype on their common prespecified outcome, the composite of stroke, myocardial infarction and cardiovascular death. Data was analyzed with a fixed-effect model. These results were input into a simulation model, the Evidence Based Medicine Integrator, in order to estimate their long-term implications in a real-world population from Kaiser Permanente (CA, USA).
Meta-analysis of the two trials demonstrated a significant overall reduction in the composite end point in Hp 2-2 DM individuals with vitamin E (odds ratio: 0.58; 95% CI: 0.40-0.86; p = 0.006). There was a statistically significant interaction between the Hp genotype and vitamin E on the composite end point. In these trials, Hp typing of 69 DM individuals and treating those with the Hp 2-2 with vitamin E prevented one myocardial infarct, stroke or cardiovascular death. Lifelong administration of vitamin E to Hp 2-2 DM individuals in the Kaiser population would increase their life expectancy by 3 years.
A pharmacogenomic strategy of screening DM individuals for the Hp genotype and treating those with Hp 2-2 with vitamin E appears to be highly clinically effective.
Ferulic acid is a potent ubiquitous plant antioxidant. Its incorporation into a topical solution of 15% L-ascorbic acid and 1% α-tocopherol improved chemical stability of the vitamins (C+E) and ...doubled photoprotection to solar-simulated irradiation of skin from 4-fold to approximately 8-fold as measured by both erythema and sunburn cell formation. Inhibition of apoptosis was associated with reduced induction of caspase-3 and caspase-7. This antioxidant formulation efficiently reduced thymine dimer formation. This combination of pure natural low molecular weight antioxidants provides meaningful synergistic protection against oxidative stress in skin and should be useful for protection against photoaging and skin cancer.
Abstract The aim of this work was to develop a new type of d -alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) coated multi-functional (theranostic) liposomes, which contain both ...docetaxel and quantum dots (QDs) for cancer imaging and therapy. Non-targeting and folate receptor targeting TPGS coated theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential, surface chemistry and drug encapsulation efficiency. MCF-7 breast cancer cells of folate receptor overexpression were employed as an in vitro model to assess cellular uptake and cytotoxicity of the drug and QDs loaded liposomes. The mean particle size of the non-targeting and the targeting liposomes was found to be 202 and 210 nm, respectively. High resolution field emission transmission electron microscopy (FETEM) confirmed the presence of quantum dots in the peripheral hydrophobic membranes of the liposomes. The qualitative internalization of multi-functional liposomes by MCF-7 cells was visualized by confocal laser scanning microscopy (CLSM). The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 9.54 ± 0.76, 1.56 ± 0.19 and 0.23 ± 0.05 μg/ml for the commercial Taxotere® , non-targeting and targeting liposomes, respectively after 24 h culture with MCF-7 cells. The targeting multi-functional liposomes showed greater efficacy than the non-targeting liposomes and thus great potential to improve the cancer imaging and therapy.
Solid lipid nanoparticles (SLNs) have several potential applications in the topical drug delivery. The current project aimed to prepare and characterize SLNs loaded with vitamin E for topical ...administration and incorporating the prepared SLNs in a cream base. Further, the permeation of prepared SLNs was studied through a synthetic membrane and the release profiles were compared with vitamin E cream. The prepared SLNs were subjected to stability studies at two different temperatures. Hot homogenization followed by dilution technique was used for the preparation of SLNs. In this project, PDMS membrane was used to mimic the skin for permeation studies. From the results of this study, it can be concluded that prepared SLNs had enhanced the permeation of vitamin E as compared to vitamin E cream.
•Alpha-tocopherol quinine ameliorates spatial memory deficits in AD transgenic mice.•Alpha-tocopherol quinine decreases Aβ oligomer levels in the brain of AD transgenic mice.•Alpha-tocopherol quinine ...inhibits microglia activation by inhibiting NF-κB signaling pathway.•Alpha-tocopherol quinine reduces cytokine production and oxidative stress in AD mice.•Alpha-tocopherol quinine has potential therapeutic value for AD treatment.
The pathologies of Alzheimer's disease (AD) is associated with soluble beta-amyloid (Aβ) oligomers, neuroinflammation and oxidative stress. Decreasing the levels of Aβ oligomer, glial activation and oxidative stress are potential therapeutic approaches for AD treatment. We previously found alpha-tocopherol quinine (α-TQ) inhibited Aβ aggregation and cytotoxicity, decreased the release of inflammatory cytokines and reactive oxygen species (ROS) in vitro. However, whether α-TQ ameliorates memory deficits and other neuropathologies in mice or patients with AD remains unknown. In this study, we reported that orally administered α-TQ ameliorated memory impairment in APPswe/PS1dE9 transgenic mice, decreased oxidative stress and the levels of Aβ oligomer in the brains of mice, prevented the production of inducible nitric oxide synthase and inflammatory mediators, such as interleukin-6 and interleukin-1β, and inhibited microglial activation by inhibiting NF-κB signaling pathway. These findings suggest that α-TQ has potential therapeutic value for AD treatment.
An environmentally benign surfactant (TPGS-750-M), a diester composed of racemic α-tocopherol, MPEG-750, and succinic acid, has been designed and readily prepared as an effective nanomicelle-forming ...species for general use in metal-catalyzed cross-coupling reactions in water. Several "name" reactions, including Heck, Suzuki-Miyaura, Sonogashira, and Negishi-like couplings, have been studied using this technology, as have aminations, C-H activations, and olefin metathesis reactions. Physical data in the form of DLS and cryo-TEM measurements suggest that particle size and shape are key elements in achieving high levels of conversion and, hence, good isolated yields of products. This new amphiphile will soon be commercially available.
Oxidative stress is implicated in both hypo- and hyper-thyroid conditions. In the present study an attempt has been made to elucidate possible interaction between vitamin E or/and curcumin (two ...established antioxidants) with active portion (redox signaling intervening region) of nuclear factor erythroid 2-related factor 2 (NRF2) as a mechanism to alleviate oxidative stress in rat heart under altered thyroid states. Fifty Wistar strain rats were divided into two clusters (Cluster A: hypothyroidism; Cluster B: hyperthyroidism). The hypo- (0.05% (w/v) propylthiouracil in drinking water) and hyper- (0.0012% (w/v) T4 in drinking water) thyroid rats in both clusters were supplemented orally with antioxidants (vitamin E or/and curcumin) for 30 days. Interactive least count difference and principal component analyses indicated increase in lipid peroxidation, reduced glutathione level, alteration in the activities and protein expression of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase under altered thyroid states. However, the expression of stress survival molecules; nuclear factor κB (NFκB) and the serine-threonine kinase B (Akt), in hyper-thyroidism only points towards different mechanisms responsible for either condition. Co-administration of vitamin E and curcumin showed better result in attenuating expression of mammalian target for rapamycin (mTOR), restoration of total protein content and biological activity of Ca
ATPase in hyperthyroid rats, whereas, their individual treatment showed partial restoration. Since NRF2 is responsible for activation of antioxidant response element and subsequent expression of antioxidant enzymes, possible interactions of both vitamin E or/and curcumin with the antioxidant enzymes, NRF2 and its regulator Kelch ECH associating protein (KEAP1) were studied in silico. For the first time, a modeled active portion of the zipped protein NRF2 indicated its interaction with both vitamin E and curcumin. Further, curcumin and vitamin E complex showed in silico interaction with KEAP1. Reduction of oxidative stress by curcumin and/or vitamin E may be due to modulation of NRF2 and KEAP1 function in rat heart under altered thyroid states.
The present study was designed to find the effect of natural and synthetic antioxidants on the performance of two broiler strains under high ambient temperature. A total of 320 day-old chicks of ...Hubbard and Cobb were reared for a period for 21 days under the same nutritional and management systems. On day 21 onward, one subgroup was kept as control while other subgroups were provided with vitamin E (250 mg/kg), ginger (2 g/kg), and
l
-carnitine (500 mg/kg) in basal diets. Body weight and feed conversion ratio (FCR) were significantly (
P
< 0.05) high in vitamin E-supplemented birds, while feed intake was significantly (
P
< 0.05) higher in
l
-carnitine supplemented birds irrespective of the strain. Antibody titer against infectious bursal disease (IBD) and paraoxonase (PON1) was significantly (
P
< 0.05) higher in vitamin E-supplemented birds compared to the other treatments. The number of heterophils and toal oxidant status (TOS) were significantly (
P
< 0.05) lower in vitamin E-supplemented birds. Blood glucose was significantly (
P
< 0.05) lower in vitamin E-supplemented birds, while total protein was significantly (
P
< 0.05) higher in vitamin E-supplemented group. In conclusion, the supplementation of vitamin E at the rate of 250 mg/kg improved the antioxidant status and immune response in the two broiler strains. Further, the two strains perform similarly in terms of performance and other health status parameters with no significant difference.
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