Protective Effects of Vitamin E on Aluminium Sulphate-Induced Testicular Damage

Ozal Ulfanov, Nazli Cil, Esat Adiguzel

Toxicol Ind Health . 2020 Apr 24;748233720919663. doi: 10.1177/0748233720919663.

Abstract

Male infertility can be caused by environmental factors, genetic defects, physiological and endocrine deficiencies and testicular pathologies. Aluminium (Al) can cause male infertility through a number of mechanisms. The aim of our study was thus to determine whether vitamin E (VitE) has protective effects on Al-induced testicular damage, which was determined according to sperm counts and morphology and using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Thirty-four male Wistar rats (250-300 g) were randomly assigned to control (no procedures performed; n = 6) or 0.2 mL intraperitoneal injection group (n = 7 each; three times per week for 4 weeks): sham (distilled water), 10 mg/kg Al, 500 mg/kg VitE and 10 mg/kg Al plus 500 mg/kg VitE (Al + VitE). Sperm samples were evaluated for andrological parameters. The testes were examined by haematoxylin/eosin. The epithelial thickness and areas were calculated and Johnsen scores were determined for the germinal epithelium; the apoptotic indices were determined from TUNEL staining. For Al, the bonds between the germinal epithelial cells were broken in some tubules, and there were unidentified cells in the lumen of some tubules. For control, sham and VitE, normal morphology of the germinal epithelium was generally preserved. With Al + VitE, the full germinal epithelium cell series was maintained, with only mature sperm in the lumen. TUNEL-positive cells were significantly higher with Al compared to control and sham (p < 0.05). For Al + VitE, the number of apoptotic cells was reduced compared to Al alone and was therefore similar to control, sham and VitE (p > 0.05). Our findings show that Al caused testicular damage. VitE reduced the number of apoptotic cells during the damage caused by Al.

Yue Yang, Yunjian Li, Kai Chen, Ling Zhang, Sen Qiao, Guoxin Tan, Fen Chen, Weisan Pan

Int J Nanomedicine . 2020 Apr 24;15:2885-2902. doi: 10.2147/IJN.S249205.

Abstract

Purpose: Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential.

Methods: The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by ¹H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles.

Results: The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity.

Conclusion: Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.

Mohamed Aboubakr, Faten Elsayd, Ahmed Soliman, Sabreen Ezzat Fadl, Anwar El-Shafey, Ehab Yahya Abdelhiee

Environ Sci Pollut Res Int . 2020 Apr 23. doi: 10.1007/s11356-020-08919-6.

Abstract

The present study aimed to investigate the possible mitigating effect of L-carnitine (LC) and/or α-tocopherol (Vit. E) administration against tilmicosin (TIL)-induced cardiotoxicity in rats. Fifty-six male albino rats were divided into seven groups according to LC, Vit. E, and/or TIL administration. Control, LC, and Vit. E groups were given saline, 150 mg LC/kg body weight (BW)/day and 100 mg Vit. E/kg BW/day, respectively, orally once daily for 15 days. The TIL group was administered saline orally once daily for 15 days and a single dose of TIL (75 mg/kg BW) subcutaneously (SC) on day 14 from the starting of the experimental period (15 days). The TIL-LC, TIL-Vit. E, and TIL-LC-Vit. E groups received 150 mg LC/kg BW/day, 100 mg Vit. E/kg BW/day, and 150 mg LC/kg BW pulse 100 mg Vit. E/kg BW, respectively, orally once daily for 15 days with TIL as described above. The results revealed that the administration of TIL significantly (P ≤ 0.05) raised serum activities of heart injury indicators, lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB with substantial increase (P ≤ 0.05) in the cardiac contents of malondialdehyde (MDA) and decreased in antioxidants. The pathological changes appeared in the form of necrotic muscle fibers and massive inflammatory cellular infiltrations in the cardiac muscle and increased the caspase-3 immunohistochemical expression in the heart tissues as well. These changes were ameliorated by LC and/or Vit. E administration. In conclusion, supplementation of LC and/or Vit. E ameliorated the cardiotoxicity of the TIL SC injection in the rat.

Mulliez MA, Schilling C, Grupp TM

Biomed Res Int. 2020 Mar 23;2020:2568428. doi: 10.1155/2020/2568428. eCollection 2020.

Abstract

Previous studies have shown that increased cross-link density, reduced free radicals, and increased antioxidant grafting resulting from electron-beam irradiation at elevated temperatures improved the wear performance and the oxidative stability of vitamin E blended UHMWPE. The current study explores the impact of elevated irradiation temperature on vitamin E blended UHMWPE using X-ray. We hypothesize that the effects of temperature would be similar to those observed after electron-beam irradiation due to the relatively high dose rate of X-rays. Two X-ray doses of 80 and 100 kGy and two irradiation temperatures, that is, room temperature and 100°C were considered. The reference was Vitelene®, a vitamin E stabilized polyethylene cross-linked with 80 kGy by e-beam at 100°C. Oxidation index and oxidation induction time, as well as cross-link density, gel fraction, and trans-vinylene index, were determined, as the oxidative and network properties are decisive for the long-term implant performance. Gel fraction and oxidation induction time were significantly improved subsequently to warm irradiation in comparison with the material irradiated at room temperature. In conclusion, X-ray irradiation at elevated temperatures resulted in an increase of cross-linking and oxidative resistance of vitamin E stabilized polyethylene comparable to those of e-beam irradiated UHMWPE.

Geping Wu, Hongyan Zhu, Xinyang Wu, Lili Liu, Xingkai Ma, Yifang Yuan, Xingli Fu, Ling Zhang, Yan Lv, Di Li, Jianyong Liu, Jianbin Lu, Yan Yu, Menglin Li

Allergol Immunopathol (Madr) . 2020 Apr 22;S0301-0546(20)30036-7. doi: 10.1016/j.aller.2019.11.005.

Abstract

Background: Alpha-Tocopherol (α-TCP), one major form of vitamin E, has been known as a treatment for airway allergic inflammation. However, the role and mechanism of α-TCP in treating allergic rhinitis remains unclear.

Objective: In this study we examined the inhibitory function of α-TCP in a mouse model of allergic rhinitis.

Methods: Allergic phenotype was examined by hematoxylin and eosin staining. Total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were examined by ELISA. mRNA expression was measured by qPCR, protein levels were examined by Western Blot.

Results: Histological analysis of the nasal membranes revealed that there was a significant reduction in inflammatory cells appearance in cross-sections in alpha-TCP treatment of Ovalbumin (OVA)-sensitized mice compared to OVA sensitized animals. In addition, eosinophils were significantly reduced in nasal mucosa of alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Lower total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were found in alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Furthermore, we found that the subepithelial distribution of tryptase positive mast cells was reduced in the alpha-TCP treatment of OVA-sensitized mice. More importantly, the PI3K-PKB pathway was suppressed by α-TCP in mast cells.

Conclusions: Our results demonstrated that α-TCP-mediated suppression of PI3K-PKB activity in mast cells is a potential mechanism of anti-allergic function of α-TCP.

Ran Tao, Chengzhang Wang, Yin Lu, Changwei Zhang, Hao Zhou, Hongxia Chen, WenJun Li

Int J Nanomedicine . 2020 Apr 22;15:2733-2749. doi: 10.2147/IJN.S249773.

Abstract

Background: This study demonstrated an innovative formulation including the polyprenol (GBP) lipid and vitamin E-TPGS hybrid nanoparticles (NPs) which was aimed to control the transfer of betulinic acid (BA) and low-substituted hydroxyl fullerenol (C₆₀(OH)_n). Additionally, it developed BA-C₆₀(OH)n-GBP-TPGS-NPs delivery system and researched the anti-hepatocellular carcinoma (HCC) effects.

Materials and methods: The NPs were prepared by nanoprecipitation with ultrasonic-assisted emulsification (UAE) method. It was characterized by scanning electronic microscopy (SEM), transmission electron microscopy (TEM), FTIR spectrum, size distribution and zeta potential. Physical and chemical properties were evaluated through measurement of drug release, stability studies, drug loading efficiency (DE) and encapsulation efficiency (EE). Biological activities were evaluated through measurement of MTT assay, lactate dehydrogenase leakage assay (LDH), cell proliferation assays, cell apoptosis analysis, comet assay, wound healing assay, cell invasion and Western blot analysis.

Results and conclusions: The NPs exhibited clear distribution characteristics, improved solubility and stability. BA and C₆₀(OH)_n for the NPs displayed a biphasic release pattern with sustained drug release properties. The mixture of C₆₀(OH)_n with different hydroxyl groups may have a certain effect on the stability of the NPs system itself. The NPs could effectively inhibit MHCC97H cell proliferation, migration and invasion in vitro. Combined use of C₆₀(OH)_n and BA in GBP lipids may improve the inhibit effect of C₆₀(OH)_n or BA against HCC cells and reduce cytotoxicity and genotoxicity of C₆₀(OH)_n for normal cells. We concluded that one of the important mechanisms of BA-C₆₀(OH)_n-GBP-TPGS-NPs inhibiting MHCC97H cells is achieved by up-regulating the expression of Caspase-3, Caspase-8 and Caspase-9.

Jiaqi Huang, Howard N Hodis, Stephanie J Weinstein, Wendy J Mack, Joshua N Sampson, Alison M Mondul, Demetrius Albanes

Cancer Epidemiol Biomarkers Prev . 2020 Apr 20. doi: 10.1158/1055-9965.EPI-20-0187.

Abstract

Background: Vitamin E is an essential micronutrient and critical human antioxidant previously tested for cancer preventative effects with conflicting clinical trial results that have yet to be explained biologically.

Methods: We examined baseline and on-trial serum samples for 154 men randomly assigned to receive 400 IU vitamin E (as alpha-tocopheryl acetate; ATA) or placebo daily in the Vitamin E Atherosclerosis Prevention Study (VEAPS), and for 100 men administered 50 IU ATA or placebo daily in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC). Over 970 metabolites were identified using ultrahigh-performance LC/MS-MS. Linear regression models estimated the change in serum metabolites of men supplemented with vitamin E versus those receiving placebo in VEAPS as compared with ATBC.

Results: Serum alpha-carboxyethyl hydrochroman (CEHC) sulfate, alpha-tocopherol, and beta/gamma-tocopherol were significantly altered by ATA supplementation in both trials (all P values ≤5.1 × 10^-5, the Bonferroni multiple comparisons corrected statistical threshold). Serum C₂₂ lactone sulfate was significantly decreased in response to the high-dose vitamin E in VEAPS (β = -0.70, P = 8.1 × 10^-6), but not altered by the low dose in ATBC (β = -0.17, P = 0.4). In addition, changes in androgenic steroid metabolites were strongly correlated with the vitamin E supplement-associated change in C₂₂ lactone sulfate only in the VEAPS trial.

Conclusions: We found evidence of a dose-dependent vitamin E supplementation effect on a novel C₂₂ lactone sulfate compound that was correlated with several androgenic steroids.

Impact: Our data add information on a differential hormonal response based on vitamin E dose that could have direct relevance to opposing prostate cancer incidence results from previous large controlled trials.

Bruna Romana-Souza, Welker Silva-Xavier, Andréa Monte-Alto-Costa

J Cosmet Dermatol . 2020 Apr 19. doi: 10.1111/jocd.13413.

Abstract

Background: Aqueous formulations of vitamin C stabilized by vitamin E and ferulic acid at low pH effectively protect skin against reactive oxygen species-induced damage. However, the effects of these formulations on human skin have not clearly been described. The aim of this study was to investigate whether topical application of two commercially available formulations of vitamin C alter human skin using an ex vivo model.

Methods: Human skin explants were topically treated on alternate days with commercially available formulation 1 (15% vitamin C) at 100% (without dilution), 50%, or 10% diluted in saline or formulation 2 (20% vitamin C) at 100% (without dilution), 50%, or 10% diluted in saline. Only saline was applied to control skin explants.

Results: Topical formulation 1 at 100%, 50%, or 10%, but not formulation 2 at 100%, 50%, or 10%, reduced the viability of ex vivo human skin compared to the control after 7, 10, and 13 days. In addition, compared to the control, ex vivo human skin treated with formulation 1 at 50%, but not formulation 2 at 50%, also decreased mRNA levels of actin and ribosomal protein L10 and gene expression of extracellular matrix components after 10 days. Furthermore, after 10 days, topical application of formulation 1 at 50%, but not formulation 2 at 50%, decreased the protein expression of proliferating cellular nuclear antigen, lysyl oxidase, β-actin, and glyceraldehyde-3-phosphate dehydrogenase compared to the control.

Conclusions: Topical formulation 1, but not formulation 2, may reduce the viability of and protein synthesis in ex vivo human skin. Those effects might be due to action of vehicle of formulation 1 on ex vivo human skin.

Eric John Visser, Peter D Drummond, Julia L A Lee-Visser

Pain Pract . 2020 Apr 19. doi: 10.1111/papr.12902.

Abstract

Objective: To investigate the preventive effects of a combined antioxidant drug (N-acetylcysteine, vitamin E, and vitamin C [NEC]) on migraine outcomes. Migraine is characterized by increased oxidative stress and neurogenic inflammation in the brain; therefore, antioxidants may have a migraine preventive effect.

Design: Randomized, double-blind, sham-controlled pilot study.

Setting: Australian community.

Subjects: Adults reporting 2 to 8 migraines per month for at least a year.

Methods: After a 1-month baseline period, 35 subjects completed 3 months of treatment with NEC (n = 19) or sham (n = 16) capsules. The primary outcome was the difference in mean number of headaches per month between baseline and final month of the trial for NEC and sham groups; secondary outcomes are listed below.

Results: For NEC there was a significant decrease in mean number of headaches by 3.0 per month (P = 0.004) compared with 1.4 for sham (P = 0.073); there was no significant difference in these changes between the 2 groups (P = 0.052). Average monthly headache (P = 0.041) and migraine frequency (P = 0.018) were significantly less for NEC vs. sham. In NEC subjects, there was a significant decrease in average monthly migraine days (-3.1), moderate/severe headache days (-3.2), migraine duration, headache pain scores, and acute headache medication use.

Conclusions: This is the first randomized controlled trial to find that combined antioxidant therapy with NEC reduces headaches and migraines in adult migraineurs. Given the limitations of this pilot study, an adequately powered randomized controlled trial is planned to further investigate antioxidant prophylaxis in migraine.

Dazhe James Cao, Kim Aldy, Stephanie Hsu, Molly McGetrick, Guido Verbeck, Imesha De Silva, Sing-Yi Feng

J Med Toxicol . 2020 Apr 16. doi: 10.1007/s13181-020-00772-w.

Abstract

Electronic cigarettes (e-cigarettes) are battery-operated devices to insufflate nicotine or other psychoactive e-liquid aerosols. Despite initial claims of e-cigarettes as a nicotine-cessation device, aggressive marketing of e-cigarettes has led to an explosion in adolescents’ and young adults’ use over the last few years. Coupled with a lack of adequate investigation and regulation of e-cigarettes, the USA is facing an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) starting in mid-2019. While little long-term health hazard data are available, the components and constituents of e-cigarettes may adversely impact health. Propylene glycol and glycerin are humectants (water-retaining excipients) that generate pulmonary irritants and carcinogenic carbonyl compounds (e.g., formaldehyde, acetaldehyde, and acrolein) when heated in e-cigarettes. Metals contained in heating coils and cartridge casings may leach metals such as aluminum, chromium, iron, lead, manganese, nickel, and tin. Flavoring agents are considered safe for ingestion but lack safety data for inhalational exposures. Diacetyl, a common buttery flavoring agent, has known pulmonary toxicity with inhalational exposures leading to bronchiolitis obliterans. In 2019, clusters of lung injury associated with e-cigarette use were identified in Wisconsin and Illinois. Patients with EVALI present with a constellation of respiratory, gastrointestinal, and constitutional symptoms. Radiographically, patients have bilateral ground glass opacifications. As of February 18, 2020, the Centers for Disease Control has identified 2807 hospitalized patients diagnosed with either “confirmed” or “probable” EVALI in the US. Currently, vitamin E acetate (VEA) used as a diluent in tetrahydrocannabinol vape cartridges is implicated in EVALI. VEA cuts tetrahydrocannabinol oil without changing the appearance or viscosity. When inhaled, pulmonary tissue lacks the mechanism to metabolize and absorb VEA, which may lead to its accumulation. While most EVALI patients were hospitalized, treatment remains largely supportive, and use of corticosteroids has been associated with clinical improvement. The outbreak of EVALI highlights the need for regulation of e-cigarette devices and e-liquids. Clinicians need to be aware of the health hazards of e-cigarettes and be vigilant in asking about vaping.