Corneal UV Protective Effects of a Topical Antioxidant Formulation: A Pilot Study on In Vivo Rabbits

Marisa Palazzo, Francesco Vizzarri, Lubomir Ondruška, Michele Rinaldi, Luigi Pacente, Germano Guerra, Francesco Merolla, Ciro Caruso, Ciro Costagliola

Int J Mol Sci . 2020 Jul 30;21(15):E5426. doi: 10.3390/ijms21155426.

Abstract

This study aimed to evaluate the protective effect of a topical antioxidant and ultraviolet (UV) shielding action formulation containing riboflavin and D-α-tocopherol polyethylene glycol succinate (TPGS) vitamin E against corneal UV-induced damage in vivo rabbit eyes. In vivo experiments were performed using male albino rabbits, which were divided into four groups. The control group (CG) did not receive any UV irradiation; the first group (IG) was irradiated with a UV-B-UV-A lamp for 30 min; the second (G30) and third (G60) groups received UV irradiation for 30 and 60 min, respectively, and were topically treated with one drop of the antioxidant and shielding formulation every 15 min, starting one hour before irradiation, until the end of UV exposure. The cornea of the IG group showed irregular thickening, detachment of residual fragments of the Descemet membrane, stromal fluid swelling with consequent collagen fiber disorganization and disruption, and inflammation. The cornea of the G30 group showed edema, a mild thickening of the Descemet membrane without fibrillar collagen disruption and focal discoloration, or inflammation. In the G60 group, the cornea showed a more severe thickening, a more abundant fluid accumulation underneath the Descemet membrane with focal detachment, and no signs of severe tissue alterations, as were recorded in the IG group. Our results demonstrate that topical application of eye drops containing riboflavin and TPGS vitamin E counteracts UV corneal injury in exposed rabbits.

Fabrizio Fontana, Michela Raimondi, Monica Marzagalli, Matteo Audano, Giangiacomo Beretta, Patrizia Procacci, Patrizia Sartori, Nico Mitro, Patrizia Limonta

Free Radic Biol Med . 2020 Jul 29;S0891-5849(20)31145-X. doi: 10.1016/j.freeradbiomed.2020.07.009. Online ahead of print.

Abstract

The therapeutic options for castration resistance prostate cancer (CRPC) are still limited. Natural bioactive compounds were shown to possess pro-death properties in different tumors. We previously reported that δ-tocotrienol (δ-TT) induces apoptosis, paraptosis and autophagy in CRPC cells. Here, we investigated whether δ-TT might exert its activity by impairing mitochondrial functions. We demonstrated that, in PC3 and DU145 cells, δ-TT impairs mitochondrial respiration and structural dynamics. In both cell lines, δ-TT triggers mitochondrial Ca²⁺ and ROS overload. In PC3 cells, both Ca²⁺ and ROS mediate the δ-TT-related anticancer activities (decrease of cell viability, apoptosis, paraptosis, autophagy and mitophagy). As expected, in autophagy-defective DU145 cells, Ca²⁺ overload was involved in δ-TT-induced pro-death effects but not in autophagy and mitophagy. In this cell line, we also demonstrated that ROS overload is not involved in the anticancer activities of δ-TT, supporting a low susceptibility of these cells to ROS-related oxidative stress. Taken together, these data demonstrate that, in CRPC cells, δ-TT triggers cell death by inducing mitochondrial functional and structural impairments, providing novel mechanistic insights in its antitumor activity.

Bruna C Agustinho, Lucia M Zeoula, Nadine W Santos, Erica Machado, Emerson H Yoshimura, Jessyca C R Ribas, Janaina M Bragatto, Mariana R Stemposki, Vanessa J Dos Santos, Antonio P Faciola

Animals (Basel) . 2020 Jul 29;10(8):E1294. doi: 10.3390/ani10081294.

Abstract

This study aimed to evaluate the effects of the supplementation of flaxseed oil and/or vitamin E on dry matter (DM) and nutrient digestibility, milk composition, fatty acid composition, and antioxidant capacity in buffalo milk. Four crossbred female dairy water buffaloes (97 ± 22 days in milk; 6.57 ± 2.2 kg of milk/day, mean ± SD) were distributed in a 4 × 4 Latin square design, with a 2 × 2 factorial arrangement (with or without flaxseed oil at 25 g/kg dry matter; with or without vitamin E at 375 IU/kg dry matter). The experimental period was divided into four periods of 21 days each (16 days for adaptation; five days for data collection). There were four treatments: control diet (no flaxseed oil and no added vitamin E); flaxseed oil diet (flaxseed oil at 25 g/kg DM); vitamin E diet (vitamin E at 375 IU/kg DM), and a combination of both flaxseed oil and vitamin E. The animals were fed total mixed ratios. For all response variables, there was no interaction between flaxseed oil and vitamin E. Flaxseed oil supplementation reduced neutral detergent fiber (NDF) and acid detergent fiber (ADF) apparent total tract digestibility, increased the n-3 fatty acid concentration in milk approximately three-fold while reducing the n-6/n-3 ratio from 9.3:1 to 2.4:1. Vitamin E supplementation increased NDF apparent total tract digestibility and milk total antioxidant capacity. Although there was no interaction between the treatments; flaxseed oil supplementation in lactating buffaloes increased polyunsaturated fatty acid, while vitamin E supplementation increased antioxidant capacity and decreased oxidation products.

Enitome E Bafor, Adaeze P Uchendu, Omorede E Osayande, Osemelomen Omoruyi, Uyi G Omogiade, Evuarherhere E Panama, Olusola O Elekofehinti, Ebube L Oragwuncha, Asanat Momodu

Reprod Sci . 2020 Jul 28. doi: 10.1007/s43032-020-00273-9. Online ahead of print.

Abstract

Polycystic ovary syndrome (PCOS) affects up to 10% of women within reproductive ages and has been a cause of infertility and poor quality of life. Alteration in the oxidant-antioxidant profile occurs in PCOS. This study, therefore, investigates the contribution of ascorbic acid (AA) and alpha-tocopherol(ATE) on different PCOS parameters. The mifepristone and letrozole models were used, and young mature female mice were randomly assigned to groups of six per group. On PCOS induction with either mifepristone or letrozole, mice were administered AA and ATE at doses ranging from 10-1000mg/kg to 0.1-1000 mg/kg in the respective models. Vaginal cytology, body weights, and temperature, as well as blood glucose, testosterone, and insulin levels, were measured. Total antioxidant capacity and malondialdehyde levels were analyzed. Determination of gene expression of some reactive oxygen species and histomorphological analysis on the ovaries and uteri were performed. At the end of the experiments, AA and ATE restored reproductive cycling, with AA being more effective. AA and ATE increased fasting blood glucose but had no significant effect on serum insulin levels. AA decreased testosterone levels, but ATE caused slight increases. AA and ATE both increased total antioxidant capacity and decreased malondialdehyde levels. AA and ATE also slightly upregulated the mRNA expressions of catalase, superoxide dismutase, and heme oxygenase 1 mainly. AA and ATE also decreased ovarian weight and mostly resolved cysts in the ovaries and congestion in the uterus. This study has shown that AA and ATE are beneficial in the therapy of PCOS.

Nahid Lorzadeh, Yasaman Kazemirad, Nastran Kazemirad

J Perinat Med . 2020 Jul 28;48(6):625-629. doi: 10.1515/jpm-2019-0469.

Abstract

Objectives Preeclampsia is a hypertensive disorder associated with pregnancy and is the leading cause of both maternal and neonatal morbidity and mortality. Recent reports suggest that free radical-induced endothelial cell injury might be an etiologic factor in the pathogenesis of preeclampsia. The aim of this study was to determine the protective effects of vitamins C and E for the prevention of preeclampsia. Methods This clinical trial was conducted in the year 2018 in the clinical centers of Lorestan University of Medical Sciences. One hundred and sixty nulliparous women aged 18-38 years without any risk factors for preeclampsia were divided into two groups. The first group received a 400-IU/day dose of vitamin E orally and a 1000-mg/day dose of vitamin C with iron tablets during 20-24 weeks of pregnancy, while the control group received only iron tablets. Finally, the data were analyzed using descriptive statistics and frequency distribution tables. Results The incidence of preeclampsia in the control group was 17.5% and in the intervention group was 5%, which was significantly different. The mean systolic pressures before and after intervention were 99.43 ± 7.8 and 12.44 ± 19.1, respectively, in the control group, and 99.3 ± 8.3 and 106.12 ± 13.25, respectively, in the intervention group (P < 0.001). The mean diastolic pressures before and after intervention in the control group were 62.7 ± 13.6 and 62.7 ± 4.7 (P < 0.001), respectively. Conclusion The results of this study show that vitamins C and E have protective effects against preeclampsia by alleviating the overall blood pressure.

Benjamin D Lovin, Jonathan S Choi, Nathan R Lindquist, Jack Phan, Paul W Gidley, Marc-Elie Nader

Otol Neurotol . 2020 Jul 27. doi: 10.1097/MAO.0000000000002781. Online ahead of print.

Abstract

Objective: Temporal bone osteoradionecrosis (TBORN) is a rare, chronic complication of head and neck radiation. Initial treatment consists of conservative management, with surgical resection of necrotic bone indicated for cases of severe, symptomatic, or progressive disease. Pentoxifylline-tocopherol (PENTO) has demonstrated usefulness for osteoradionecrosis of other head and neck subsites. Herein, we report five TBORN cases utilizing this protocol.

Study design: Retrospective case series.

Setting: Tertiary referral center.

Patients: This case series describes five TBORN cases in which the PENTO protocol was used in conjunction with conservative management. All patients were women and average age was 61 ± 8 years.

Intervention: All patients received a daily dose of 800 mg of pentoxifylline and 1 g of tocopherol. Four of the five patients received systemic and/or ototopical antibiotics as an antimicrobial regimen before and/or during the PENTO protocol.

Main outcome measures: Details regarding the total duration of protocol, improvement in symptoms, exposed bone and radiographic changes, and duration until first improvement of exposed bone were collected retrospectively.

Results: The average duration of PENTO protocol was 302 ± 166 days. Four of the five (80%) patients demonstrated a decrease in exposed ear canal bone. Three of the five (60%) patients had stable or improvement in otologic symptoms of TBORN. One patient progressed to diffuse TBORN. The average duration until first improvement in exposed bone was 193 ± 137 days.

Conclusions: The PENTO protocol may be a useful adjunct to conservative measures in the management of localized TBORN. We recommend trialing the protocol for at least 12 months.

Gitanjali Gautam, Raj Kumar Duary, Kuldeep Gupta, Charu Lata Mahanta

Int J Biol Macromol . 2020 Jul 26;164:1328-1341. doi: 10.1016/j.ijbiomac.2020.07.196. Online ahead of print.

Abstract

Tocotrienols (T3) are vitamin E components that inhibit 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), a primary target for cholesterol management. T3 was extracted from rice bran (RBE) using ultrasonic energy keeping solute: solvent ratio, power and time on specific energy and T3 concentration as responses as per Box-Behnken Design. The lowest specific energy (52.38 ± 0.14 J mL^-1) uptake by the sample was most effective in enhancing the concentration of T3 in RBE (199.34 ± 0.63 μg mL^-1). In vitro HMGR kinetics and in silico binding interactions of the identified α-, δ- and γ-T3 fractions were studied. Enzyme kinetic studies revealed an uncompetitive mode of inhibition by α-T3, γ-T3, and RBE and a mixed mode of inhibition for δ-T3. γ-T3 showed lowest IC₅₀ concentration (11.33 μg mL^-1) followed by α-T3 (16.73 μg mL^-1), RBE (20.45 μg mL^-1) and δ-T3 (23.16 μg mL^-1). Molecular docking studies highlighted the hydrogen bonding of δ-T3 with Gln766 and α- and γ-T3 with Met655 and Val805 amino acid residues at the NADPH binding site of HMGR. Results indicate the potential use of T3 enriched RBE optimally extracted using ultrasound as potent HMGR inhibitor.

Francisca A de Leeuw, William G Honer, Julie A Schneider, Martha Clare Morris

J Alzheimers Dis . 2020 Jul 25. doi: 10.3233/JAD-200166. Online ahead of print.

Abstract

Background: Higher vitamin E intake has been widely related to lower risks of cognitive decline and dementia. Animal models suggest that this relationship might be (partially) explained by the protection of vitamin E against presynaptic protein oxidation.

Objective: In this cross-sectional study, we aimed to examine the associations between brain tocopherols and presynaptic protein levels in elderly humans.

Methods: We examined associations of α- and γ-tocopherol brain levels with presynaptic protein levels in 113 deceased participants (age 88.5±6.0 years, 45 (40%) female) from the prospective Memory and Aging project. Three distinct presynaptic proteins, a SNARE protein composite, a synaptotagmin synaptophysin composite and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25), and syntaxin were measured in two cortical brain regions. Linear regression models assessed associations of brain tocopherols with presynaptic protein levels.

Results: Higher brain γ-tocopherol levels were associated with higher levels of the SNARE protein composite, complexin-I, complexin-II, the synaptotagmin synaptophysin composite, and septin-5 in the midfrontal cortex (B(SE) = 0.272 to 0.412 (0.084 to 0.091), p < 0.001 to 0.003). When additionally adjusted for global Alzheimer’s disease pathology, cerebral infarcts, and Lewy body disease pathology, these associations remained largely similar. No associations were found between α-tocopherol and presynaptic protein levels.

Conclusion: In this cross-sectional study, we found higher brain γ-tocopherol levels were associated with presynaptic protein levels in the midfrontal cortex. These results are consistent with a proposed role of vitamin E to maintain presynaptic protein levels.

Yuka Nakatsu, Shumpei Niida, Kiyoshi Tanaka, Shigeo Takenaka, Akiko Kuwabara

J Nutr Sci Vitaminol (Tokyo) . 2020;66(3):213-218. doi: 10.3177/jnsv.66.213.

Abstract

Since vitamin E is one of the most potent antioxidant and anti-inflammatory agents, vitamin E can play a role against arteriosclerosis through various actions. Then, we have studied the relationship between serum vitamin E status and risk factors for arteriosclerosis in Japanese postmenopausal women. One hundred and seven subjects (70.0±7.7 y) were evaluated for vitamin E status by measuring serum α- and γ-tocopherol (αT and γT) levels. The number of arteriosclerosis risk factors was defined by the existence of high blood pressure, hyperglycemia, and dyslipidemia. Median serum αT and γT concentrations were 24.32 and 2.79 μmol/L, respectively. In none of the subjects, serum αT level was below the cutoff value (<12 μmol/L) for vitamin E deficiency which causes fragile erythrocyte and hemolysis. While no significant differences were found in serum levels of αT and γT between the groups categorized by the number of arteriosclerosis risks, serum levels of αT adjusted by serum total cholesterol (TC) and triglyceride (TG) decreased with an increasing number of arteriosclerotic risk factors (p=0.074). Serum αT level adjusted by serum TC and TG was also a negative significant predictor for the number of arteriosclerosis risk factors controlled by covariates associated with arteriosclerosis. The present study described that serum vitamin E level was positively associated with a lower number of arteriosclerotic risks, and its role for preventing noncommunicable diseases was suggested.

William G Christen, Amy K Darke, John M Gaziano, Robert J Glynn, Phyllis J Goodman, Lori M Minasian, Ian M Thompson Jr

Acta Ophthalmol . 2020 Jul 23. doi: 10.1111/aos.14538. Online ahead of print.

Lettter to the Editor

Selenium and vitamin E are found in the human retina and retinal pigment epithelium and have been associated with risks of age-related macular degeneration (AMD) in observational epidemiological studies (Khoo et al. 2019). We examined a possible role for these nutrients in AMD prevention in the Select Eye Endpoints (SEE) Study, an ancillary study of the National Cancer Institute-sponsored Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized, placebo-controlled trial of selenium (200 lg/d) and/or vitamin E (400 IU/d) in prevention of prostate cancer among 35 533 apparently healthy men aged 50 years and older (Lippman et al. 2005; Lippman et al. 2009).