Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain

Rita Marinelli, Pierangelo Torquato, Desirée Bartolini, Cristina Mas-Bargues, Guido Bellezza, Antimo Gioiello, Consuelo Borras, Antonella De Luca, Francesca Fallarino, Bartolomeo Sebastiani, Sridhar Mani, Angelo Sidoni, Jose Viña, Manuela Leri, Monica Bucciantini, Pamela Nardiello, Fiorella Casamenti, Francesco Galli

J Biol Chem . 2020 Aug 14;295(33):11866-11876. doi: 10.1074/jbc.RA120.013303. Epub 2020 Jul 2.

Abstract

Garcinoic acid (GA or δ-T3-13’COOH), is a natural vitamin E metabolite that has preliminarily been identified as a modulator of nuclear receptors involved in β-amyloid (Aβ) metabolism and progression of Alzheimer’s disease (AD). In this study, we investigated GA’s effects on Aβ oligomer formation and deposition. Specifically, we compared them with those of other vitamin E analogs and the soy isoflavone genistein, a natural agonist of peroxisome proliferator-activated receptor γ (PPARγ) that has therapeutic potential for managing AD. GA significantly reduced Aβ aggregation and accumulation in mouse cortical astrocytes. Similarly to genistein, GA up-regulated PPARγ expression and apolipoprotein E (ApoE) efflux in these cells with an efficacy that was comparable with that of its metabolic precursor δ-tocotrienol and higher than those of α-tocopherol metabolites. Unlike for genistein and the other vitamin E compounds, the GA-induced restoration of ApoE efflux was not affected by pharmacological inhibition of PPARγ activity, and specific activation of pregnane X receptor (PXR) was observed together with ApoE and multidrug resistance protein 1 (MDR1) membrane transporter up-regulation in both the mouse astrocytes and brain tissue. These effects of GA were associated with reduced Aβ deposition in the brain of TgCRND8 mice, a transgenic AD model. In conclusion, GA holds potential for preventing Aβ oligomerization and deposition in the brain. The mechanistic aspects of GA’s properties appear to be distinct from those of other vitamin E metabolites and of genistein.

Jun Yang, Xuemei Ding, Shiping Bai, Jianping Wang, Qiufeng Zeng, Huanwei Peng, Yue Xuan, Zuowei Su, Keying Zhang

Animals (Basel) . 2020 Aug 13;10(8):E1409. doi: 10.3390/ani10081409.

Abstract

This study was conducted to investigate the effects of broiler breeder dietary vitamin E and egg storage time on the egg characteristics, hatchability, and antioxidant status of the egg yolks and newly hatched chicks. A total of 512 71-week-old Ross 308 breeder hens were fed the same basic diets containing 6 or 100 mg/kg vitamin E for 12 weeks. During this time, a total of 1532, 1464, and 1316 eggs were independently collected at weeks 8, 10, and 12, respectively, and subsequently stored for 0 or 14 d before hatching. The outcomes from three trials showed that prolonged egg storage time (14 vs. 0 d) negatively affected (p < 0.05) the egg characteristics, hatchability traits, and the yolk total antioxidant capacity (T-AOC) (p < 0.05). Chicks derived from the stored eggs exhibited higher malonaldehyde (MDA) and T-AOC in the serum and yolk sac (p < 0.05). Broiler breeder dietary vitamin E (100 vs. 6 mg/kg) increased (p < 0.05) the hatchability and the antioxidant status of the yolks as indicated by a higher α-tocopherol content and T-AOC and lower MDA level (p < 0.05). The supplementation of vitamin E also remarkably increased (p < 0.05) the total superoxide dismutase (T-SOD) activity (yolk sac, weeks 8 and 12) and T-AOC (serum, weeks 8, 10, and 12; yolk sac, weeks 8 and 12) and decreased (p < 0.05) the MDA content of chicks (yolk sac, week 10; serum, week 12). Interactions (p < 0.05) were found between the broiler breeder dietary vitamin E and egg storage time on the hatchability and antioxidant status of chick tissues. Broiler breeder dietary vitamin E (100 vs. 6 mg/kg) increased (p < 0.05) the hatchability and the T-AOC in the serum and liver of chicks, and decreased (p < 0.05) the early embryonic mortality and the MDA content in the yolk sacs of chicks derived from eggs stored for 14 d but not for 0 d. In conclusion, prolonged egg storage time (14 vs. 0 d) increased the embryonic mortality, decreased the hatchability, and impaired the antioxidant status of egg yolks and newly hatched chicks, while the addition of broiler breeder dietary vitamin E (100 vs. 6 mg/kg) could partly relieve these adverse impacts induced by long-term egg storage.

Fahaid Al-Hashem, Mohamed Abd Ellatif, Asmaa M ShamsEldeen, Samaa S Kamar, Bahjat Al-Ani, Mohamed A Haidara

Arch Physiol Biochem . 2020 Aug 12;1-9. doi: 10.1080/13813455.2020.1806330. Online ahead of print.

Abstract

Background: Acute pancreatitis (AP) associated with the modulation of TNF-α-AMPK axis in the presence and absence of vitamin E has not been investigated before.

Material and methods: Rats were either injected with L-arginine (2.5 gm/kg) before being sacrificed after 48 h or were pre-treated with vitamin E (60 mg/kg) and continued receiving vitamin E until the end of the experiment.

Results: AP was developed as demonstrated by infiltration of inflammatory cells and profound pancreas tissue damage, which were substantially protected by vitamin E. In addition, L-arginine injections significantly (p < .0001) increased the expression of TNF-α mRNA and protein, and decreased phospho-AMPK and IL-10 mRNA and protein that was significantly (p < .0001) protected by vitamin E. Furthermore, vitamin E inhibited L-arginine-induced blood levels of LDH, amylase, and myeloperoxidase.

Conclusions: L-arginine-induced acute pancreatitis modulates TNF-α-AMPK axis, IL-10 and other AP biomarkers, which is protected by vitamin E; thus, may offer therapeutic potential in humans.

Madison M Fagan, Patricia Harris, Amanda Adams, Robert Pazdro, Amber Krotky, Jarrod Call, Kylee J Duberstein

J Equine Vet Sci . 2020 Aug;91:103103. doi: 10.1016/j.jevs.2020.103103. Epub 2020 Apr 29.

Abstract

Vitamin E is an essential antioxidant that may benefit athletes by reducing oxidative stress and influencing cytokine expression. Supplements can be derived from natural or manufactured synthetic sources. This study aimed to determine (1) if supplemental vitamin E is beneficial to exercising horses and (2) if there is a benefit of natural versus synthetic vitamin E. After 2 weeks on the control diet (vitamin E-deficient grain and hay), 18 horses were divided into three groups and fed the control diet plus (1) 1000 IU/d synthetic α-tocopherol (SYN-L), (2) 4000 IU/d synthetic α-tocopherol (SYN-H), or (3) 4000 IU/d RRR-α-tocopherol (natural source [NAT]). On day 7, horses began a 6-week training protocol, with standard exercise tests (SETs) performed before and after the 6-week protocol. Venous blood samples were collected on days 0, 7, 29, and 49. Horses fed NAT had higher α-tocopherol (P < .05) at post-SET1 through post-SET2. Plasma thiobarbituric acid-reactive substance levels were lower in NAT versus SYN-L horses after SET2 (P = .02). Serum aspartate aminotransferase was lower after exercise in NAT horses versus SYN-L and SYN-H (P = .02), and less reduction in stride duration was seen after exercise in NAT as compared with SYN-L and SYN-H (P = .02). Gene expression of tumor necrosis factor α was lower in NAT compared with SYN-H (P = .01) but not SYN-L. In conclusion, feeding higher levels of natural vitamin E source resulted in higher serum α-tocopherol levels as well as some improvement in oxidative and inflammatory response and improved functional outcomes in response to an exercise test.

Azza M A Abo-Elmaaty, Amany Behairy, Nesma I El-Naseery, Mohamed M Abdel-Daim

Environ Sci Pollut Res Int . 2020 Aug 7. doi: 10.1007/s11356-020-10351-9. Online ahead of print.

Abstract

Cisplatin (CP) is a highly effective chemotherapeutic agent against neoplasms, but its clinical utility is limited due to the side effects of its dose-dependent nephrotoxicity. Vitamin E (Vit E) and cod liver oil (CLO) are natural substances with chemoprotective effects. The present study was conducted to evaluate the protective effects of Vit E and/or CLO for CP-induced acute kidney injury (AKI) in rats. This study involved 40 mature male Wistar albino rats that were equally allocated into eight groups: Veh, Vit E, CLO, Vit E + CLO, CP, Vit E + CP, CLO + CP, and Vit E + CLO + CP. The co-administration of Vit E and CLO significantly ameliorated CP-induced elevations in serum creatinine (Cr), blood urea nitrogen (BUN), interleukin 1 beta (IL-1β), and interleukin- 6 (IL-6). Further, rats that received Vit E and/or CLO showed significant decrease in malondialdehyde (MDA) and increases in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels in renal tissues, compared to CP-intoxicated rats. Additionally, the treatment restored the normal histological architecture (except for few cast formations) and upregulated the immunostaining area% of aquaporin 3 (AQP3) and downregulated the immunostaining area% of Bcl2 associated X protein (BAX) and inducible nitric oxide synthase (iNOS). The observed effects were stronger in the combination treatment group. The obtained data revealed that Vit E and CLO co-administration protects against the CP-induced AKI more than monotherapy with Vit E or CLO.

Panagiotis Theodosis-Nobelos, Georgios Papagiouvannis, Eleni A Rekka

Mini Rev Med Chem . 2020 Aug 7. doi: 10.2174/1389557520666200807132617. Online ahead of print.

Abstract

Vitamin E, essential for human health, is widely used worldwide for therapeutic or dietary reasons. The differences in the metabolism and excretion of the multiple vitamin E forms are presented in this review. The important steps that influence the kinetics of each form and the distribution and processing of vitamin E forms by the liver are considered. The antioxidant as well as non-antioxidant properties of vitamin E forms are discussed. Finally, synthetic tocopherol and trolox derivatives, based on the design of multitarget directed compounds, are reviewed. It is demonstrated that selected derivatization of vitamin E or trolox structures can produce improved antioxidants, agents against cancer, cardiovascular and neurodegenerative disorders.

F Sánchez-Rubio, P J Soria-Meneses, A Jurado-Campos, J Bartolomé-García, V Gómez-Rubio, A J Soler, M M Arroyo-Jimenez, M J Santander-Ortega, M Plaza-Oliver, M V Lozano, J J Garde, M R Fernández-Santos

Free Radic Biol Med . 2020 Aug 5;160:47-56. doi: 10.1016/j.freeradbiomed.2020.07.024. Online ahead of print.

Abstract

Vitamin E is considered a powerful biological antioxidant; however, its characteristics such as high hydrophobicity and low stability limit its application. We propose to use nanotechnology as an innovative tool in spermatology, formulating nanoemulsions (NE) that accommodate vitamin E, protecting it from oxidation and promoting its release into the medium. The protective effect of the NE against oxidative stress was assessed in red deer epididymal sperm incubated at 37 °C. Cryopreserved sperm from eleven stags were thawed and extended to 400 × 10⁶ sperm/ml in Bovine Gamete Medium (BGM). Once aliquoted, the samples were supplemented with the NE at different concentrations (0, 6 and 12 mM), with or without induced oxidative stress (100 μM Fe²⁺/ascorbate). The samples were evaluated after 0, 2 and 4 h of incubation at 37 °C. Motility (CASA), viability, mitochondrial membrane potential, acrosomal status, lipoperoxidation (C11 BODIPY 581/591), intracellular reactive oxygen species (ROS) production and DNA status (SCSA®) were assessed. After 2 and 4 h of incubation, the NE were able to prevent the deleterious effects of oxidative stress, thus improving total and progression motility (P ˂0.05). Moreover, the highest concentration tested (12 mM) improved almost every sperm kinematic variable (P ˂0.05) and preserved sperm viability in samples subjected to oxidative stress. In addition, 12 mM of NE protected the acrosomes integrity, maintained and protected mitochondrial activity, prevented sperm lipoperoxidation and reduced ROS production (P ˂0.05) in samples subjected to oxidative stress. This work indicates for the first time that vitamin E formulated in NE could be a new approach against sperm oxidative damage. This could be highly relevant for sperm physiology preservation in the context of assisted reproduction techniques.

Hiren Patel, Daisy Shirk, Joshua Lowery

J Child Adolesc Psychopharmacol . 2020 Aug 3. doi: 10.1089/cap.2020.0042. Online ahead of print.

To the Editor: Introduction Elevated transaminases are a common complication of many drugs, occurring in up to 27% of patients taking atypical antipsychotics medications (Atasoy et al. 2007). For patients who have no other options than remaining on certain antipsychotics such as olanzapine, physicians must weigh the risks versus benefits of continuing antipsychotic medications. We present a case study that attempted to replicate a previous single case study in which vitamin E therapy successfully reduced damaging effects of olanzapine on liver enzymes (Do¨nmez et al. 2017).

Flavia Kazue Ibuki, Cassia T Bergamaschi, Marlus da Silva Pedrosa, Fernando Neves Nogueira

Arch Oral Biol . 2020 Aug;116:104765. doi: 10.1016/j.archoralbio.2020.104765. Epub 2020 May 16.

Abstract

Objective: We examined the effects of vitamin C and E supplementation in the prevention of oxidative stress in the salivary glands of STZ-induced diabetic rats.

Design: Forty-eight male Wistar rats were divided into six groups (n = 8 in each): control (C), control supplemented with vitamin C (Cvc) and E (Cve), diabetic (D), and diabetic supplemented with vitamin C (Dvc) and E (Dve). Vitamin C (150 mg/kg) and E (300 mg/kg) were daily administered for 21 days. Serum ascorbic acid and α-tocopherol levels were quantified. Glandular levels of hydrogen peroxide (H₂O₂), superoxide anion (O₂^–), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), malondialdehyde (MDA) and the total antioxidant status (TAS) were estimated.

Results: Vitamin C and E levels were reduced in D group. Vitamin C decreased the levels of O₂^– in the salivary gland of diabetic rats. Vitamin E increased the concentration of O₂^– in PA gland of diabetic animals. In the SM gland of the diabetic group, MDA, SOD, GPx and TAS increased. Dve presented reduced SOD activity and increased GR, GPx, and MDA. Dve increased GPx, Gr and TAS levels. In the PA gland, MDA, SOD, CAT, GPx, GR, and TAS were similar in C and D. TAS, SOD, CAT, GPx, and GR increased in Dvc. Vitamin E supplementation resulted in increased MDA and CAT levels and reduced SOD activity.

Conclusion: In the SM glands of the diabetic rats, vitamin C supplementation improved the antioxidant system, while vitamin E acted as pro-oxidant.

Shi-Yi Wang, Yin-Feng Wang, Chun-Chen Pan, Jing-Wu Sun

BMC Pediatr . 2020 Jul 31;20(1):362. doi: 10.1186/s12887-020-02248-w.

Abstract

Background: Allergic rhinitis (AR) is one of the most prevalent allergic diseases in children. This study aimed to investigate the association between serum concentrations of vitamin E and AR to determine if the vitamin E level is correlated with the occurrence and severity of AR.

Methods: A total of 113 children were enrolled in this cross-sectional study. Sixty-five children in the outpatient group were diagnosed with AR, and 48 healthy children were recruited as controls. All subjects underwent serum vitamin E (adjusted for total cholesterol and triglycerides) measurements. Serum to total IgE (tIgE), the five most common allergen-specific IgE (sIgE) levels and skin prick test (SPT) were measured in children with AR. The severity of AR was assessed with the nasal symptoms score, and the situation of exposure to passive smoking were inquired.

Results: Serum vitamin E levels were significantly lower in the AR group than in the normal children (P < 0.001). A significant negative correlation was observed between serum vitamin E levels and sIgE as well as the SPT grade. Serum vitamin E levels were also inversely related to the nasal symptoms score; however, statistical significance was not found.

Conclusions: A significantly lower vitamin E level was found in children with AR. Lower serum vitamin E levels may have correlation with the occurrence of AR in children. However, serum vitamin E levels were not statistically correlated with the severity of AR.