The inhibitor-evoked shortage of tocopherol and plastoquinol is compensated by other antioxidant mechanisms in Chlamydomonas reinhardtii exposed to toxic concentrations of cadmium and chromium ions

Nowicka B, Fesenko T, Walczak J, Kruk J

Ecotoxicol Environ Saf. 2020 Mar 15;191:110241. doi: 10.1016/j.ecoenv.2020.110241. Epub 2020 Jan 31.

Abstract

One of the major mechanisms of heavy metal toxicity is the induction of oxidative stress. Redox-active heavy metals, like chromium, can induce it directly, whereas redox-inactive metals, like cadmium, play an indirect role in the generation of reactive oxygen species (ROS). Living organisms defend themselves against oxidative stress taking advantage of low-molecular-weight antioxidants and ROS-detoxifying enzymes. Tocopherols and plastoquinol are important plastid prenyllipid antioxidants, playing a role during acclimation of Chlamydomonas reinhardtii to heavy metal-induced stress. However, partial inhibition of synthesis of these prenyllipids by pyrazolate did not decrease the tolerance of C. reinhardtii to Cr- and Cd-induced stress, suggesting redundancy between antioxidant mechanisms. To verify this hypothesis we have performed comparative analyses of growth, photosynthetic pigments, low-molecular-weight antioxidants (tocopherols, plastoquinol, plastochromanol, ascorbate, soluble thiols, proline), activities of the ascorbate peroxidase (APX), catalase and superoxide dismutase (SOD) and cumulative superoxide production in C. reinhardtii exposed to Cd2+ and Cr2O72- ions in the presence or absence of pyrazolate. The decreased α-tocopherol and plastoquinol content resulted in the increase in superoxide generation and APX activity in pyrazolate-treated algae. The application of heavy metal ions and pyrazolate had a pronounced impact on Asc and total thiol content, as well as SOD and APX activities (the latter only in Cd-exposed cultures), when compared with algae grown in the presence of heavy metal ions or pyrazolate alone. The superoxide production in cultures exposed to heavy metal ions and pyrazolate decreased when compared to the cultures exposed to either heavy metal ions or an inhibitor alone.

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Retinol and α-tocopherol in pregnancy: Establishment of reference intervals and associations with CBC

Liu J, Zhan S, Jia Y, Li Y, Liu Y, Dong Y, Tang G, Li L, Zhai Y, Cao Z

Matern Child Nutr. 2020 Mar 5:e12975. doi: 10.1111/mcn.12975. [Epub ahead of print]

Abstract

Profound physiological changes during pregnancy may affect the requirement of retinol and tocopherol, which are essential micronutrients for the maintenance of maternal health and foetal development. However, the current reference intervals (RIs) of retinol and tocopherol are based on non-pregnant population. In the present study, a liquid chromatography-tandem mass spectrometry quantitation method for serum retinol and α-tocopherol was established and validated. In addition, we established trimester-specific RIs of retinol and α-tocopherol using the data from paired screening test for 31,301 outpatients who participated in the prenatal vitamins A/E evaluation program at our hospital using the Hoffmann method, which is a simple indirect RI estimation method that does not require the recruitment of healthy subjects. Further, to explore the associations between the levels of retinol and α-tocopherol and the parameters of complete blood count (CBC), the results of retinol, α-tocopherol, and CBC of 1,977 pregnant outpatients in the third trimester were analysed. The testing interval between the levels of vitamins and CBC was no more than 7 days. Although no significant changes were noticed in the levels of retinol, the α-tocopherol levels continuously increased with normal physiological changes throughout pregnancy. Lower retinol levels were associated with the higher incidence of anaemia, whereas higher levels of retinol and lower levels of α-tocopherol were associated with higher platelet count.

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Role of α-tocopherol and Lactobacillus plantarum in the alleviation of mercuric chloride-induced testicular atrophy in rat’s model: Implication of molecular mechanisms

Fadda LM, Alhusaini AM, Al-Qahtani QH, Ali HM, Hasan IH

J Biochem Mol Toxicol. 2020 Mar 5:e22481. doi: 10.1002/jbt.22481. [Epub ahead of print]

Abstract

The present work was aimed to evaluate the protective effects of alpha-tocopherol (α-toco) and/or Lactobacillus plantarum (LCB) against testicular atrophy induced by mercuric chloride (MCH). Rats were injected with 5 mg/kg MCH for 5 days consecutively, then treated with 100 mg/kg α-toco and 6 × 1010 CFU 1.8701/kg LCB alone or together for 3 weeks. The MCH elevated serum TNF-α, IL- 6, caspase-3, and testicular malondialdehyde. However, serum testosterone, dehydroepiandrosterone, testicular messenger RNA of a steroidogenic acute regulatory protein, 17-β-hydroxysteroid dehydrogenase, 3β-hydroxysteroid dehydrogenase, glutathione level, and superoxide dismutase activity were decreased. Protein expression of Nrf2 was downregulated whereas that of Bax and DNA fragmentation was upregulated in the testicular tissues. Treatment with α-toco and LCB ameliorated the deviated biochemical parameters and improved tissue injury. It was concluded that the combination of LCB and α-toco achieved promising results in the amelioration of MCH-induced testicular atrophy. Nrf2, Bax expressions, and DNA fragmentation are involved in the testicular atrophy induced by MCH.

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Fatty acids based α-Tocopherol loaded nanostructured lipid carrier gel: In vitro and in vivo evaluation for moisturizing and anti-aging effects

Ijaz M, Akhtar N

J Cosmet Dermatol. 2020 Mar 4. doi: 10.1111/jocd.13346. [Epub ahead of print]

Abstract

BACKGROUND:

α-Tocopherol is a potent antioxidant present in the skin. Its concentration decreases with age. Synthetically available α-tocopherol is viscous, irritating to skin and unstable toward oxidation and ultraviolet (UV) light.

AIMS:

To develop fatty acids based nanostructured lipid carrier (NLC) gel loaded with α-tocopherol and to evaluate its moisturizing and anti-aging properties.

METHODS:

Lauric acid, oleic acid, and Tween-80 were used as solid lipid, liquid lipid, and surfactant, respectively. Seven formulations (F0-F6) were developed by using different concentration of ingredients. Most optimized formulation (F2) was selected for further study on the basis of characterization. Dialysis tube method was used for release study. F2 was incorporated in gel, and then, in vitro and noninvasive in vivo study regarding skin moisture content by corneometer® and skin mechanical properties by cutometer® for 12 weeks on human volunteers (n = 13) was conducted.

RESULTS:

Size, polydispersibility index (PDI), zeta potential, and %entrapment efficiency (%EE) of optimized formulation (F2) were found 82 nm, 0.261, -28.6, and 94.88 ± 1.16, respectively. Particles were spherical in shape. The release profile showed initial burst and then sustained release, and release data were best fitted to weibull model. α-tocopherol loaded NLC gel (NLCG) appeared physically stable for 12 weeks at room temperature and showed significant results in terms of skin capacitance and mechanical properties. Rheological assessment showed non-Newtonian behavior.

CONCLUSION:

Fatty acids based NLC proved to be a promising carrier of photochemically unstable lipophilic vitamin E with enhanced moisturizing and anti-aging properties.

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UPLC-MS/MS method for determination of retinol and α-tocopherol in serum using a simple sample pretreatment and UniSpray as ionization technique to reduce matrix effects

Peersman N, Elslande JV, Lepage Y, De Amicis S, Desmet K, Vermeersch P

Clin Chem Lab Med. 2020 Mar 2. pii: /j/cclm.ahead-of-print/cclm-2019-1237/cclm-2019-1237.xml. doi: 10.1515/cclm-2019-1237. [Epub ahead of print]

Abstract

Background Our goal was to develop a simple, rapid and precise ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of retinol and α-tocopherol in serum. Currently published LC-MS/MS methods either require complex extraction procedures (liquid-liquid or solid-phase) or do not meet desirable specifications for imprecision in serum (coefficient of variation [CV] <6.8% and 6.9%, respectively). Methods Sample preparation consisted of a simple protein precipitation with ethanol and acetonitrile. Stable isotope-labeled internal standards (IS) and a homemade calibration curve were used for quantification. The analysis was performed using an Acquity I-class Xevo TQ XS LC-MS/MS. Chromatographic runtime was 6.0 min using a reversed phase gradient elution. UniSpray (US) as an ionization technique was compared to electrospray ionization (ESI). Analytical validation included matrix effect, recovery and trueness compared to National Institute of Standards and Technology (NIST) standards and United Kingdom National External Quality Assessment Service (UK NEQAS) samples. Results Intra- and inter-run CVs were <4.9% for retinol and <1.7% for α-tocopherol, both complying with desirable specifications for imprecision. Bias compared to NIST standards was <3.1% for both compounds. The method was linear over the entire tested range. The lower limit of quantification (LLOQ) with US was lower than with ESI for both retinol (0.022 vs. 0.043 mg/L) and α-tocopherol (0.22 vs. 0.87 mg/L). Matrix effects were not significant (<15%) for retinol. However, for α-tocopherol matrix effects of on average 54.0% were noted using ESI, but not with US. Conclusions We developed a fast, precise and accurate UPLC-MS/MS method for the determination of retinol and α-tocopherol in human serum using a single-step sample pretreatment. Ionization using US eliminated the matrix effects for α-tocopherol.

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Alpha lipoic acid and vitamin E improve atorvastatin-induced mitochondrial dysfunctions in rats

Eser Faki H, Tras B, Uney K

Mitochondrion. 2020 Feb 28;52:83-88. doi: 10.1016/j.mito.2020.02.011. [Epub ahead of print]

Abstract

To determine the effects of alpha lipoic acid (ALA) and vitamin E (Vit E) on mitochondrial dysfunction caused by statins. A total of 38 Wistar Albino rats were used in this study. The control group received dimethyl sulfoxide. The atorvastatin (A) group received atorvastatin (10 mg/kg). The A + ALA group received atorvastatin (10 mg/kg) and ALA (100 mg/kg). The A + Vit E group was administered atorvastatin (10 mg/kg) and Vit E (100 mg/kg). The A + ALA + Vit E group was administered atorvastatin (10 mg/kg), ALA (100 mg/kg) and Vit E (100 mg/kg). All applications were administered simultaneously by gavage for 20 days. ATP level and complex I activity were measured from liver, muscle, heart, kidney and brain. Atorvastatin significantly decreased the ATP levels in heart and kidney, while a slight decrease was seen in liver, muscle and brain. Atorvastatin caused an insignificant decrease in the complex I activity in all tissues examined. ALA administration significantly improved the ATP levels in the liver, heart and kidney, while Vit E improved the ATP levels in all tissues except the muscle compared to Atorvastatin group. Single administration of both ALA and vit E ameliorated complex I activity in the muscle, heart, kidney and brain. The combination of ALA and Vit E significantly improved the ATP levels in the liver, heart, kidney and brain and also provided significant improvements the complex I activity in all tissues. The undesirable effects of Atorvastatin on mitochondrial functions in this study ameliorated by using ALA and/or Vit E alone and in combination.

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Differential Effects of MitoVitE, α-Tocopherol and Trolox on Oxidative Stress, Mitochondrial Function and Inflammatory Signalling Pathways in Endothelial Cells Cultured under Conditions Mimicking Sepsis

Minter BE, Lowes DA, Webster NR, Galley HF

Antioxidants (Basel). 2020 Feb 26;9(3). pii: E195. doi: 10.3390/antiox9030195.

Abstract

Sepsis is a life-threatening response to infection associated with inflammation, oxidative stress and mitochondrial dysfunction. We investigated differential effects of three forms of vitamin E, which accumulate in different cellular compartments, on oxidative stress, mitochondrial function, mRNA and protein expression profiles associated with the human Toll-like receptor (TLR) -2 and -4 pathways. Human endothelial cells were exposed to lipopolysaccharide (LPS)/peptidoglycan G (PepG) to mimic sepsis, MitoVitE, α-tocopherol, or Trolox. Oxidative stress, mitochondrial function, mitochondrial membrane potential and metabolic activity were measured. NFκB-P65, total and phosphorylated inhibitor of NFκB alpha (NFκBIA), and STAT-3 in nuclear extracts, interleukin (IL)-6 and IL-8 production in culture supernatants and cellular mRNA expression of 32 genes involved in Toll-like receptor-2 and -4 pathways were measured. Exposure to LPS/PepG caused increased total radical production (p = 0.022), decreased glutathione ratio (p = 0.016), reduced membrane potential and metabolic activity (both p < 0.0001), increased nuclear NFκB-P65 expression (p = 0.016) and increased IL-6/8 secretion (both p < 0.0001). MitoVitE, α- tocopherol and Trolox were similar in reducing oxidative stress, NFκB activation and interleukin secretion. MitoVitE had widespread downregulatory effects on gene expression. Despite differences in site of actions, all forms of vitamin E were protective under conditions mimicking sepsis. These results challenge the concept that protection inside mitochondria provides better protection.

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Bladder cancer: total antioxidant capacity and pharmacotherapy with vitamin-E

Mazdak H, Tolou Ghamari Z, Gholampour M

Int Urol Nephrol. 2020 Feb 22. doi: 10.1007/s11255-020-02411-3. [Epub ahead of print]

Abstract

PURPOSE:

Free radicals play an important role in the different complex course of carcinogenesis. Higher concentrations of reactive oxygen species are highly associated with the presence of tumors. The urinary bladder organ is also a target for many carcinogens. The major objective of this investigation was to measure the role of redox state or total antioxidant capacity (T-AOC) and antioxidant functions of vitamin E in patients with low-grade papillary cancer of the bladder (BC).

METHODS:

The blood sample was used for measurement of the T-AOC by the Trolox-TAC assay kit. Thirty-five patients with BC and thirty-five healthy subjects that matched for age were entered in this study. The obtained data were analyzed using the Statistical Package (SPSS Inc, Chicago, IL, USA). The significance level was set at p ≤ 0.05.

RESULTS:

In healthy controls, the mean ± SD for T-AOC was 91.8 ± 16.6 (U/ml), that was significantly higher when compared to the mean value of 24.5 ± 28.9 (U/ml) in patients with BC (p = 0.00). The difference in concentration of T-AOC before and after prescription of vitamin E was encountered with a p value of 0.16.

CONCLUSIONS:

By reference to the significant difference between T-AOC in patients and healthy controls, our results strongly suggest a low level of T-AOC in patients with BC. The obtained changes in T-AOC before and after management with vitamin E recommended additional consideration associates with different stages and grade of tumor in patients with BC.

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Antioxidant supplements and endurance exercise: Current evidence and mechanistic insights

Mason SA, Trewin AJ, Parker L, Wadley GD

Redox Biol. 2020 Feb 20:101471. doi: 10.1016/j.redox.2020.101471. [Epub ahead of print]

Abstract

Antioxidant supplements are commonly consumed by endurance athletes to minimize exercise-induced oxidative stress, with the intention of enhancing recovery and improving performance. There are numerous commercially available nutritional supplements that are targeted to athletes and health enthusiasts that allegedly possess antioxidant properties. However, most of these compounds are poorly investigated with respect to their in vivo redox activity and efficacy in humans. Therefore, this review will firstly provide a background to endurance exercise-related redox signalling and the subsequent adaptations in skeletal muscle and vascular function. The review will then discuss commonly available compounds with purported antioxidant effects for use by athletes. N-acetyl cysteine may be of benefit over the days prior to an endurance event; while chronic intake of combined 1000 mg vitamin C + vitamin E is not recommended during periods of heavy training associated with adaptations in skeletal muscle. Melatonin, vitamin E and α-lipoic acid appear effective at decreasing markers of exercise-induced oxidative stress. However, evidence on their effects on endurance performance are either lacking or not supportive. Catechins, anthocyanins, coenzyme Q10 and vitamin C may improve vascular function, however, evidence is either limited to specific sub-populations and/or does not translate to improved performance. Finally, additional research should clarify the potential benefits of curcumin in improving muscle recovery post intensive exercise; and the potential hampering effects of astaxanthin, selenium and vitamin A on skeletal muscle adaptations to endurance training. Overall, we highlight the lack of supportive evidence for most antioxidant compounds to recommend to athletes.

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Dietary Lipid Intake Influences the Alpha-Tocopherol Levels in Human Milk

da Mata AMB, da Silva AGCL, Medeiros JFP, Lima MSR, Bezerra DS, da Silva AB, Osório MM, Dimenstein R, da Silva Ribeiro KD

J Pediatr Gastroenterol Nutr. 2020 Feb 19. doi: 10.1097/MPG.0000000000002668. [Epub ahead of print]

Abstract

OBJECTIVE:

Dietary lipid intake is associated with serum alpha-tocopherol levels; however, its impact on human milk is unknown. The objective of this study was to evaluate the relationship between maternal intake of vitamin E, lipids, and fatty acids and the concentration of alpha-tocopherol in human milk.

METHODS:

We conducted a longitudinal observational study, including 143 lactating women on 7, 30, and 90 days postpartum. Dietary intake was collected using 24-hour recall. On day 90, a human milk sample was collected and analyzed for alpha-tocopherol concentration. The prevalence of inadequate vitamin E intake was determined by the Estimated Average Requirement (16 mg/day), and the alpha-tocopherol concentration was analyzed by high-performance liquid chromatography.

RESULTS:

Dietary intake of vitamin E was associated with the intake of lipids (r = 0.237, P = 0.004) and fatty acids (P < 0.05), and 100% of the participants had inadequate vitamin intake. Mean alpha-tocopherol concentration in the human milk samples was 7.11 (SD 3.95) μmol/L and was correlated with lipid (r = 0.201, P = 0.042) and polyunsaturated fatty acid intake (r = 0.235, P = 0.017). Higher vitamin E levels were found in participants with the highest quartile of polyunsaturated fatty acid intake.

CONCLUSIONS:

Alpha-tocopherol concentration was associated with the dietary intake of lipids and fatty acids, demonstrating that its bioavailability is associated with fats in the mammary gland. These results suggest development of appropriate strategies to increase the levels of vitamin E in breast milk that may help to prevent and treat vitamin E deficiency.

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