Clinical Efficacy of Topical CoQ10 and Vitamin-E Eye-drop in Retinopathy of Prematurity

Akdogan M, Polat O

Med Hypothesis Discov Innov Ophthalmol. 2019 Winter;8(4):291-297.


Treatment strategy for retinopathy of prematurity (ROP) includes anti-vascular endothelial growth factor (anti-VEGF) and/or laser therapy. The aim of this study was to investigate the clinical effects of topical Coqun® eye drop (CoQ10 and Vitamin-E) on the progression and treatment of ROP. One hundred and ten infants with type 1 ROP who received Coqun® (Coqun group) and 131 infants with type 1 ROP who did not receive Coqun® (control group) were included in this retrospective analysis. All patients were follow-up until retinal vascular maturation was complete. Intravitreal bevacizumab (IVB) injection or laser photocoagulation (LPC) were apply if needed. Treatment frequency, treatment response and mean follow-up time were compare. The number of IVB was similar between the groups, but infants in the Coqun group underwent significantly fewer LPC procedure than those in the control group (P = 0.022). The mean follow-up time was significantly shorter in infants receiving Coqun® in stage 1 ROP (P = 0.017) and similar in stages 2-4 ROP and aggressive posterior retinopathy of prematurity (APROP). The number of LPC procedure was fewer in the Coqun group in APROP (P = 0.043). These results indicate that faster retinal vascular maturation in infants with low-grade ROP and lower number of treatments with APROP could be achieve with Coqun® therapy.

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Advancing the Role of Gamma-Tocotrienol as Proteasomes Inhibitor: A Quantitative Proteomic Analysis of MDA-MB-231 Human Breast Cancer Cells

Ramdas P, Radhakrishnan AK, Abdu Sani AA, Kumari M, Anandha Rao JS, Abdul-Rahman PS

Biomolecules. 2019 Dec 21;10(1). pii: E19. doi: 10.3390/biom10010019.


Tocotrienol, an analogue of vitamin E has been known for its numerous health benefits and anti-cancer effects. Of the four isoforms of tocotrienols, gamma-tocotrienol (γT3) has been frequently reported for their superior anti-tumorigenic activity in both in vitro and in vivo studies, when compared to its counterparts. In this study, the effect of γT3 treatment in the cytoplasmic and nuclear fraction of MDA-MB-231 human breast cancer cells were assessed using the label-free quantitative proteomics analysis. The cytoplasmic proteome results revealed the ability of γT3 to inhibit a group of proteasome proteins such as PSMA, PSMB, PSMD, and PSME. The inhibition of proteasome proteins is known to induce apoptosis in cancer cells. As such, the findings from this study suggest γT3 as a potential proteasome inhibitor that can overcome deficiencies in growth-inhibitory or pro-apoptotic molecules in breast cancer cells. The nuclear proteome results revealed the involvement of important nuclear protein complexes which hardwire the anti-tumorigenesis mechanism in breast cancer following γT3 treatment. In conclusion, this study uncovered the advancing roles of γT3 as potential proteasomes inhibitor that can be used for the treatment of breast cancer.

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Chemoprotective and antiobesity effects of tocols from seed oil of Maqui-berry: Their antioxidative and digestive enzyme inhibition potential

Bastías-Montes JM, Monterrosa K, Muñoz-Fariña O, García O, Acuña-Nelson SM, Vidal-San Martín, Quevedo-Leon R, Kubo I, Avila-Acevedo JG, Domiguez-Lopez M, Wei ZJ, Thakur K, Cespedes-Acuña CL

Food Chem Toxicol. 2019 Dec 17:111036. doi: 10.1016/j.fct.2019.111036.


Maqui-berry (Aristotelia chilensis) is the emerging Chilean superfruit with high nutraceutical value. Until now, the research on this commodity was focused on the formulations enriched with polyphenols from the pulp. Herein, contents of tocols were compared in the seed oil of Maqui-berry obtained through three different extraction methods followed by determining their antioxidative and enzyme inhibitions in-vitro. Firstly, oilseed was extracted with n-hexane (Soxhlet method), chloroform/methanol/water (Bligh and Dyer method) and pressing (industrial). These samples were used to access their effects against DPPH, HORAC, ORAC, FRAP, Lipid-peroxidation (TBARS), α-amylase, α-glucosidase, and pancreatic lipase. All the isomers of tocopherol and tocotrienol were identified, and β-sitosterol was the only sterol found in higher amounts than other vegetable oils. The Bligh and Dyer method could lead to the highest antioxidative capacity compared to Soxhlet and press methods likely because the latter have a higher amount of tocopherols. Further, seed oil from Maqui berry and their tocols (α, β, γ, δ-tocopherols, tocotrienols, and β-sitosterol) warrant clinical investigation for their antioxidative and antiobesity potential. Taken together, these findings provide relevant and suitable conditions for the industrial processing of Maqui-berry.

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Nutritional Neuropathies

Gwathmey KG, Grogan J

Muscle Nerve. 2019 Dec 14. doi: 10.1002/mus.26783.


Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Though these neuropathies assume different patterns, most are length-dependent, sensory axonopathies. Cobalamin deficiency neuropathy is the exception, often presenting with a non-length-dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome. In contrast to those nutrients for which deficiencies produce neuropathies, pyridoxine toxicity results in a non-length-dependent sensory neuronopathy. Deficiencies occur in the context of malnutrition, malabsorption, increased nutrient loss (such as with dialysis), autoimmune conditions such as pernicious anemia, and with certain drugs that inhibit nutrient absorption. When promptly identified, therapeutic nutrient supplementation may result in stabilization or improvement of these neuropathies.

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Evaluation of oxidative stress in caprine anaplasmosis and effect of vitamin E-selenium in monitoring oxidative stress

Dhanasree G, Pillai UN, Deepa C, Ambily VR, Shynu M, Sunanda C

Trop Anim Health Prod. 2019 Dec 14. doi: 10.1007/s11250-019-02175-8.


Caprine anaplasmosis is an economically important tick-borne rickettsial disease that affects goats all over the world. Microscopic examination of stained blood smears from 162 animals revealed inclusion bodies of Anaplasma spp. in 24 cases. Genus specific PCR for Anaplasma spp. yielded positive results in 22 cases. All the diseased animals showed a significant fall in the mean values of antioxidants such as reduced glutathione, superoxide dismutase and catalase and a significant increase in the level of lipid peroxidation. Out of the 22 animals positive for anaplasmosis both in blood smear and PCR, 16 female non pregnant goats selected for study were divided into two groups consisting of eight animals each. Animals belonging to groups I and II were treated with oxytetracycline dihydrate. In addition, animals of group II were supplemented with vitamin E-selenium combination. Oxidative stress parameters were rechecked on the 10th day of treatment. At the end of the study period, a significant reduction in malondialdehyde level and a significant increase in mean value of superoxide dismutase were detected in group II. While there was a significant reduction in lipid peroxidation and a significant increase in superoxide dismutase and catalase values within both the groups after treatment, reduced glutathione showed no significant difference within the group.

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Vitamin E sequestration by liver fat in humans

Violet PC, Ebenuwa IC, Wang Y, Niyyati M, Padayatty SJ, Head B, Wilkins K, Chung S, Thakur V, Ulatowski L, Atkinson J, Ghelfi M, Smith S, Tu H, Bobe G, Liu CY, Herion DW, Shamburek RD, Manor D, Traber MG, Levine M.

JCI Insight. 2019 Dec 10. pii: 133309. doi: 10.1172/jci.insight.133309.


BACKGROUND We hypothesized that obesity-associated hepato-steatosis served as a pathophysiologic chemical depot for fat-soluble vitamins and altered normal physiology. Using α-tocopherol (vitamin E) as a model vitamin, pharmacokinetics and kinetics principles were utilized to determine whether excess liver fat sequestered α-tocopherol in women with obesity-associated hepato-steatosis vs healthy controls.METHODS Custom-synthesized deuterated α-tocopherols (d3- and d6-α-tocopherols) were administered to hospitalized healthy women and women with hepato-steatosis under IND guidelines. Serial samples obtained over 72 hours were analyzed by LC/MS. Fluorescent-labelled α-tocopherol was custom-synthesized for cell studies.RESULTS In healthy subjects, 85% of intravenous d6-α-tocopherol disappeared from the circulation within 20 minutes but reappeared within minutes and peaked at 6-8 hours. d3- and d6-α-Tocopherols localized to lipoproteins. Lipoprotein redistribution occurred only in vivo within 1h, indicating a key role of liver in rapid uptake and re-release into the circulation. Compared to healthy subjects, subjects with hepato-steatosis had similar d6-α-tocopherol entry rates into liver, but reduced initial release rates (p<0.001). Similarly, pharmacokinetics parameters of AUC and Maximum Concentration (Cmax) were reduced (AUC0-8 ,p<0.01;Cmax p<0.02) in hepato-steatosis subjects, indicating reduced hepatic d6-α-tocopherol output. Reduced kinetics and pharmacokinetics parameters (AUC and Cmax) in hepato-steatosis subjects who received 2 mg were mirrored by similar reductions in healthy subjects when comparing 5 and 2 mg doses. In vitro, fluorescent-labelled α-tocopherol localized specifically to lipid in fat-loaded hepatocytes, indicating sequestration.CONCLUSIONS The unique role of the liver in vitamin E physiology is dysregulated by excess liver fat. Obesity-associated hepato-steatosis may produce unrecognized hepatic vitamin E sequestration, which might subsequently drive liver disease. Our findings raise the possibility that hepato-steatosis may similarly alter hepatic physiology of other fat-soluble vitamins.

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Alpha-Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring

Cabral EV, Vieira LD, Sant'Helena BRM, Ribeiro VS, Farias JS, Aires RS, Paz ST, Muzi-Filho H, Paixão AD, Vieyra A

Clin Exp Pharmacol Physiol. 2019 Dec;46(12):1151-1165. doi: 10.1111/1440-1681.13161.


Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 mol/L NaCl for 20 days before and during pregnancy. α-Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post-weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca2+ -ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α-Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of CrCl , which was sensitized for a sharp decrease after α-Tocopherol. In conclusion, the combination of maternal saline overload and high α-Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome.

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Effects of pentoxifylline and tocopherol on a rat-irradiated jaw model using micro-CT cortical bone analysis

Nguyen TTH, Eo MY, Seo MH, Myoung H, Kim SM, Lee JH

Eur Arch Otorhinolaryngol. 2019 Dec;276(12):3443-3452. doi: 10.1007/s00405-019-05600-8.



A combination of pentoxifylline (PTX) and tocopherol (TP) is believed to reduce chronic fibrosis and induce bone healing in osteoradionecrosis (ORN) of the mandible, but evidence of its therapeutic effectiveness for cortical bone is lacking. This study was designed to determine the effect of combined PTX and TP (PTX + TP) on mandibular cortical bone remodeling in a rat model of ORN, using micro-CT and histological analysis.


Forty-eight 8-week-old male Sprague-Dawley rats were randomly divided into irradiated (n = 40) and non-irradiated (n = 8) groups. Animals in the irradiated group were divided into four sub-groups, including PTX, TP, PTX + TP, and normal saline. Three weeks after irradiation, mandibular posterior tooth extraction was performed, and animals were sacrificed 7 weeks after irradiation. The mandibles were analyzed using micro-CT and histological evaluation.


The alveolar bone height, cortical bone thickness, cortical bone volume, and total cortical bone surface of the PTX + TP group were significantly greater than those of other irradiated groups (p < 0.05). In 3D reconstructed images, the residual volumes of cortical and cancellous bone were inadequate in the irradiated groups.


We found that a combination of PTX and TP improved quality and quantity of cortical bone in irradiated rat mandibles, thus providing supporting evidence of its utility as a treatment and prophylactic agent in ORN. We observed inadequate volumes of cortical and cancellous bone in ORN mandibles, suggesting that cortical bone could play an important role in further ORN studies.

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Novel Antioxidative Activity of Astaxanthin and Its Synergistic Effect with Vitamin E

Kogure K

J Nutr Sci Vitaminol (Tokyo). 2019;65(Supplement):S109-S112. doi: 10.3177/jnsv.65.S109.


Astaxanthin (Asx) is known to be a potent quencher of singlet oxygen and an efficient scavenger of superoxide anion. However, the scavenging activity of Asx toward the hydroxyl radical was currently unclear because the high lipophilicity of Asx prevents analysis of such activity in water. Liposomes containing Asx (Asx-lipo) were previously shown to be dispersed in water. Analysis of the hydroxyl radical scavenging activity of Asx-lipo demonstrated a dose-dependence in water, with the effect of Asx being more potent than the vitamin E α-tocopherol (α-T). Furthermore, liposomes co-encapsulating Asx and vitamin E derivatives, namely tocotrienols (T3), showed a synergistic elimination effect on singlet oxygen and hydroxyl radical, although the antioxidative activity of liposomes co-encapsulating Asx and α-T was lower than the calculated additive value of each independent activity. A calculation of the most stable structure of Asx in the presence of α-T or T3, suggested that only T3 was able to hydrogen bond with Asx, and the Asx polyene chain partially interacting with the α-T3 triene chain, which could explain the synergistic effect between Asx and T3, but not Asx and α-T. This review introduces the hydroxyl radical scavenging activity of Asx, and its synergistic effect with T3.

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Preventive Effect of Polyunsaturated Fatty Acid and Vitamin E in Rice Bran Oil on Lifestyle-Related Diseases

Fujiwara Y

J Nutr Sci Vitaminol (Tokyo). 2019;65(Supplement):S34-S37. doi: 10.3177/jnsv.65.S34.


The dietary fat intake of Japanese is thought to be more appropriate than in Western countries; however there is a range of differences of individuals in the amounts of fat intake and n-6/n-3 ratio. Therefore, it is important what kind of vegetable oils are used for cooking in order to consider the total balance of fat intake. Rice bran oil (RBO) is expected to reduce plasma cholesterol and be useful for prevention of cardiovascular disease because it contains several effective ingredients. RBO is rich in linoleic and oleic acid. RBO contains γ-oryzanol, which is well known to reduce plasma cholesterol levels. Furthermore, it contains tocotrienols, which are analogs of vitamin E, reported to have unique bioactivity different from that of α-tocopherol. The biological function of these components and their potential to prevent Japanese lifestyle-related diseases are discussed.

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