Vitamin E status and its determinants in patients with cystic fibrosis

Sapiejka E, Krzyżanowska-Jankowska P, Wenska-Chyży E, Szczepanik M, Walkowiak D, Cofta S, Pogorzelski A, Skorupa W, Walkowiak J

Adv Med Sci. 2018 Sep;63(2):341-346. doi: 10.1016/j.advms.2018.04.001. Epub 2018 Aug 3.

Abstract

PURPOSE:

The risk of vitamin E deficiency is of primary concern in cystic fibrosis patients. However, early diagnosis and routine vitamin Esupplementation can lead to its normal or even high levels. In the present study, we assessed vitamin E status in a large group of cystic fibrosis patients. Moreover, we also aimed to establish determinants of its body resources in cystic fibrosis patients.

MATERIAL AND METHODS:

The study group comprised 211 cystic fibrosis patients aged from 1 month to 48 years. In all of them serum α-tocopherol concentration was analyzed using high-performance liquid chromatography.

RESULTS:

Median vitamin E concentration was 9.9 μg/ml (1st-3rd quartile: 7.5-13.5). Vitamin E deficiency was found in 17 (8.0%) and high levels were documented in 24 (11.4%) participants. Patients with and without vitamin E deficiency did not differ significantly with respect to age, standardized body weight and height, FEV1, albumin concentration and vitamin E supplementation dose. However, vitamin E deficiency appeared more frequently in participants without vitamin E supplementation. Moreover, in multiple linear regression analysis pancreatic insufficiency, severe CFTR gene mutation and vitamin E dose, were potentially defined as determinants of vitamin E concentration.

CONCLUSIONS:

Vitamin E deficiency in cystic fibrosis patients is rather rare nowadays. Excessive vitamin E levels seem to be more frequent. Vitamin E status wasn’t documented to be strictly related to clinical determinants. Beyond vitamin E supplementation, exocrine pancreatic function and CFTR gene mutations may have had an impact on the vitamin E body resources in cystic fibrosis patients.

Irías-Mata A, Sus N, Flory S, Stock D, Woerner D, Podszun M, Frank J

Redox Biol. 2018 Aug 5;19:28-36. doi: 10.1016/j.redox.2018.07.027. [Epub ahead of print]

Abstract

Liver cells express a cytosolic α-tocopherol transfer protein (αTTP) with high binding affinity for α-tocopherol (αT) and much lower affinities for the non-αT congeners. The role of αTTP in the intracellular distribution of the different vitamin E forms is currently unknown. We therefore investigated the intracellular localization of αT, γ-tocopherol (γT), α-tocotrienol (αT3), and γ-tocotrienol (γT3) in cultured hepatic cells with and without stable expression of αTTP. We first determined cellular uptake of the four congeners and found the methylation of the chromanol ring and saturation of the sidechain to be important factors, with tocotrienols being taken up more efficiently than tocopherols and the γ-congeners more than the α-congeners, irrespective of the expression of αTTP. This, however, could perhaps also be due to an observed higher stability of tocotrienols, compared to tocopherols, in culture media rather than a higher absorption. We then incubated HepG2 cells and αTTP-expressing HepG2 cells with αT, γT, αT3, or γT3, isolated organelle fractions by density gradient centrifugation, and determined the concentrations of the congeners in the subcellular fractions. All four congeners were primarily associated with the lysosomes, endoplasmic reticulum, and plasma membrane, whereas only αT correlated with mitochondria. Neither the chromanol ring methylation or sidechain saturation, nor the expression of αTTP were important factors for the intracellular distribution of vitamin E. In conclusion, αTTP does not appear to regulate the uptake and intracellular localization of different vitamin E congeners in cultured liver cells.

Sapiejka E, Krzyżanowska-Jankowska P, Wenska-Chyży E, Szczepanik M, Walkowiak D, Cofta S, Pogorzelski A, Skorupa W, Walkowiak J

Adv Med Sci. 2018 Aug 3;63(2):341-346. doi: 10.1016/j.advms.2018.04.001. [Epub ahead of print]

Abstract

PURPOSE:

MATERIAL AND METHODS:

The study group comprised 211 cystic fibrosis patients aged from 1 month to 48 years. In all of them serum α-tocopherol concentration was analyzed using high-performance liquid chromatography.

RESULTS:

CONCLUSIONS:

Amraoui W, Adjabi N, Bououza F, Boumendjel M, Taibi F, Boumendjel A, Abdennour C, Messarah M

Toxicol Res. 2018 Jul;34(3):231-239. doi: 10.5487/TR.2018.34.3.231. Epub 2018 Jul 15.

Abstract

Bisphenol A, an everywhere chemical, is applied as a plasticizer in polycarbonate plastics, which often used in our everyday products and in epoxy resins as protective coatings and linings for food and beverage cans for decades. Human exposure to BPA may lead to adverse effects by interfering with oestrogen receptors. Our present study was conducted to investigate the protective effects of selenium (Se) and vitamin E(Vit E) on BPA-induced damage in the liver of male rats. Animals were randomly divided into four groups: the first group received olive oil and served as control. The second group received both (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet). The third one treated orally by (10 mg/kg b.w.) of BPA. The last group received (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet) concomitantly with (10 mg/kg b.w.) BPA. Exposure to BPA for three weeks engendered a hepatic disorder. An increased AST and ALT enzymatic activity was noticed in BPA-treated group as compared to other groups. Furthermore, a change in glucose, cholesterol, LDL-C, HDL-C, albumin, and bilirubin level was remarkable. Moreover, exposure to BPA increased malondialdehyde levels while reduced gluthatione content was decreased in the liver homogenate. A decrease in glutathione peroxidase, glutathione s-transferase and catalase activities was observed in the same group. Administration of selenium and vitamin E through the diet in BPA treated rats ameliorated the biochemical parameters cited above. In addition, an improvement in activities of liver enzymes was recorded. The histological findings confirmed the biochemical results. The model of this study that we employed characterized the relationships between BPA-induced hepatotoxicity and its alleviation by natural antioxidants like selenium and vitamin E.

Chalouati H, Ben Sâad MM, Payrastre L

Toxicol Mech Methods. 2018 Jul 31:1-31. doi: 10.1080/15376516.2018.1506847. [Epub ahead of print]

Abstract

The protective effects of α-Tocopherol (vitamin E) on liver injury induced by hexachlorobenzene (HCB) were investigated in adult male rats of Wistar strain. Animals were randomly divided into six groups of eight rats each. Group 1 and 2 have received HCB, dissolved in olive oil, at a dose of 4 mg or 16 mg/kg b.w, respectively. Group 3 and 4 were treated by the same doses of HCB (4 mg and 16 mg/kg b.w) after 1h of pretreatment with α-tocopherol at a dose of 100 mg kg^-1 b.w. The other two groups served as controls; which received either olive oil only, a solvent of HCB, or α-tocopherol. A significant increase in hepatic lipid peroxidation (LPO) and GSH activity were observed following HCB administration. The activities of antioxidant enzymes like superoxide dismutase and catalase were significantly decreased while glutathione peroxidase was significantly increased following HCB administration. Similarly, a significant increase in plasma levels of various marker enzymes [aminotransferase (AST and ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] and a decrease of total protein level were observed. Pretreatment with vitamin E of HCB treated rats ameliorated all biochemical parameters to near normal values. Liver histological study confirmed biochemical parameters and the beneficial role of vitamin E.

Okamura Y, Omori A, Asada N, Ono A

J Clin Biochem Nutr. 2018 Jul;63(1):50-57. doi: 10.3164/jcbn.17-96. Epub 2018 Apr 3.

Abstract

The purpose of this study was to investigate the influence of vitamins C and E on the toxic action of alcohol in rat liver regeneration. Male Sprague-Dawley rats subjected to 70% partial hepatectomy were divided into five groups (Groups 1 to 5). Rats in Groups 2 to 5 were only provided alcohol for drinking. Additionally, vitamin C, vitamin E, and vitamin C in combination with vitamin E were administered to Groups 3, 4, and 5, respectively. Alcohol inhibits liver regeneration, resulting in an increase in free radicals produced by alcohol metabolism and thus causing cellular damage and altering liver function. During liver regeneration, vitamins C and E significantly ameliorated liver injury from alcohol administration by reducing hepatic lipid peroxidation. Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus may be more effective in combination than either vitamin alone against alcohol-mediated toxic effects during liver regeneration.

Pervez MA, Khan DA, Ijaz A, Khan S.

Turk J Gastroenterol. 2018 Mar;29(2):170-176. doi: 10.5152/tjg.2018.17297.

Abstract

BACKGROUND/AIMS:

Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide and is associated with increased morbidity and mortality. Currently, there is no definitive treatment for this disease. δ-Tocotrienol has potent anti-inflammatory and antioxidant properties and may reduce liver injury in NAFLD. The present study aims to evaluate the efficacy and safety of δ-tocotrienol in the treatment of NAFLD.

MATERIALS AND METHODS:

The present study was a randomized, double-blind, placebo-controlled pilot study conducted in patients aged > 20 years, belonging to both sexes, having ultrasound-proven fatty liver disease, having a fatty liver index (FLI) of ≥ 60, and persistent elevation of alanine transaminase. A total of 71 patients were assigned to receive either oral δ-tocotrienol (n=35, 300 mg twice daily) or placebo (n=36) for 12 weeks. At the baseline and at the end of the study, clinical and biochemical parameters, including lipid profile, liver function tests, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured. Body mass index and FLI were calculated, and ultrasound grading of hepatic steatosis was performed.

RESULTS:

Out of 71 enrolled patients, 64 patients, 31 in the δ-tocotrienol group and 33 in the placebo group, completed the study. After 12 weeks of supplementation, δ-tocotrienol showed greater efficacy than placebo by decreasing serum aminotransferases, hs-CRP, MDA, and FLI score (p<0.001). However, it did not improve hepatic steatosis on ultrasound examination. No adverse effects were reported.

CONCLUSION:

δ-Tocotrienol was safe, and it effectively improved aminotransferase levels and inflammatory and oxidative stress markers in patients with NAFLD. Large-scale randomized clinical trials are warranted to further support these findings.

Zang S, Chen J, Song Y, Bai L, Chen J, Chi X, He F, Sheng H, Wang J, Xie S, Xie W, Yang Y, Zhang J, Zheng M, Zou Z, Wang B, Shi J

Adv Ther. 2018 Feb;35(2):218-231. doi: 10.1007/s12325-018-0670-8. Epub 2018 Feb 6.

Abstract

INTRODUCTION:

Vitamin E is one of the most promising agents for nonalcoholic steatohepatitis (NASH) treatment, and its drug responsiveness may be closely associated with haptoglobin (Hp) genotype. However, its efficacy and safety remain unknown in China. This clinical trial of vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholic steatohepatitis (VENS) is conducted to evaluate (a) the efficacy and safety of treatment with vitamin E softgel (300 mg/day) determined from standardized histologic scoring of liver biopsies, (b) whether treatment with vitamin E improves biochemical parameters, cytokines, anthropometric parameters, controlled attenuation parameter (CAP), and transient elastography (TE) values determined by Fibroscan and health-related quality of life (SF-36), (c) whether the efficacy of vitamin E treatment is associated with the Hp genotype in nondiabetic adults with NASH.

METHODS:

VENS is a multicenter, randomized, double-masked, placebo parallel controlled trial to evaluate the efficacy and safety of treatment with vitamin E softgel in nondiabetic adults with NASH versus treatment with placebo in China. Liver biopsies are read by a pathological evaluation committee independently according to the NASH Clinical Research Network (CRN) scoring system. The NAFLD activity score (NAS) represents the sum of scores for steatosis, lobular inflammation, and hepatocyte ballooning. The definition of histologic improvement requires all three of the following criteria to be met: (a) either improvement in NAS by at least 2 points or post-treatment NAS score no higher than 3, (b) at least 1-point improvement in the score for ballooning, and (c) no worsening of fibrosis stages. We plan to recruit 120 biopsy-proven NASH patients from13 centers in China. Participants will be randomly assigned to groups treated with either with vitamin E (100 mg, tid) or placebo for 96 weeks then followed by 24 weeks of post-treatment observation. Biochemical parameters, cytokines, anthropometric parameters, CAP and TE values, Hp genotype, and several questionnaires will be collected as per the schedule. This protocol was approved by the Ethics Committee of Hangzhou Normal University Affiliated Hospital to ensure patients safety, and R&G Pharmastudies Co., Ltd. was established for monitoring the accumulated interim data to review efficacy and quality of data collection and overall study management.

RESULTS:

As a preliminary study, a mobile phone application (app) for lifestyle modification and database recording ( http://laiyivens.365hy.com ) was exploited for every participant. The percentage of NAFLD patients with Hp 2-2 allele is much higher than that of Western patients (65.71% vs 36%, respectively), which suggests that the Chinese benefit more from vitamin E treatment.

CONCLUSION:

VENS is the first randomized controlled trial (RCT) to evaluate the efficacy of Vitamin E in treating nondiabetic NASH patients in China.

Abdel-Daim MM, Abdeen A

Food Chem Toxicol. 2018 Feb 9;114:69-77. doi: 10.1016/j.fct.2018.01.055. [Epub ahead of print]

Abstract

Fipronil (FPN) is a phenylpyrazole insecticide that is extensively used in agriculture and veterinary applications. However, FPN is also a potent environmental toxicant to animals and humans. Therefore, the current study aimed to investigate the protective role of rosuvastatin (ROSU) and vitamin E (Vit E) against FPN-induced hepatorenal toxicity in albino rats. Seven groups with eight rats each were used for this purpose; these groups included the control vehicle group that received corn oil, the Vit E group (1000 mg/kg, orally), the ROSU group (10 mg/kg, orally), the FPN group (20 mg/kg, orally), the FPN-ROSU group, the FPN-Vit E group, and the FPN-Vit E-ROSU group. The results revealed that FPN significantly increased serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, cholesterol, urea, and creatinine. In addition, there were substantial increases in the liver and kidney contents of malondialdehyde and nitric oxide, along with significant decreases in glutathione, superoxide dismutase, catalase, and glutathione peroxidase. FPN also caused histological changes and increased the expression of caspase-3 in the liver and kidney tissues. However, administration of ROSU and Vit E alone or in combination ameliorated the FPN-induced oxidative damage and apoptosis, possibly through their antioxidant properties.

El Hadi H, Vettor R, Rossato M

Antioxidants (Basel). 2018 Jan 16;7(1). pii: E12. doi: 10.3390/antiox7010012.

Abstract

Obesity is one of the major epidemics of this millennium, and its incidence is growing worldwide. Following the epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) has become a disease of increasing prevalence and a leading cause of morbidity and mortality closely related to cardiovascular disease, malignancies, and cirrhosis. It is believed that oxidative stress is a main player in the development and progression of NAFLD. Currently, a pharmacological approach has become necessary in NAFLD because of a failure to modify lifestyle and dietary habits in most patients. Vitamin E is a potent antioxidant that has been shown to reduce oxidative stress in NAFLD. This review summarizes the biological activities of vitamin E, with a primary focus on its therapeutic efficacy in NAFLD.