Evaluating Anticancer and Immunomodulatory Effects of Spirulina (Arthrospira) platensis and Gamma-Tocotrienol Supplementation in a Syngeneic Mouse Model of Breast Cancer

Hemavathy Subramaiam, Wan-Loy Chu, Ammu Kutty Radhakrishnan, Srikumar Chakravarthi, Kanga Rani Selvaduray, Yih-Yih Kok

Nutrients . 2021 Jul 6;13(7):2320. doi: 10.3390/nu13072320.

Abstract

Nutrition can modulate host immune responses as well as promote anticancer effects. In this study, two nutritional supplements, namely gamma-tocotrienol (γT3) and Spirulina, were evaluated for their immune-enhancing and anticancer effects in a syngeneic mouse model of breast cancer (BC). Five-week-old female BALB/c mice were fed Spirulina, γT3, or a combination of Spirulina and γT3 (Spirulina + γT3) for 56 days. The mice were inoculated with 4T1 cells into their mammary fat pad on day 28 to induce BC. The animals were culled on day 56 for various analyses. A significant reduction (p < 0.05) in tumor volume was only observed on day 37 and 49 in animals fed with the combination of γT3 + Spirulina. There was a marked increase (p < 0.05) of CD4/CD127⁺ T-cells and decrease (p < 0.05) of T-regulatory cells in peripheral blood from mice fed with either γT3 or Spirulina. The breast tissue of the combined group showed abundant areas of necrosis, but did not prevent metastasis to the liver. Although there was a significant increase (p < 0.05) of MIG-6 and Cadherin 13 expression in tumors from γT3-fed animals, there were no significant (p > 0.05) differences in the expression of MIG-6, Cadherin 13, BIRC5, and Serpine1 upon combined feeding. This showed that combined γT3 + Spirulina treatment did not show any synergistic anticancer effects in this study model.

Haiyan Ge, Weina Liu, Huimin Li, Ming Zhang, Mengbin Zhang, Chao Liu, Yanxia Qiao

Pediatr Pulmonol . 2021 Jul;56(7):2108-2113. doi: 10.1002/ppul.25414. Epub 2021 Apr 20.

Abstract

Background: Despite improvements made in neonatal care, bronchopulmonary dysplasia (BPD) is still the most common respiratory disease in preterm infants. The relationship between the blood contents of vitamin D/E in premature infants and BPD is still controversial.

Methods: Preterm infants were recruited as the research subjects. On the basis of the inclusion and exclusion criteria, a total of 133 eligible cases were finally included. A total of 63 preterm infants with a clear diagnosis of BPD and 5 preterm infants who died before the diagnosis of BPD were in the case group, and 65 non-BPD preterm infants with equivalent baseline characteristics were in the control group. The BPD group included 38 cases in Grade Ⅰ, 18 cases in Grade Ⅱ, and 12 cases in Grade Ⅲ. The contents of vitamin D and E in the cord blood of different groups were detected by high-performance liquid chromatography and enzyme-linked immunosorbent assay. Correlation analysis adopted the Pearson correlation analytic method.

Results: The serum vitamin D and E levels at birth were remarkably lower in the BPD group than the non-BPD group, both of which were also correlated with the severity of BPD. The vitamin D and E contents were negatively correlated with the oxygen support duration required for premature infants with BPD.

Conclusion: This study deepens our understanding of the field of BPD pathogenesis by demonstrating an association between vitamin D/E deficiency and BPD severity, suggesting that vitamin D and E might have potential clinical value in the prognosis and treatment of BPD.

Gustav Dallner, Magnus Bentinger, Shafaat Hussain, Indranil Sinha, Jiangning Yang, Cheng Schwank-Xu, Xiaowei Zheng, Ewa Swiezewska, Kerstin Brismar, Ismael Valladolid-Acebes, Michael Tekle

Antioxidants (Basel) . 2021 Jul 2;10(7):1070. doi: 10.3390/antiox10071070.

Abstract

Hyperglycemia, hyperlipidemia, and adiposity are the main factors that cause inflammation in type 2 diabetes due to excessive ROS production, leading to late complications. To counteract the effects of increased free radical production, we searched for a compound with effective antioxidant properties that can induce coenzyme Q biosynthesis without affecting normal cellular functions. Tocotrienols are members of the vitamin E family, well-known as efficient antioxidants that are more effective than tocopherols. Deh-T3β is a modified form of the naturally occurring tocotrienol-β. The synthesis of this compound involves the sequential modification of geranylgeraniol. In this study, we investigated the effects of this compound in different experimental models of diabetes complications. Deh-T3β was found to possess multifaceted capacities. In addition to enhanced wound healing, deh-T3β improved kidney and liver functions, reduced liver steatosis, and improved heart recovery after ischemia and insulin sensitivity in adipose tissue in a mice model of type 2 diabetes. Deh-T3β exerts these positive effects in several organs of the diabetic mice without reducing the non-fasting blood glucose levels, suggesting that both its antioxidant properties and improvement in mitochondrial function are involved, which are central to reducing diabetes complications.

Nurliyana Najwa Md Razip, Banulata Gopalsamy, Mohd Sokhini Abdul Mutalib, Sui Kiat Chang, Muhammad Mikhail Joseph Anthony Abdullah, Azrina Azlan, Zulida Rejali, Huzwah Khaza'ai

Nutrients . 2021 Jul 1;13(7):2288. doi: 10.3390/nu13072288.

Abstract

An overview of vitamins D₃ and E suggests micronutrient deficiency contributes to type 2 diabetes mellitus (T2DM). A case-control study was conducted to determine the status of plasma vitamins D₃ and E isomers amongst diabetic Malaysians. Two groups were recruited for participation, one comprising fifty diabetic subjects (DM) and one comprising fifty non-diabetic (non-DM) subjects, in order to assess their plasma vitamin D₃, calcium and vitamin E status. Glycaemic status (haemoglobin A1c, HbA1c; fasting blood glucose, FBG; C-Peptide) and lipid profiles (total cholesterol, TC; triglycerides, TG; low-density lipoprotein-cholesterol, LDL-C; high-density lipoprotein-cholesterol, HDL-C) were assessed, followed by anthropometric measurements. The Mann-Whitney U-test, Kruskal-Wallis and Spearman’s correlation coefficient were used to elucidate the association between levels of plasma vitamins D₃ and E and T2DM. The vitamin D₃ deficiency group (<20 ng/mL) showed a significant correlation (p < 0.05) with glycaemic status (HbA1c and FBG) and lipid profiles (HDL-C, LDL and TC). Spearman’s correlation demonstrated that vitamin D₃ status is strongly correlated with HDL levels (p < 0.05). Similarly, plasma total vitamin E levels >4.9 μg/mL revealed significantly different FBG, HbA1c, C-Peptide, LDL, HDL and TC levels across both groups. Moreover, family history, smoking, waist circumference and HbA1c levels demonstrated a significant association (p < 0.05) with levels of vitamins D and E but not FBG and lipid profiles. This could be because the pre-diabetic status among the non-DM group influenced the outcomes of this study.

Francesca Gamna, Silvia Spriano

Materials (Basel) . 2021 Jul 1;14(13):3691. doi: 10.3390/ma14133691.

Abstract

Vitamin E is a common compound used for tocopherols and tocotrienols (α, β, γ, δ); it is the component of many natural products of both plant and animal origin. Thanks to its powerful antioxidant capacity, vitamin E has been very successful in hip and knee arthroplasty, used to confer resistance to oxidation to irradiated UHMWPE. The positive results of these studies have made vitamin E an important object of research in the biomedical field, highlighting other important properties, such as anti-bacterial, -inflammatory, and -cancer activities. In fact, there is an extensive literature dealing with vitamin E in different kinds of material processing, drug delivery, and development of surface coatings. Vitamin E is widely discussed in the literature, and it is possible to find many reviews that discuss the biological role of vitamin E and its applications in food packaging and cosmetics. However, to date, there is not a review that discusses the biomedical applications of vitamin E and that points to the methods used to detect it within a solid. This review specifically aims to compile research about new biomedical applications of vitamin E carried out in the last 20 years, with the intention of providing an overview of the methodologies used to combine it with implantable biomaterials, as well as to detect and characterize it within these materials.

J D Quigley, T M Hill, T S Dennis, F X Suarez-Mena, W Hu, S Kahl, T H Elsasser

J Dairy Sci . 2021 Jul 1;S0022-0302(21)00702-5. doi: 10.3168/jds.2020-19929. Online ahead of print.

Abstract

Vitamin E comprises 8 fat-soluble isoforms: α-, β-, γ-, and δ-tocopherol and α-, β-, γ-, and δ-tocotrienol. Yet the body preferentially uses α-tocopherol, and only α-tocopherol supplementation can reverse vitamin E deficiency symptoms. However, other isoforms influence many biological functions in the body, including inflammation and stress. Therefore, the study objective was to determine metabolic and performance responses in young calves fed diets containing a constant amount of α-tocopherol and increasing amounts of soybean oil-derived mixed γ- and δ-tocopherols. Holstein calves [n = 48; 2-3 d of age; 40.2 kg of initial body weight (BW), standard error = 0.54] were assigned to receive approximately 0, 5, 10, or 15 mg/kg of BW daily (treatments T0, T1, T2, and T3, respectively) of mixed tocopherols (TMIX) provided in milk replacer (MR) and calf starter. The TMIX liquid contained 86% γδ-tocopherols and 9% α-tocopherol. Milk replacers were formulated to contain approximately 0, 400, 800, or 1,200 mg of TMIX/kg for treatments T0, T1, T2, and T3, respectively. Calf starters were formulated to contain approximately 0, 250, 500, or 750 mg of TMIX/kg for treatments T0, T1, T2, and T3, respectively. Mean consumption of γδ-tocopherols was 0.0, 6.5, 14.3, and 20.5 mg/kg of BW, respectively. Milk replacer contained 24% crude protein (CP) and 20% fat on a dry matter (DM) basis. Calf starters were pelleted and offered for ad libitum consumption from 0 to 56 d. Starters contained 18 to 20% CP and 9 to 12% starch in the DM. On d 28, 4 calves per treatment were randomly selected for slaughter, and necropsy was performed. Samples of liver, duodenum, ileum, and trapezius muscle were collected and stored before analysis for α-, β-, γ-, and δ-tocopherols and δ-tocotrienol. Data were analyzed using a completely randomized design using mixed model ANOVA with orthogonal polynomials to determine linear and quadratic effects of TMIX. Repeated-measures analyses were performed for data collected over time. Increasing dietary TMIX increased or tended to increase change in hip width at 28 and 56 d, respectively, and improved average daily BW gain and gain-to-feed ratio at 56 d. Increasing TMIX reduced plasma xanthine oxidase at 0 h and tended to reduce concentrations at 24 h following vaccination with 2 commercial vaccines on d 28; however, we detected no effect of TMIX following vaccination on d 56. Concentration of α-tocopherol in skeletal muscle declined quadratically with increasing TMIX, whereas ileal and liver γ-tocopherol increased linearly with increasing TMIX. The number of mucin-2 cells in the ileum increased more than 2-fold in calves fed T3. Addition of mixed tocopherols to diets of young dairy calves improved animal growth and altered indices of antioxidant metabolism.

Maral Barzegar-Amini, Fateme Khorramruz, Hamideh Ghazizadeh, Reza Sahebi, Maryam Mohammadi-Bajgyran, Hossein Mohaddes Ardabili, Maryam Tayefi, Susan Darroudi, Mohsen Moohebati, Alireza Heidari-Bakavoli, Akram Mohammadi, Hamid Reza Sadeghnia, Gordon A Ferns, Seyed Javad Hoseini, Majid Ghayour Mobarhan

Acta Biomed . 2021 Jul 1;92(3):e2021047. doi: 10.23750/abm.v92i3.9173.

Abstract

Background: Metabolic syndrome (MetS) is a cluster of clinical and metabolic features that include central obesity, dyslipidemia, hypertension and impaired glucose tolerance. These features are accompanied by increased oxidative stress and impaired antioxidant defenses. Vitamin E is a major factor in the non-enzymatic antioxidant defenses. The aim of present study was to investigate the association between serum levels of vitamin E and the presence of MetS and its components in a sample population of Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study.

Methods: This cross-sectional study was carried out in 128 subjects with MetS and 235 subjects without MetS. MetS was defined according to the International-Diabetes-Federation criteria. Serum levels of vitamin E were measured using the HPLC method. Anthropometric and biochemical parameters were measured using standard protocols. Results. MetS patients had significantly lower serum levels of vitamin E (Vit E), Vit E/Total cholesterol (TC), and Vit E/ (TC+triglyceride(TG)) compared to the control group (P < 0.05). Vit E/ (TG+TC) was also significantly lower in diabetics or those with elevated levels of high sensitive C-reactive protein (hs-CRP). Additionally, there was a significant association between Vit E/ (TG + Total Cho) and the number of components of the metabolic syndrome (p= 0.02) Conclusions. There is a significant inverse association between indices of Vit E status and the presence of MetS. Moreover, a significantly lower Vit E/ (TC+TG) was observed along with individuals with increasing numbers of components of the MetS.

Leila Azouaou Toualbi, Adnane Mounir, Ballouti Wafa, Arab Medina, Khelfi Abderrezak, Toualbi Chahine, Chader Henni, Bennoui Abdelghani, Seba Atmane

Arch Med Sci Atheroscler Dis . 2021 Jun 30;6:e135-e144. doi: 10.5114/amsad.2021.107823. eCollection 2021.

Abstract

Introduction: Advanced oxidation protein products (AOPP) are considered as markers of oxidative stress and inflammation, and highly predictive of atherosclerosis. Vitamin E (Vit-E) is a powerful antioxidant, but no consensus on its effectiveness at the level of AOPP or the process of atherosclerosis has been made. Hence this was the aim of the present study.

Material and methods: A longitudinal study was conducted on 205 patients with chronic kidney disease (CKD) and 40 controls. The correlations between AOPP and glomerular filtration rate (GFR) and different biological markers were analyzed. Supra-aortic trunk echo-Doppler was conducted to assess the correlation of AOPP with intima-media thickness. The effects of Vit-E treatment on AOPP levels and atherosclerosis progression were also investigated.

Results: AOPP levels increased in parallel to the alteration of renal functions in CKD patients, compared to the control group (p < 0.05). The mean value of AOPP increased concomitantly with the intima-media thickness (p < 0.05). Furthermore, AOPP mean value was higher in patients with atherosclerotic plaques (p < 0.05) compared to those without plaques. Vit-E treatment stabilized the levels of AOPP but had no effect on the atherosclerotic progression.

Conclusions: AOPP were proved to be effective markers of oxidative stress and their high levels help to predict the progression of atherosclerosis. As a powerful antioxidant, Vit-E stabilized the AOPP levels.

Zhuo Chen, Zhicai Zuo, Kejie Chen, Zhuangzhi Yang, Fengyuan Wang, Jing Fang, Hengmin Cui, Hongrui Guo, Ping Ouyang, Zhengli Chen, Chao Huang, Yi Geng, Wentao Liu, Huidan Deng

Biol Trace Elem Res . 2021 Jun 25. doi: 10.1007/s12011-021-02784-1. Online ahead of print.

Abstract

Cadmium (Cd), a heavy metal element, cumulates in the testis and can cause male reproductive toxicity. Although vitamin E (VE) as one of potential antioxidants protects the testis against toxicity of Cd, the underlying mechanism remained uncompleted clear. The aim of this study was to investigate whether the Nrf-2 pathway is involved with the protective effect of VE on testicular damages caused by sub-chronic Cd exposure. Thirty-two SD rats were divided into four groups and orally administrated with VE and/or Cd for 28 consecutive days: control group, VE group (100 mg VE/kg), Cd group (5 mg CdCl₂/kg), and VE + Cd group (100 mg VE/kg + 5 mg CdCl₂/kg). The results showed that 28-day exposure of Cd caused accumulation of Cd, histopathological lesions, and alternations of sperm parameters (elevated rate of abnormal sperm, decreased count of sperm, declined motility, and viability of sperm). Moreover, the rats exposed to Cd showed significant oxidative stress (increased contents of MDA and decreased levels or activities of T-AOC, GSH, CAT, SOD and GSH-Px) and inhibition of Nrf-2 signaling pathway (downregulation of Nrf-2, HO-1, NQO-1, GCLC, GCLM and GST) of the testes. In contrast, VE treatment significantly reduced the Cd accumulation, alleviated histopathological lesions and dysfunctions, activated Nrf-2 pathway, and attenuated the oxidative stress caused by Cd in the testes of rats. In conclusion, VE, through upregulating Nrf-2 pathway, could protect testis against oxidative damages induced by sub-chronic Cd exposure.

Mehmet Arif Icer, Neslihan Arslan, Makbule Gezmen-Karadag

Acta Neurobiol Exp (Wars) . 2021;81(1):21-33. doi: 10.21307/ane-2021-003.

Abstract

Vitamin E deficiency is associated with many neurological problems. Although the mechanisms of vitamin E action in neurodegenerative diseases are not clear, there are many possible mechanisms. Examples of such mechanisms are the protective effects of vitamin E against oxidative stress damage and its suppressive role in the expression of many genes involved in the development of neurodegeneration. Many studies have evaluated the relationship between vitamin E intake or vitamin E levels in body fluids and neurodegenerative diseases. Some studies concluded that vitamin E can play a protective role in neurodegeneration with respect to diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke and amyotrophic lateral sclerosis (ALS). Vitamin E supplementation was also associated with risk factors for some neurodegenerative diseases. In this review, we discuss the possible effects of vitamin E on the development and course of AD, PD, stroke and ALS, and the potential mechanisms involved.