The effect of zinc and/or vitamin E supplementation on biochemical parameters of selenium-overdosed rats

Melčová M, Száková J, Mlejnek P, Zídek V, Fučíková A, Praus L, Zídková J, Mestek O, Kaňa A, Mikulík K, Tlustoš P

Pol J Vet Sci. 2018 Dec;21(4):731-740. doi: 10.24425/124312.

Abstract

The normotensive (Wistar) and spontaneously hypertensive (SHR) rats were examined to assess the response of the organism to selenium (Se) overdose. Moreover, the effect of zinc (Zn) and vitamin E, i.e. dietary components interacting in many biochemical processes with Se, on the Se uptake was evaluated. The control group was fed an untreated diet, and the diets of two other groups were overdosed with Se in the form of sodium selenite (9 mg/kg) and supplemented with Zn (13 mg/kg). Two experimental groups were fed a diet supplemented with Zn (13 mg/kg) and Se at an adequate level (0.009 mg/kg); a half of the animals was supplemented with vitamin E. The results showed significant differences in the Se contents between the rat strains in case of Se-overdosed groups, where in the liver and kidney tissue Se contents of SHR rats exceeded 3- and 7-fold the normotensive ones. The Se uptake was altered by the vitamin E; no effect of Zn was observed. Activities of antioxidant enzymes were determined in the animal tissues indicating different patterns according to rat strain, tissue analysed, and administered Se dose. Thus, Se overdose, for instance, via an incorrectly prepared dietary supplement, can result in serious imbalances of the biochemical status of the animals.

Polyzos SA, Kountouras J, Anastasilakis AD, Makras P, Hawa G, Sonnleitner L, Missbichler A, Doulberis M, Katsinelos P, Terpos E

Hormones (Athens). 2018 Dec;17(4):573-579. doi: 10.1007/s42000-018-0083-8. Epub 2018 Nov 22.

Abstract

AIM:

The evaluation of (a) noggin levels in patients with simple steatosis (SS) vs. nonalcoholic steatohepatitis (NASH) vs. controls, and (b) the effect of combined spironolactone plus vitamin E vs. vitamin E monotherapy on noggin levels in biopsy-proven patients with nonalcoholic fatty liver disease (NAFLD).

METHODS:

In the case-control study, 15 patients with SS, 16 with NASH, and 24 controls were included. In the randomized controlled trial, NAFLD patients were assigned to vitamin E (400 IU/d) or spironolactone (25 mg/d) plus vitamin E for 52 weeks.

RESULTS:

Noggin levels were lower in SS (5.8 ± 1.5 pmol/l) and NASH (8.7 ± 2.4 pmol/l) patients than in controls (13.7 ± 2.7 pmol/l; p for trend = 0.040), but were similar in SS and NASH patients. After adjustment for potential cofounders, log(noggin) remained different between groups. Log(noggin) levels similarly increased post-treatment in both groups: log(noggin) was not different between groups (p = 0.20), but increased within groups over time (p < 0.001), without a significant group × time interaction (p = 0.62). Log(noggin) significantly increased at month 2 post-treatment (p = 0.008 vs. baseline) and remained stable thereafter.

CONCLUSIONS:

Lower noggin levels were observed in NAFLD patients than in controls. Noggin levels increased similarly by either combined low-dose spironolactone plus vitamin E or vitamin E monotherapy.

Vilar-Gomez E, Vuppalanchi R, Gawrieh S, Ghabril M, Saxena R, Cummings OW, Chalasani N

Hepatology. 2018 Dec 1. doi: 10.1002/hep.30368. [Epub ahead of print]

Abstract

Vitamin E improves liver histology in non-diabetic adults with nonalcoholic steatohepatitis (NASH), but its impact on long-term patient outcomes is unknown. We evaluated whether vitamin E treatment improves clinical outcomes of NASH patients with bridging fibrosis or cirrhosis. Two hundred and thirty-six patients with biopsy-proven NASH and bridging fibrosis or cirrhosis seen at Indiana University Medical Center between October 2004, and January 2016 were included. Ninety of them took 800 IU/day of vitamin E for ≥ 2 years (vitamin E users) and were propensity matched to 90 adults who did not take vitamin E (controls) after adjusting for fibrosis severity, age, gender, body mass index, comorbidities and their treatment, LDL cholesterol, liver biochemistries and length of follow-up on vitamin E. Covariate-adjusted cox and competing risk regression models were assessed to evaluate association between vitamin E treatment and patient outcomes. The median follow-up was 5.62 (IQR: 4.3-7.5) and 5.6 (IQR: 4-6.9) years for vitamin E users and controls respectively. Vitamin E users had higher adjusted transplant-free survival (78% vs. 49%, P<.01) and lower rates of hepatic decompensation (37% vs. 62%, P=.04) than controls. After controlling for severity of fibrosis, calendar year of patient enrollment and other potential confounders, vitamin E treatment decreased the risk of death or transplant (adj. HR: 0.30, 95% CI: 0.12-0.74, P<.01) and hepatic decompensation (adj. sHR: 0.52, 95% CI: 0.28-0.96, P=.036). These benefits were evident in both diabetics as well as non-diabetics. Adjusted 10-year cumulative probability of HCC, vascular events and non-hepatic cancers were not different between vitamin E exposed and controls. CONCLUSION: vitamin E use was associated with improved clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis.

Torquato P, Bartolini D, Giusepponi D, Piroddi M, Sebastiani B, Saluti G, Galarini R, Galli F

Free Radic Biol Med. 2018 Nov 30;131:115-125. doi: 10.1016/j.freeradbiomed.2018.11.036. [Epub ahead of print]

Abstract

Lipid peroxidation is one of the earliest pathogenic events of non-alcoholic fatty liver disease (NAFLD). In this context, an increased oxidation of the lipoperoxyl radical scavenger α-tocopherol (α-TOH) should occur already in the subclinical phases of the disease to compensate for the increase oxidation of the lipid excess of liver and possibly of other tissues. However, this assumption remains unsupported by direct analytical evidence. In this study, GC-MS/MS and LC-MS/MS procedures have been developed and applied for the first time to measure the vitamin Eoxidation metabolite α-tocopheryl quinone (α-TQ) in plasma of fatty liver (FL) subjects that were compared in a pilot cross-sectional study with healthy controls. The protein adducts of 4-hydroxynonenal (4-HNE) and the free form of polyunsaturated free fatty acids (PUFA) were measured as surrogate indicators of lipid peroxidation. α-TQ formation was also investigated in human liver cells after supplementation with α-TOH and/or fatty acids (to induce steatosis). Compared with controls, FL subjects showed increased (absolute and α-TOH-corrected) levels of plasma α-TQ and 4-HNE, and decreased concentrations of PUFA. α-TQ levels positively correlated with indices of liver damage and metabolic dysfunction, such as alanine aminotransferase, bilirubin and triglycerides, and negatively correlated with HDL cholesterol. Fatty acid supplementation in human hepatocytes stimulated the generation of cellular oxidants and α-TOH uptake leading to increased α-TQ formation and secretion in the extracellular medium – both were markedly stimulated by α-TOH supplementation. In conclusion, plasma α-TQ represents an early biomarker of the lipoperoxyl radical-induced oxidation of vitamin E and lipotoxicity of the fatty liver.

Kim Y, Natarajan SK, Chung S

Mol Nutr Food Res. 2018 Nov;62(21):e1800519. doi: 10.1002/mnfr.201800519. Epub 2018 Sep 9.

Abstract

SCOPE:

Gamma-tocotrienol (γT3), an unsaturated isoform of vitamin E, is implicated in the hepatoprotective effects. The aim is to determine the effectiveness of γT3 on nonalcoholic fatty liver disease (NAFLD).

METHODS AND RESULTS:

C57BL/6 male mice are fed a diet containing high fat (45%) and cholesterol (0.2%) along with sucrose drink (HFCS) or HFCS diet supplemented with 0.1% γT3 (HFCS + γT3). The inclusion of γT3 robustly decreases the HFCS diet-induced de novo lipogenesis (DNL), ER stress, and inflammation leading to reduced hepatic steatosis and fibrosis. Next, mice are fed a methionine- and choline-deficient (MCD) diet or MCD diet with γT3 (MCD + γT3). The γT3 supplementation significantly reduces the MCD diet-induced hepatic ER stress and fibrosis despite the minimal impact on steatosis. To further investigate the role of ER stress, the mice with genetic ablation of CHOP are fed an MCD or MCD + γT3 diet. CHOP deletion abolishes the γT3-mediated suppression of hepatic fibrosis, suggesting that modulation of ER stress is a prerequisite to inhibit hepatic inflammation and fibrosis.

CONCLUSION:

γT3 supplementation is effective in attenuating NAFLD and fibrosis through a synergistic mechanism of decreased DNL and hepatic ER stress. This work strongly supports the translational potential of γT3 supplementation against NAFLD.

Sajjad S, Malik H, Saeed L, Hashim I, Farooq U, Manzoor F

Physiol Res. 2018 Oct 23. [Epub ahead of print]

Abstract

Current study evaluated the synergistic potential of propolis and Vitamin E against sublethal toxicity of aluminum chloride on different biochemical parameters and liver histology. Swiss albino mice (n=42) were randomly divided into five groups. Group I received 0.2 ml of 0.9 % saline solution, Group II received Propolis (50 mg/kg b.w.), Group III received Vitamin E (150 mg/kg b.w.), Group IV received AlCl3 50 mg/kg b.w., Group V received AlCl3 + Propolis, Group VI received AlCl3 + Vitamin E and Group VI received AlCl3 + propolis + Vitamin E. Blood and tissue samples were collected after 7 and 21 days. The body weight of the animals significantly increased in all groups except group IV. The concentration of serum high density lipoprotein significantly decreased in group IV and increased in group V, VI and VII. The level of aspartate aminotransferase, alanine transferase, alkaline phosphatase, triglycerides, total cholesterol, and low density lipoprotein significantly increased in AlCl3 treated group and increased in group V, VI and VII. Tissue sections were processed and stained by hematoxylin and eosin. Group II showed cellular necrosis. Group V, VI showed decreased number of vacuolization, sinusoidal spacing and macrophage cell infiltration. Group VI showed less degenerative changes in the third week. Vitamin E and propolis in combination with Al provides more protection against AlCl3 induced toxicity.

Chalouati H, Ben Sâad MM, Payrastre L

Toxicol Mech Methods. 2018 Oct 3:1-8. 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 1 h 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 (aspartate aminotransférase (AST) and alanine aminotransferase (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.

Mathews SE, Kumar RB, Shukla AP

Curr Opin Endocrinol Diabetes Obes. 2018 Oct;25(5):315-320. doi: 10.1097/MED.0000000000000432.

Abstract

PURPOSE OF REVIEW:

Obesity and nonalcoholic steatohepatitis (NASH) are epidemiologically and pathophysiologically linked disorders. Here, we summarize the effect of obesity on NASH and how it has a cascading effect on cardiovascular dysfunction. We also review the current and emerging treatment options for NASH.

RECENT FINDINGS:

The link between NASH and cardiac dysfunction has been further delineated in recent studies demonstrating endothelial dysfunction, diastolic dysfunction, and increased coronary artery calcification in patients with known NASH. Standard treatment of obesity with lifestyle interventions including diet, exercise, and behavioral modification has been shown to improve NASH as well as reduce cardiovascular dysfunction. In addition to FDA-approved drugs like vitamin E and pioglitazone, several agents including NGM282, obeticholic acid, elafibranor, and liraglutide are currently being investigated for their therapeutic potential in NASH. Recent studies show that bariatric surgery results in significant improvement or resolution of NASH.

SUMMARY:

Obesity is a major factor in the development of nonalcoholic fatty liver disease (NAFLD) and its progression to steatohepatitis. Patients with NAFLD have a significant increase in cardiovascular disease risk. For biopsy-proven NASH, vitamin E and pioglitazone are the recommended medical treatments in addition to lifestyle modification.

Perumpail BJ, Li AA, John N, Sallam S, Shah ND, Kwong W, Cholankeril G, Kim D, Ahmed A

Diseases. 2018 Sep 24;6(4). pii: E86. doi: 10.3390/diseases6040086

Abstract

There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

Tapia G, Silva D, Romero N, Pettinelli P, Dossi CG, de Miguel M, González-Mañán D

Nutrition. 2018 Sep;53:1-8. doi: 10.1016/j.nut.2018.01.012. Epub 2018 Apr 3.

Abstract

OBJECTIVE:

The aim of this study was to evaluate the contribution of tocopherols present in Rosa mosqueta oil (RM) in the prevention of high-fat diet (HFD)-induced alterations.

METHODS:

Male C57 BL/6 J mice (n = 9/group) were fed for 12 wk and divided into four groups: control (CD; 10% kcal fat, 20% kcal protein, 70% kcal carbohydrates); HFD (60% as fat, 20% kcal protein, 20% kcal carbohydrates); HFD + RM (0.01 mL/g body weight/d); and HFD + RM^– without tocopherols (0.01 mL/g body weight/d). Parameters of obesity, liver steatosis (histology, triacylglycerols content), inflammation (adipose NLRP3 inflammasome, tumor necrosis factor-α and interleukin-1 β expression, hepatic nuclear factor-κB) and oxidative stress (hepatic Nrf2 activation, carbonylated proteins) were evaluated.

RESULTS:

Liver steatosis, inflammatory, and oxidative stress parameters were significantly (P < 0.05) increased in the HFD + RM^– compared with the HFD + RM, with no differences between HFD and HFD + RM^–.

CONCLUSION:

The present study suggests that α- and γ-tocopherols from RM may have an important role in the prevention of alterations induced by HFD.