Phytochemical Profiles of Rice and Their Cellular Antioxidant Activity Against ABAP Induced Oxidative Stress in Human Hepatocellular Carcinoma HepG2 Cells

Er Sheng Gong, Chengmei Liu, Bin Li, Wei Zhou, Hongyu Chen, Tong Li, Jianyong Wu, Zicong Zeng, Yuehua Wang, Xu Si, Yuxi Lang, Ye Zhang, Weijia Zhang, Guowen Zhang, Shunjing Luo, Rui Hai Liu

Food Chem . 2020 Jul 15;318:126484. doi: 10.1016/j.foodchem.2020.126484. Epub 2020 Feb 25.


The phytochemical contents, peroxyl radical scavenging capacities (PSCs) and cellular antioxidant activities (CAAs) of free and bound fractions of rice were reported. Black rice had the highest total phenolic content and total flavonoid content in free and bound fractions, followed by red rice, brown rice, and polished rice. Black rice contained much more free phenolic compounds than other rice samples, such as cyanidin-3-O-glucoside, protocatechuic acid, and vanillic acid. Tocopherols and tocotrienols contents were highest in red rice, then in black rice, brown rice, and polished rice. PSCs and CAAs of free and bound fractions were in the order: black rice > red rice > brown rice > polished rice, except that bound CAA of red rice was higher than that of black rice. The cellular uptake rate of free phenolics was highest in red rice, while cellular uptake rates of bound phenolics were highest in brown rice and polished rice.

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A Novel Combination of γ-Tocopherol-Rich Mixture of Tocopherols and Ascorbic Acid Restores Fertility in Cases of Tyrosine Nitration-Associated Male Infertility in Mice

Eleonora Scarlata, Maria C Fernandez, Cristian O'Flaherty

Antioxidants (Basel) . 2020 Jul 13;9(7):E613. doi: 10.3390/antiox9070613.


Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for 50% of the cases. Currently, a physical examination, hormone profiling and the evaluation of two consecutive semen samples (to determine the sperm concentration, motility, morphology and, in very few cases, sperm DNA integrity) are the sole tools that physicians have to evaluate infertility in men. Antioxidant therapy is often used to improve sperm quality and function in infertile men. However, there are controversial results regarding the efficacy of these treatments. Prdx6-/- male mice are subfertile, displaying significant oxidative damage in the lipids, proteins and DNA of their spermatozoa. Here, we used Prdx6-/- male mice to test whether a novel combination of tocopherols that contained 60% γ-tocopherol and ascorbic acid could restore their fertility. These mice were fed with the supplemented (Vit. Mix) or control diets. To assess sperm quality, we determined the motility, levels of lipid peroxidation, DNA oxidation and tyrosine nitration in the spermatozoa. The number of pups sired by the Prdx6-/- mice fed with the Vit. Mix diet was higher than that sired by the males fed with the control diet, and the pups’ mortality was lower. The sperm quality was improved in the males fed with the supplemented diet. We concluded that treatment with a supplement composed of tocopherols and rich in γ-tocopherol and ascorbic acid is effective in restoring fertility in cases where oxidative stress and high levels of tyrosine nitration are associated with male infertility.

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In vivo respiratory toxicology of cooking oil fumes: Evidence, mechanisms and prevention

Yongsheng Ma, Linjing Deng, Ping Ma, Yang Wu, Xu Yang, Fang Xiao, Qihong Deng

J Hazard Mater . 2020 Jul 12;402:123455. doi: 10.1016/j.jhazmat.2020.123455. Online ahead of print.


Background: As cooking is an essential part of people’s daily life, cooking oil fumes (COF) has been recognized as one of the major indoor air pollutant. Mounting epidemiological evidence has indicated that COF exposure is significantly associated with an increased risk of various health effects including lung cancer, but toxicological studies are very limited.

Objectives: We conduct a systematic study to provide toxicological evidence of COF exposure on the lungs, to examine the underlying toxicological mechanism, and to suggest intervention measures to mitigate this toxicity.

Methods: A total 96 female rats were randomly divided into control groups, COF exposure groups (0.2, 2, 20 mg/kg) and vitamin E protection groups, receiving appropriate treatment for 30 days. First we measured airway hyperresponsiveness (AHR) followed by a lung histological analysis to investigate the toxicological effects of COF. We next analyzed the biomarkers of oxidative stress, inflammation, and apoptosis to examine the underlying toxicological mechanism, and finally we investigated the protective effects of vitamin E against the toxicity of COF.

Results: AHR measurement indicated that the airway resistance increased with the COF dose and the lung histological assay showed narrowing of the airway lumen, which provided evidence of the toxicological effects of COF. The biomarkers of oxidative stress (ROS and MDA), pro-inflammation (TNF-α and IL-1β), and apoptosis (NF-κB and Caspase-3) were all significantly increased with COF dose. We observed that above toxicological effects and biomarker levels induced by COF were significantly ameliorated after administration of VE.

Conclusion: The toxicity of cooking oil fumes on the lungs is clear from the evidence and mechanism, and can be ameliorated by vitamin E. We suggested that oxidative stress may be primarily responsible for the observed cooking oil fumes-induced toxicity.

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A Novel Vitamin E TPGS-Based Formulation Enhances Chlorhexidine Bioavailability in Corneal Layers

Ciro Caruso, Amalia Porta, Alessandra Tosco, Daniela Eletto, Luigi Pacente, Silvia Bartollino, Ciro Costagliola

Pharmaceutics . 2020 Jul 8;12(7):E642. doi: 10.3390/pharmaceutics12070642.


Keratitis is a severe condition characterized by inflammation of the cornea following a local trauma. The most common ocular disease is the bacterial one, which requires an antibiotic treatment. The major limitation of this therapy is the resistance of the antibiotic. For this reason, alternative procedures have been developed and consist of antimicrobial molecules. One of the most used is the chlorhexidine gluconate, which has shown activity versus Gram-positive and Gram-negative bacteria and fungi. In addition to its efficiency, chlorhexidine shows low toxicity levels for mammalian cells and is a low-cost molecule. Despite its multiple benefits, chlorhexidine, if used at concentrations higher than 0.02% (w/w), can cause local eye irritation. Additionally, its poor penetrability through the cornea makes necessary frequent instillation of eye drops for a prolonged time. Due to these limitations, alternative drug delivery strategies are required. Here, we report a novel formulation based on the combination of d-alpha-tocopherol polyethylene glycol 1000 succinate with chlorhexidine, which results in higher accumulation of the drug in human corneas measured by liquid chromatography and strong antimicrobial activity. Moreover, this formulation does not cause any toxic effect on human cells and is well tolerated by rabbit eyes. Therefore this novel formulation represents a good candidate for the treatment of keratitis that overcomes the risk of antibiotic resistance.

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Effect of Zinc, Selenium, and Vitamin E Administration on Semen Quality and Fertility of Male Dromedary Camels with Impotentia Generandi

Ahmed Ali, Derar R Derar, Tamim M Alhassun, Tariq I Almundarij

Biol Trace Elem Res . 2020 Jul 6. doi: 10.1007/s12011-020-02276-8. Online ahead of print.


This study aimed to investigate the effect of zinc (Zn), selenium (Se), and vitamin E (Vit E) administration on semen quality and fertility in male dromedary camels with impotentia generandi (IG, post-coital infertility). Factors that may affect response to treatment were investigated. Thirty-three IG-affected and five fertile camels were included. Case history was obtained, and breeding sound examination was performed. Semen was collected using electroejaculation. IG-camels were classified according to initial sperm count, body condition score, age, duration of infertility, IG-type, and testicular size. IG-camels were treated with a combination of intramuscular injections of Vit E (α-tocopherol acetate, 1 mg/kg bw) and Se (sodium selenite, 0.088 mg/kg bw) once every week for three successive weeks and by daily oral administration of 360 mg of zinc gluconate for 5 successive weeks. Semen quality was estimated before and after treatment. IG-treated camels were allowed to mate females in estrus, and conception rates were calculated. The results showed that sperm cell concentration, sperm motility, and viability significantly increased, while sperm abnormality significantly decreased after treatment (P < 0.01). Positive correlations were observed between initial sperm cell count and post-treated sperm count (P = 0.001), sperm motility (P = 0.01), and viability (P = 0.002). Other variables and their interactions did not affect response to treatment. Conception rates improved after treatment. In conclusion, Zn, Se, and Vit E administration improved semen quality and fertility in male dromedary camels with impotentia generandi. Initial sperm count can be used to predict the degree of camel response to treatment.

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Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial

Mohammad Taghi Beigmohammadi, Sama Bitarafan, Azin Hoseindokht, Alireza Abdollahi, Laya Amoozadeh, Maedeh Mahmoodi Ali Abadi, Morteza Foroumandi

Trials . 2020 Jul 6;21(1):614. doi: 10.1186/s13063-020-04547-0.


Objectives: This study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19.

Trial design: This study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial.

Participants: We are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran. The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities. The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month.

Intervention and comparator: Duration of intervention: 7 days from randomization Intervention in the treatment group: Vitamin A 25,000 IU daily Vitamin D 600,000 IU once during study Vitamin E 300 IU twice daily Vitamin C is taken four times per day B vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg] The control group will not receive any supplements or placebo. All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand).

Main outcomes: 1. Weight, height, and BMI 2. Severity of pulmonary involvement according to CT scan 3. Respiratory support (invasive or non-invasive) 4. Percentage of oxygen saturation (SpO2 level) 5. Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-α 6. The patient’s body temperature 7. The presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys) 8. Duration of hospitalization 9. Mortality rate RANDOMIZATION: At baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients.

Blinding (masking): Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group.

Numbers to be randomized (sample size): The researchers plan to include 60 patients in total, with 30 patients in each group.

Trial status: This is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020.

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Administration of Vitamin D 3 and E supplements reduces neuronal loss‏ and oxidative stress in a model of rats with Alzheimer’s disease

Shima Mehrabadi, Seyed Shahabeddin Sadr

Neurol Res . 2020 Jul 4;1-7. doi: 10.1080/01616412.2020.1787624. Online ahead of print.


Alzheimer’s disease (AD) is the most common neurodegenerative disease across the world. The major cause of AD is extensive oxidative stress and inflammation in central nervous system (CNS). Vitamin D3 and E are the most known vitamins that control oxidative stress and mitochondrial respiratory function. They may prevent neuronal loss in AD. Few studies have been conducted to assess the effect of vitamins on AD. Therefore, the aim of this study was to assess the effect of vitamin D3 and E on AD. Methods: In this study, 60 rats were randomly divided into six groups (n = 10) namely the control group, sham group, AD group with intra-hippocampal Aβ1-40 injection, AD+vitamin D3 group, AD+vitamin E group and AD+vitamin D3 and E group. Memory and learning were measured by the Novel Object Recognition (NOR) test. Neuronal survival was assessed by H&E and cresyl violet staining, and oxidative stress was measured by malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. In vitamin-treated groups, learning and memory, which were measured by NOR, improved significantly. Vitamin D3 and E administration decreased neuronal loss in AD brain rats. Results: Results showed that MDA decreased and SOD increased in treatment groups; but, a combination of vitamin D3 and E was more effective in decreasing oxidative stress in AD compared to other treatment groups. Conclusion: The present study indicated that vitamin D3 and E and their combination can improve memory and learning deficit, and decrease neuronal loss and oxidative stress in Alzheimer’s model.

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Vitamin E promotes ovine Sertoli cell proliferation by regulation of genes associated with cell division and the cell cycle

Yuefeng Gao, Wei Lu, Luyang Jian, Zoltan Machaty, Hailing Luo

Anim Biotechnol . 2020 Jul 2;1-9. doi: 10.1080/10495398.2020.1788044. Online ahead of print.


The effect of Vitamin E on the proliferation of ovine Sertoli cells was investigated. Sertoli cells were isolated and treated with various amounts of Vitamin E (0 μM, 400 μM, 800 μM, 1000 μM, 1200 μM, 1400 μM and 1600 μM) for 24 h. We found that at the concentration of 1200 μM, Vitamin E promoted Sertoli cell proliferation very effectively. It also increased the proportion of cells in the G1 phase while reduced that in the S and G2/M phases, suggesting that its effect on Sertoli cell proliferation is achieved by enhancing progression through the cell cycle. In addition, Vitamin E significantly up-regulated the transcript level of the PDPN, BMP6, AMPKα, GSK3β, Myc, and CDK6 genes and down-regulated that of PPARγ, Cyclin B1 and CDK4 as determined by qRT-PCR. Western blot analysis revealed that the expression of BMP6 and PDPN was also upregulated at the protein level, in accordance with the results of the qRT-PCR. Taken together, Vitamin E promoted Sertoli cell proliferation by affecting the expression of genes that regulate cell division and the cell cycle; this indicates that it can have a positive effect on sheep reproductive performance.

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Infant Rhesus Macaque Brain α-Tocopherol Stereoisomer Profile Is Differentially Impacted by the Source of α-Tocopherol in Infant Formula

Matthew J Kuchan, Katherine M Ranard, Priyankar Dey, Sookyoung Jeon, Geoff Y Sasaki, Karen J Schimpf, Richard S Bruno, Martha Neuringer, John W Erdman

J Nutr . 2020 Jul 2;nxaa174. doi: 10.1093/jn/nxaa174. Online ahead of print.


Background: α-Tocopherol (αT) in its natural form [2’R, 4’R, 8’R αT (RRR-αT)] is more bioactive than synthetic α-tocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown.

Objective: We sought to compare αT and stereoisomer status in infant rhesus macaques (Macaca mulatta) fed infant formula (RRR-αT or all rac-αT) with a reference group fed a mixed diet of breast milk and maternal diet.

Methods: From 1 d after birth until 6 mo of age, infants (n = 23) were either nursery reared and exclusively fed 1 of 2 formulas by staff personnel or were community housed with their mothers and consumed a mixed reference diet of breast milk (69 mL/d at 6 mo) transitioning to monkey diet at ∼2 mo (MF; n = 8). Formulas contained either 21 μmol RRR-αT/L (NAT-F; n = 8) or 30 μmol all rac-αT/L (SYN-F; n = 7). Total αT and αT stereoisomers were analyzed in breast milk at 2, 4, and 6 mo and in monkey plasma and liver and 6 brain regions at 6 mo of age. α-Tocopherol transfer protein (α-TTP), lipoprotein αT, and urinary α-carboxyethyl-hydroxychroman (α-CEHC) were measured. One-way ANOVA with Tukey’s post-hoc test was used for analysis.

Results: At study termination, plasma, liver, lipoprotein, and brain total αT did not differ between groups. However, the NAT-F-fed group had higher RRR-αT than the SYN-F-fed group (P < 0.01) and the MF group (P < 0.0001) in plasma (1.7- and 2.7-fold) and brain (1.5- and 2.5-fold). Synthetic αT 2R stereoisomers (SYNTH-2R) were generally 3- and 7-fold lower in brain regions of the NAT-F group compared with those of the SYN-F and MF groups (P < 0.05). SYNTH-2R stereoisomers were 2-fold higher in MF than SYN-F (P < 0.0001). The plasma percentage of SYNTH-2R was negatively correlated with the brain percentage of RRR-αT (r = -0.99, P < 0.0001). Brain αT profiles were not explained by α-TTP mRNA or protein expression. Urine α-CEHC was 3 times higher in the NAT-F than in the MF group (P < 0.01).

Conclusions: Consumption of infant formulas with natural (NAT-F) compared with synthetic (SYN-F) αT differentially impacted brain αT stereoisomer profiles in infant rhesus macaques. Future studies should assess the functional implications of αT stereoisomer profiles on brain health.

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Inflammatory Diseases and Vitamin E – What Do We Know and Where Do We Go?

Maria Wallert, Lisa Börmel, Stefan Lorkowski

Mol Nutr Food Res . 2020 Jul 21;e2000097. doi: 10.1002/mnfr.202000097. Online ahead of print.


Inflammation-driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, was identified as a key player in inflammation and the development of various inflammation-mediated disorders, with nucleotide-binding domain and leucine-rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here we provide an overview about the cellular signaling pathways underlying nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells (NF-κB)- and NLRP3-mediated inflammatory processes, the pathogenesis of the inflammatory diseases atherosclerosis and non-alcoholic fatty liver disease (NAFLD); next, we discuss the current state of knowledge for drug-based and dietary-based interventions for treating cardiovascular diseases and NAFLD. To date one of the most important antioxidant in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti-inflammatory activity. Recent publications suggest that vitamin E – and possibly metabolites of vitamin E – are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.

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