Incorporation of tocopherol-rich extracts from mushroom mycelia into yogurt

Bouzgarrou C, Amara K , Reis FS , Barreira JCM , Skhiri F , Chatti N , Martins A , Barros L , Ferreira ICFR

Food Funct. 2018 Jun 20;9(6):3166-3172. doi: 10.1039/c8fo00482j.

Abstract

Consumers are well-informed about food additives and it is likely that they prefer natural additives over their synthetic analogues. Antioxidants represent a major class of food preservatives, among which tocopherols stand out as one of the most important examples. Interestingly, these compounds are present in relevant amounts in the mycelia of in vitro cultured mushrooms. Accordingly, the mycelia from Ganoderma lucidum, Pleurotus ostreatus and Pleurotus eryngii were used as alternative sources of tocopherols. These extracts were incorporated into different yogurt formulations, which were further compared among each other and with yogurts containing commercial α-tocopherol (E307), regarding their nutritional parameters, fatty acid profile and antioxidant activity. The proposed approach was validated as an effective functionalization strategy, particularly in the case of the G. lucidum mycelium, which showed the highest antioxidant potential, most likely as a result of its tocopherol profile. Furthermore, yogurts prepared with each mycelium extract allowed maintaining the nutritional properties observed in the “blank” yogurt formulation.

Wan Hasan WN, Abd Ghafar N, Chin KY, Ima-Nirwana S

Drug Des Devel Ther. 2018 Jun 13;12:1715-1726. doi: 10.2147/DDDT.S168935. eCollection 2018.

Abstract

PURPOSE:

Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis. However, detailed studies of the effects of AnTT on preosteoblastic cells were limited. This study was conducted to investigate the osteogenic effect of AnTT on preosteoblast MC3T3-E1 cells in a time-dependent manner.

MATERIALS AND METHODS:

Murine MC3T3-E1 preosteoblastic cells were cultured in the different concentrations of AnTT (0.001-1 µg/mL) up to 24 days. Expression of osteoblastic differentiation markers was measured by qPCR (osterix [OSX], collagen 1 alpha 1 [COL1α1], alkaline phosphatase [ALP], and osteocalcin [OCN]) and by fluorometric assay for ALP activity. Detection of collagen and mineralized nodules was done via Direct Red staining and Alizarin Red staining, respectively.

RESULTS:

The results showed that osteoblastic differentiation-related genes, such as OSX, COL1α1, ALP, and OCN, were significantly increased in the AnTT-treated groups compared to the vehicle group in a time-dependent manner (P<0.05). Type 1 collagen level was increased from day 3 to day 15 in the AnTT-treated groups, while ALP activity was increased from day 9 to day 21 in the AnTT-treated groups (P<0.05). Enhanced mineralization was observed in the AnTT-treated groups via increasing Alizarin Red staining from day 3 to day 21 (P<0.05).

CONCLUSION:

Our results suggest that AnTT enhances the osteogenic activity by promoting the bone formation-related genes and proteins in a temporal and sequential manner.

Ghlissi Z, Hakim A, Mnif H, Zeghal K, Rebai T, Boudawara T, Sahnoun Z

Saudi J Kidney Dis Transpl. 2018 May-Jun;29(3):545-553. doi: 10.4103/1319-2442.235168.

Abstract

This study was performed to investigate the protective effect of combined use of Vitamins E and C on colistin-induced tubular damage in rat. Animals were treated with sterile saline, colistin methanesulfonate (CMS), CMS + Vitamin E + Vitamin C, and Vitamin E + vitamin C, respectively, for seven days. Thereafter, animals were sacrificed and the urine N-acetyl-b-D-glucosaminidase (NAG) and gamma-glutamyl transferase (GGT) levels, plasma level of creatinine (Cr), vitamin E and vitamin C, and renal tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as renal histology were performed. CMS induced acute tubular necrosis, increased the NAG, GGT, and MDA levels, and reduced the Vitamin E, Vitamin C, SOD, CAT, and GPx activities. Co-treatment with vitamins E and C restored all biochemical parameters cited above and improved the histopathological damage. Tubular damage induced by colistin is at least partly due to oxidative stress. Nephroprotective effect of Vitamins E and C is partially mediated through its antioxidant properties, and the higher protection by the combination of these vitamins is related to its synergistic effects.

Sharma A, Kshetrimayum C, Sadhu HG, Kumar S

Environ Sci Pollut Res Int. 2018 Jun 8. doi: 10.1007/s11356-018-2398-z. [Epub ahead of print]

Abstract

Arsenic toxicity becomes one of the major public health issues in several countries. Chronic and acute exposure to arsenic has been reported to be toxic to various systems of the human body and also observed in controlled experimental studies. The study was conducted to evaluate the neurotoxic effect of arsenic in Swiss albino mice and its amelioration by Vitamin E, Coenzyme Q10 and their combination. Swiss albino mice were treated with arsenic of 136 ppm for 15 days. The daily dose is 1/3 of LD 50 (acute) reported dose of arsenic. Thereafter, the animals were maintained either on drinking water or treated with Vitamin E (50 mg/kg bwt), Coenzyme Q10 (10 mg/kg bwt), and their combination by i.p.daily for 15 days. After the treatment, animals were sacrificed. The weight of the brain was marginally lower (ns), in arsenic-treated group as compared to control and antioxidant-protected groups. The LPO (lipid peroxidation) level was higher in arsenic-treated group, and this elevation was checked to some extent by the selected antioxidants which were statistically significant in combination of antioxidant-protected group. A significant reduction was found in GSH (reduced glutathione) level in the brain of arsenic-treated mice whereas GSH level was considerably higher in antioxidant-protected groups. Further, total thiol and total protein level were lower in arsenic-treated group. However, total thiol was significantly higher in antioxidant-protected groups. CAT (catalase) activity was significantly lower while SOD (superoxide dismutase) activity was marginally lowered in arsenic-treated group, and it was slightly higher in antioxidant-protected groups. Further, reduction in AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) and motor coordination activity were also observed in arsenic-treated groups. Whereas, a higher AChE, BChE, and motor coordination activity was observed in antioxidant-protected group. These data indicate a positive role of selected antioxidant against the toxicity of arsenic in the brain of mice.

Kim Y, Gromovsky AD, Brown JM, Chung S

J Nutr Biochem. 2018 Jun 4;58:169-177. doi: 10.1016/j.jnutbio.2018.05.007. [Epub ahead of print]

Abstract

The activation of NLRP3 inflammasome in innate immune cells is associated with enhanced production of pro-inflammatory lipid mediator eicosanoids that play a crucial role in propagating inflammation. Gamma-tocotrienol (γT3) is an unsaturated vitamin E that has been demonstrated to attenuate NLRP3-inflammasome. However, the role of γT3 in regulating eicosanoid formation is unknown. We hypothesized that γT3 abolishes the eicosanoid production by modulating the macrophage lipidome. LPS-primed bone marrow-derived macrophages (BMDM) were stimulated with saturated fatty acids (SFA) along with γT3, and the effects of γT3 in modulating macrophage lipidome were quantified by using mass spectrometry based-shotgun lipidomic approaches. The SFA-mediated inflammasome activation induced robust changes in lipid species of glycerolipids (GL), glycerophospholipids (GPL), and sphingolipids in BMDM, which were distinctly different in the γT3-treated BMDM. The γT3 treatment caused substantial decreases of lysophospholipids (LysoPL), diacylglycerol (DAG), and free arachidonic acid (AA, C20:4), indicating that γT3 limits the availability of AA, the precursor for eicosanoids. This was confirmed by the pulse-chase experiment using [³H]-AA, and by diminished prostaglandin E₂ (PGE₂) secretion by ELISA. Concurrently, γT3 inhibited LPS-induced cyclooxygenases 2 (COX2) induction, further suppressing prostaglandin synthesis. In addition, γT3 attenuated ceramide synthesis by transcriptional downregulation of key enzymes for de novo synthesis. The altered lipid metabolism during inflammation is linked to reduced ATP production, which was partly rescued by γT3. Taken together, our work revealed that γT3 induces distinct modification of the macrophage lipidome to reduce AA release and corresponding lipid mediator synthesis, leading to attenuated cellular lipotoxicity.

Dixon P, Ghosh T, Mondal K, Konar A, Chauhan A, Hazra S

Drug Deliv Transl Res. 2018 Jun 1. doi: 10.1007/s13346-018-0541-5. [Epub ahead of print]

Abstract

Chemical injury by alkali burn is a major cause of corneal blindness in the clinical setting. Current management advocates multiple therapies aimed to prevent inflammation, initiate quick re-epithelialization, arrest the fibrosis, and avoid dry eye and pain by using bandage contact lenses. We hypothesized sustained delivery of the anti-inflammatory, antifibrotic drug pirfenidone through vitamin E-loaded contact lenses as a logical single approach to counter the pathology involved. Vitamin E particles were created in situ in commercial silicon hydrogel contact lenses by soaking the lenses in a vitamin E-ethanol solution. The vitamin E-laden lenses were then placed into pirfenidone-saline solution to load the drug into the lens. The contact lenses were evaluated by both in vitro and in vivo means. For in vitro, lenses were placed into 3 mL of saline solution. The concentration of pirfenidone released was measured by UV-vis spectrophotometry. The contact lenses were implanted in rabbit eyes following the alkali burn; the drug availability in the aqueous humor was evaluated by HPLC at various time points 10 min, 30 min, 2 h, and 3 h; and gene expression of inflammatory cytokines IL-1β, TNF-α, and TGF-β1 was evaluated in the cornea at the end of the study period. In another group of rabbits inflicted with alkali injury, the corneas were graded after 7 days of contact lens implantation with and without pirfenidone. A mathematical model was developed for delivery of the drug to the cornea and aqueous humor after a contact lens is inserted in the eye. The model was validated with experimental data and used to determine the bioavailability both for contact lenses and eye drops. In vitro release of unmodified commercial contact lenses saw a release time of approximately 20 min, with a partition coefficient of 2.68 ± 0.06. The release of pirfenidone from 20% vitamin E-loaded lenses saw a release time of approximately 80 min, with a partition coefficient of 4.20 ± 0.04. In vivo, the drug was available in the aqueous humor for up to 3 h. Gene expression of inflammatory cytokine IL-β1 and profibrotic growth factor TGF-β1 was significantly suppressed in corneas treated with pirfenidone contact lenses. A week after the alkali burn, the eyes with pirfenidone contact lenses showed significant improvement in corneal haze in comparison to the control eyes. About 50% of the drug loaded in the lens reached the aqueous humor compared to 1.3% with eye drops. Vitamin E-loaded contact lenses serve as a suitable platform for delivery of pirfenidone following alkali burn in rabbit eyes; positive pre-clinical outcome identifies it as promising therapy for addressing corneal inflammation and fibrosis. The bioavailability is about 40-fold higher for contact lenses compared to that for eye drops.

Nor Azman NHE, Goon JA, Abdul Ghani SM, Hamid Z, Wan Ngah WZ

Antioxidants (Basel). 2018 May 28;7(6). pii: E74. doi: 10.3390/antiox7060074.

Abstract

BACKGROUND:

Tocotrienol and tocopherol are known to prevent numerous degenerative diseases. The aim of this study is to compare the effects of tocotrienol-rich fraction (TRF) with α-tocopherol (α-TF) on the antioxidant status of healthy individuals aged between 50 and 55 years.

METHODS:

Volunteers were divided into groups receiving placebo (n = 23), α-TF (n = 24) and TRF (n = 24). Fasting venous blood samples were taken at baseline (0 month), 3 months and 6 months of supplementation for the determination of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities as well as for reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations.

RESULTS:

CAT and GPx were unaffected by TRF and α-TF supplementations. SOD activity increased significantly after six months of TRF supplementation. Analysis by gender showed that only female subjects had significant increases in SOD and GPx activities after six months of TRF supplementation. GPx activity was also significantly higher in females compared to males after six months of TRF supplementation. The GSH/GSSG ratio increased significantly after six months of TRF and α-TF supplementation in only the female subjects.

CONCLUSION:

TRF and α-TF supplementation exhibited similar effects to the antioxidant levels of older adults with TRF having more significant effects in females.

Rajagopalan P, Jain AP, Nanjappa V, Patel K, Mangalaparthi KK, Babu N, Cavusoglu N, Roy N, Soeur J, Breton L, Pandey A, Gowda H, Chatterjee A, Misra N

J Dermatol Sci. 2018 May 21. pii: S0923-1811(18)30215-9. doi: 10.1016/j.jdermsci.2018.05.003. [Epub ahead of print]

Abstract

BACKGROUND:

Skin acts as a protective barrier against direct contact with pollutants but inhalation and systemic exposure have indirect effect on keratinocytes. Exposure to diesel exhaust has been linked to increased oxidative stress.

OBJECTIVE:

To investigate global proteomic alterations in diesel particulate extract (DPE)/its vapor exposed skin keratinocytes.

METHODS:

We employed Tandem Mass Tag (TMT)-based proteomics to study effect of DPE/DPE vapor on primary skin keratinocytes.

RESULTS:

We observed an increased expression of oxidative stress response protein NRF2, upon chronic exposure of primary keratinocytes to DPE/its vapor which includes volatile components such as polycyclic aromatic hydrocarbons (PAHs). Mass spectrometry-based quantitative proteomics led to identification 4490 proteins of which 201 and 374 proteins were significantly dysregulated (≥1.5 fold, p ≤ 0.05) in each condition, respectively. Proteins involved in cellular processes such as cornification (cornifin A), wound healing (antileukoproteinase) and differentiation (suprabasin) were significantly downregulated in primary keratinocytes exposed to DPE/DPE vapor. These results were corroborated in 3D skin models chronically exposed to DPE/DPE vapor. Bioinformatics analyses indicate that DPE and its vapor affect distinct molecular processes in skin keratinocytes. Components of mitochondrial oxidative phosphorylation machinery were seen to be exclusively overexpressed upon chronic DPE vapor exposure. In addition, treatment with an antioxidant like vitamin E partially restores expression of proteins altered upon exposure to DPE/DPE vapor.

CONCLUSIONS:

Our study highlights distinct adverse effects of chronic exposure to DPE/DPE vapor on skin keratinocytes and the potential role of vitamin E in alleviating adverse effects of environmental pollution.

Aghadavod E, Soleimani A, Hamidi G, Keneshlou F, Heidari A, Asemi Z

Iran J Kidney Dis. 2018 May;12(3):156-162.

Abstract

INTRODUCTION:

Patients with diabetic nephropathy (DN) may benefit from vitamin E‘s antilipid and antioxidant activities. This study aimed to evaluate the effects of high-dose vitamin E supplementation on markers of cardiometabolic risk and oxidative stress in patients with DN.

MATERIALS AND METHODS:

This randomized controlled trial was carried out on 54 patients with DN that were randomly divided into 2 groups to receive vitamin E supplement (800 IU/d) or placebo for 12 weeks. Fasting blood samples were obtained at baseline and after the 12-week intervention to determine markers of cardiometabolic risk and oxidative stress.

RESULTS:

Vitamin E supplementation, compared with the placebo, resulted in a significant reduction in serum total cholesterol (-14.3 ± 29.9 mg/dL versus -0.8 ± 13.1 mg/L, P = .03), low-density lipoprotein cholesterol (-16.4 ± 28.5 mg/dL versus 0.1 ± 17.2 mg/L, P = .01), and ratio of total cholesterol to high-density lipoprotein cholesterol ratio (-0.5 ± 0.7 versus 0.1 ± 0.5, P = .001), and a significant elevation in vitamin Elevels (39.7 ± 12.4 nmol/mL versus -0.5 ± 1.3 nmol/mL, P < .001) and high-density lipoprotein cholesterol levels (1.4 ± 3.7 versus -2.1 ± 5.1 mg/L, P = .006). It also resulted in a significant elevation in plasma glutathione levels.

CONCLUSIONS:

Our study demonstrated that high-dose vitamin E supplementation for 12 weeks had favorable effects on lipid profile and glutathione levels of patients with DN, except for triglycerides, very low-density lipoprotein cholesterol, nitric oxide, and total antioxidant capacity levels.

Abraham A, Kattoor AJ, Saldeen T, Mehta JL.

Crit Rev Food Sci Nutr. 2018 May 10:1-23. doi: 10.1080/10408398.2018.1474169. [Epub ahead of print]

Abstract

Vitamin E is a lipid soluble vitamin comprising of eight natural isoforms, namely, α, β, δ, γ isoforms of tocopherol and α, β, δ, γ isoforms of tocotrienol. Many studies have been performed to elucidate its role in cancer. Until last decade, major focus was on alpha tocopherol and its anticancer effects. However, major clinical trials using alpha-tocopherol like SELECT trial and ATBC trial did not yield meaningful results. Hence there was a shift of focus to gamma-tocopherol, delta-tocopherol and tocotrienol. Unlike alpha-tocopherol, gamma-tocopherol and delta-tocopherol can scavenge reactive nitrogen species in addition to reactive oxygen species. Antiangiogenic effect, inhibition of HMG CoA reductase enzyme and inhibition of NF-κB pathway make the anti-cancer effects of tocotrienols unique compared to other vitamin E isoforms. Preclinical research on non-alpha tocopherol isoforms of vitamin E showed promising data on their anticancer effects. In this review, we deal with the current understanding on the potential mechanisms involved in the anticancer effects of vitamin E and the controversies in this field over last three decades. We also highlight the need to conduct further research on the anticancer effects of non-alpha-tocopherol isoforms in larger population and clinical setting.

KEYWORDS:

Vitamin E and cancer; anticancer mechanisms; tocopherol; tocopherol and cancer; tocotrienol