The effect of tocopheryl phosphates (TPM) on the development of atherosclerosis in apolipoprotein-e deficient mice.

Libinaki R, Vinh A, Tesanovic-Klajic S, Widdop RE, Gaspari TA.

Clin Exp Pharmacol Physiol. 2017 Jul 26. doi: 10.1111/1440-1681.12821. [Epub ahead of print]

Abstract

α-Tocopheryl phosphate (TP) is a naturally occurring form of Vitamin E found in the body. In the present study we compared the ability of an α-TP mixture (TPM) against a standard Vitamin E supplement, α-tocopherol acetate (TA) on the development of atherosclerotic lesions in ApoE-deficient mice. Mice were maintained on either a normal chow diet for 24 weeks (Normal Diet), versus a group in which the final 8 weeks of the 24 week period mice were placed on a high fat (21%), high cholesterol (0.15%) challenge diet (HFHC), to exacerbate atherosclerotic lesion development.. The difference in these two control groups established the extent of the diet induced atherosclerotic lesion development. Mice in the various treatment groups received either TA (300mg/kg chow) or TPM (6.7 to 200mg/kg chow) for 24 weeks, with TPM treatment resulting in dose-dependent significant reductions in atherosclerotic lesion formation and plasma levels of pro-inflammatory cytokines. TA-treated mice, with the tocopherol equivalent TPM dose (200mg/kg chow), showed no significant reduction in plasma lipid levels or evidence for aortic lesion regression. At this TPM equivalent TA dose, a 44% reduction in aortic lesion formation was observed. In addition, these TPM treated mice, also showed a marked reduction in aortic superoxide formation and decreased circulating plasma levels of known pro-inflammatory markers IL-6, MCP-1, IL-1β, IFN-γ and TNF-α. These findings indicate that TPM treatment slows progression of atherosclerotic lesions in ApoE-deficient mice with this effect potentially involving reduced oxidative stress and decreased inflammation.

Burbank AJ, Duran CG, Pan Y, Burns P, Jones S, Jiang Q, Yang C, Jenkins S, Wells H, Alexis N, Kesimer M, Bennett WD, Zhou H, Peden DB, Hernandez ML.

J Allergy Clin Immunol. 2017 Jul 20. pii: S0091-6749(17)31110-7. doi: 10.1016/j.jaci.2017.06.029. [Epub ahead of print]

Abstract

BACKGROUND:

We and others have shown that the gamma tocopherol (γT) isoform of vitamin E has multiple anti-inflammatory and antioxidant actions and that γT supplementation reduces eosinophilic and endotoxin (LPS)-induced neutrophilic airway inflammation in animal models and healthy human volunteers.

OBJECTIVE:

To determine if γT supplementation reduces eosinophilic airway inflammation and acute neutrophilic response to inhaled LPS challenge in volunteers with asthma.

METHODS:

Participants with mild asthma were enrolled in a double-blinded, placebo controlled crossover study to assess the effect of 1200 mg of γT daily for 14 days on sputum eosinophils, mucins and cytokines. We also assessed the effect on acute inflammatory response to inhaled LPS challenge following γT treatment, focusing on changes in sputum neutrophilia, mucins and cytokines. Mucociliary clearance was measured using gamma scintigraphy.

RESULTS:

Fifteen subjects with mild asthma completed both arms of the study. Compared to placebo, γT notably reduced pre-LPS challenge sputum eosinophils and mucins, including MUC5AC, and reduced LPS-induced airway neutrophil recruitment 6 and 24-hours after challenge. Mucociliary clearance was slowed 4-hours post-challenge in the placebo group but not in the γT treatment group. Total sputum mucins (but not MUC5AC) were reduced at 24-hours post-challenge during γT treatment compared to placebo.

CONCLUSION:

γT supplementation for 14 days reduced inflammatory features of asthma, including sputum eosinophils and mucins, as well as acute airway response to inhaled LPS challenge when compared to placebo. Larger scale clinical trials are needed to assess the efficacy of γT supplements as a complementary or steroid-sparing treatment for asthma.

Jung H, Chen CO, Blumberg JB, Kwak HK.

Eur J Nutr. 2017 Jul 10. doi: 10.1007/s00394-017-1480-5. [Epub ahead of print]

Abstract

PURPOSE:

Almonds have shown to beneficially modify some cardiovascular risk factors in clinical trials conducted in diverse ethnic populations but this relationship has never been tested in Koreans. Thus, we tested the impact of almonds consumed as a snack within the context of a typical Korean diet on cardiovascular risk factors.

METHODS:

We conducted a randomized, crossover trial in a free-living setting with a 2-week run-in period, two 4-week intervention phases, and a 2-week washout period between interventions. Eighty four overweight/obese participants (11 M/73 F; 52.4 ± 0.6 year; 25.4 ± 0.22 kg/m²) consumed either 56 g of almonds or isocaloric cookies daily for 4 weeks.

RESULTS:

Mean % daily energy intake at baseline was 64.8, 21.3, and 14.9% from carbohydrate, fat, and protein, respectively. The addition of 56 g of almonds daily decreased carbohydrate energy to 55.0%, increased fat to 32.0%, and maintained protein at 14.7%. Consuming the almonds increased intake of MUFA by 192.3%, PUFA by 84.5%, vitamin E by 102.7%, and dietary fiber by 11.8% and decreased % energy from carbohydrate by 14.1%. Total caloric intake was increased by the almonds, but body weight, waist circumference, and body composition were not affected. Almonds in overweight and obese Korean adults decreased TC, LDL-C, and non-HDL-C by 5.5, 4.6, and 6.4%, respectively, compared to the cookie control (P ≤ 0.05). Almonds increased plasma α-tocopherol by 8.5% (P ≤ 0.05) from the baseline and tended to increase its value as compared to cookies (P = 0.055). Neither the almonds nor cookies altered plasma protein carbonyls, MDA or oxLDL. Of serum inflammatory markers, IL-10 was decreased by almond intake (P ≤ 0.05), and ICAM-1, IL-1β, and IL-6 tended to be lower with almonds, compared to the cookies.

CONCLUSIONS:

Almonds at 56 g/day consumed as a snack favorably modified the Korean diet by increasing MUFA, PUFA, vitamin E, and dietary fiber intake and decreasing % energy intake from carbohydrate. Almonds also enhanced plasma α-tocopherol status and serum TC and LDL-C in overweight and obese Koreans. Thus, including almonds in typical Korean diets as a snack can help healthy overweight/obese individuals improve nutritional status and reduce their risk for CVD.

Selim A, Khalaf MM, Gad AM, Abd El-Raouf OM.

J Biochem Mol Toxicol. 2017 Jul 6. doi: 10.1002/jbt.21957. [Epub ahead of print]

Abstract

Amikacin (AMIK) is an aminoglycoside antibiotic that possesses considerable nephrotoxic adverse effects. This study examined the protective effects of vitamin E (VIT. E) or rosuvastatin (ROSU) against AMIK-induced nephrotoxicity. For this purpose, eight groups of rats were used. Two control groups received saline and vehicle, AMIK group (1.2 g/kg, i.p.), VIT. E group (1000 mg/kg; p.o.), ROSU group (10 mg/kg; p.o.), AMIK + VIT. E group, AMIK + ROSU group, and combination group. The results showed that AMIK significantly increased serum levels of urea and creatinine. Meanwhile, serum levels of total protein and albumin were decreased. The kidney content of malondialdehyde was increased, whereas glutathione content and catalase activity were decreased. Tumor necrosis factor-α and nuclear transcriptional factor levels were increased. Conversely, administration of VIT. E and/or ROSU with AMIK ameliorated such damage and reduced DNA fragmentation, apoptosis, and necrosis. In conclusion, co-administration of VIT. E, ROSU, or their combination alleviated AMIK-induced nephrotoxicity.

Xun C, Mamat M, Guo H, Mamati P, Sheng J, Zhang J, Xu T, Liang W, Cao R, Sheng W.

Exp Ther Med. 2017 Jul;14(1):431-438. doi: 10.3892/etm.2017.4505. Epub 2017 May 23.

Abstract

In recent years accumulating evidence has indicated that tocotrienol exhibits an oxidation resistance function, decreased cholesterol function, inhibits cancer function and has unique physiological functions, including anti-inflammatory, anti-apoptotic and anti-oxidative properties. The present study investigated the effect of tocotrienols on spinal cord injury (SCI) by evaluating oxidative stress, inflammation and inducible nitric oxide synthase (iNOS) in rats. A rat model of SCI was induced by operation. SCI rats were treated with 120 mg/kg/day tocotrienol once a day for eight consecutive weeks. Functional recovery following SCI was measured by using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Then the volume of spinal cord contusions was measured following induction of SCI in the rats. In SCI rats, serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, nuclear factor-κB p65 unit, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 levels were analyzed using respective commercial immunoassay kits. Firstly, iNOS, transforming growth factor (TGF)-β, collagen type IV and fibronectin protein expression levels, in addition to iNOS activity and plasma nitric oxide (NO) production in SCI rats was analyzed using western blot analysis, commercial kits and Griess reagent, respectively. Tocotrienol treatment elevated BBB scores and contused volume in the SCI rats. Tocotrienol protected against SCI with reduced oxidative stress and inflammation, and inhibited iNOS protein expression iNOS activity and plasma NO production in rats. In addition, treatment with tocotrienols suppressed TGF-β, collagen type IV and fibronectin protein expression levels in SCI rats. These results suggest that tocotrienols protect SCI, and suppress oxidative stress, inflammation and iNOS in this model of SCI through TGF-β, collagen type IV and fibronectin signaling pathways.

Tantavisut S, Tanavalee A, Honsawek S, Suantawee T, Ngarmukos S, Adisakwatana S, Callaghan JJ.

BMC Musculoskelet Disord. 2017 Jun 29;18(1):281. doi: 10.1186/s12891-017-1637-7.

Abstract

BACKGROUND:

This study was performed to evaluate the antioxidative and anti-inflammatory effects of vitamin E on oxidative stress in the plasma, synovial fluid, and synovial tissue of patients with knee osteoarthritis.

METHODS:

Seventy-two patients with late-stage knee osteoarthritis scheduled for total knee arthroplasty were randomized to take oral placebo (Group A) or 400 IU of vitamin E (Group B) once a day for 2 months before undergoing surgery. The blood levels of endpoints indicating oxidative stress or antioxidant capacity, Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC), and adverse effects were compared before and after the intervention between the two groups. At surgery, these redox endpoints and histological findings were compared between the synovial fluid and synovial tissue.

RESULTS:

In blood samples, the pre-intervention of oxidative stress and antioxidative capacity were not different between Group A and Group B. In post-intervention blood samples, the Malondialdehyde (Group A 1.34 ± 0.10, Group B 1.00 ± 0.09, p < 0.02), Alpha tocopherol(Group A 15.92 ± 1.08, Group B 24.65 ± 1.47, p < 0.01) and Trolox equivalent antioxidant capacity (Group A 4.22 ± 0.10, Group B 5.04 ± 0.10, 0 < 0.01) were significantly different between Group A and Group B. In synovial fluid samples, the Malondialdehyde (Group A 1.42 ± 0.12, Group B 1.06 ± 1.08, p 0.01), Alphatocopherol (Group A 4.51, Group B 7.03, p < 0.01), Trolox equivalent antioxidant capacity (Group A, 1.89 ± 0.06, Group B 2.19 ± 0.10) were significantly different between Group A and Group B. The pre-intervention WOMAC score and KSS score were not different between Group A and Group B. The post-intervention WOMAC score was significantly improved in all categories in Group B (Pain: Group A 27.26 ± 0.89, Group B 19.19 ± 1.43, p < 0.01; Stiffness: Group A 8.23 ± 0.79, Group B 5.45 ± 0.73, p 0.01; Function: Group A 94.77 ± 4.22, Group B 72.74 ± 6.55, p < 0.01). The post-intervention KSS score was significantly improved in all categories in Group B (Clinical: Group A 25.31 ± 14.33, Group B 33.52 ± 16.96, p < 0.01; Functional: Group A 41.43 ± 16.11, Group B 51.61 ± 19.60, p 0.02). Significantly fewer synovial tissue cells were stained with nitrotyrosine and hematoxylin-eosin in Group B than in Group A. There were no differences in adverse effects or surgical complications between the groups.

CONCLUSION:

Vitamin E is an effective antioxidant that can improve clinical symptoms and reduce oxidative stress conditions in patients with late-stage knee osteoarthritis.

Azzi A.

Mol Aspects Med. 2017 Jun 17. pii: S0098-2997(17)30041-9. doi: 10.1016/j.mam.2017.06.004. [Epub ahead of print]

Abstract

Four tocopherols are available in nature and are absorbed with the diet, but only one RRR-α-tocopherol satisfies the criteria of being a vitamin. The biological activity of the different tocopherols studied in the rat by the resorption-gestation test has been inconsistently extrapolated to human beings where the tocopherols have no influence on a successful pregnancy. Diminution of RRR-α-tocopherol intake results in diseases characterized by ataxia, whose pathogenetic mechanism, despite vigorous claims, has not been clarified. The calculation of the Daily Reference Intake (DRI), necessary to prevent disease, is based on an obsolete test, the peroxide-induced erythrocyte hemolysis, called the gold standard, but of highly questioned validity. If many epidemiological studies have given positive results, showing prevention by high vitamin E containing diets of cardiovascular events, neurodegenerative disease, macular degeneration and cancer, the clinical confirmatory intervention studies were mostly negative. On the positive side, besides preventing vitamin E deficiency diseases, vitamin E has shown efficacy as anti-inflammatory and immune boosting compound. It has also shown some efficacy in protecting against nonalcoholic hepato-steatosis. At a molecular level, vitamin E and some of its metabolites have shown capacity of regulating cell signaling and modulating gene transcription.

Del Carmen Baez M, Tarán M, de La Paz Scribano M, Balceda A, Buonanotte C, Blencio S, Fonseca I, Moya M.

Antiinflamm Antiallergy Agents Med Chem. 2017 Jun 16. doi: 10.2174/1871523016666170616121133. [Epub ahead of print]

Abstract

The oxidative process in atherogenesis generated by proinflammatory induction and response to antioxidants vitamins in an experimental model were analyzed.

METHODS:

Male rats were used: (A)Control, (B)Control+vitamin E plus C, (C)Hyperfibrinogenemia and (D)Hyperfibrinogenemia+vitamins E plus C. Hyperfibrinogenemia induced by daily injection of adrenaline (0.1mg/day/rat) for 120 days.

TREATMENT:

3.42 mg/kg of vitamin E plus 2.14 mg/kg of vitamin C, fifteen days after induction. Vascular histology analyzed by optical microscopy. Fibrinogen, nitrites and superoxide dismutase(SOD) analyzed by spectrophotometry.

STATISTICS:

MANOVA, Hotelling test for post testing, significance level p<0.05.

RESULTS:

(C) group showed higher fibrinogen than (A) and (B)(p<0.001). Compared to (C) group, (D) showed a decrease of fibrinogen(p<0.001). A marked increase in nitrites was found in (C) versus (A), (B) and (D) groups(p<0.001). SOD activity increased in (C) group compared to groups (A) and (B) (p<0.001). In the group (D) an increase of the activity of this enzyme was observed in comparison to groups (C)(p<0.001), (A) and (B) (p<0.0001 in both). The (C) group shown endothelial denudation, thickening of the vascular intima and extracellular matrix enlargement with foam cells(p<0.001).

CONCLUSION:

These results strongly suggest that vitamins E plus C produce regression of inflammatory and oxidative stress processes in this experimental model.

Tang HY, Ho HY, Chiu DT, Huang CY, Cheng ML, Chen CM

Clin Chim Acta. 2017 May 2;470:75-80. doi: 10.1016/j.cca.2017.05.001. [Epub ahead of print]

Abstract

BACKGROUND:

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy resulting in demyelination in peripheral nervous system. Myelin enriched in lipids is easily oxidized by reactive oxygen species during inflammation. Oxidative stress and lipophilic anti-oxidative capacities in GBS patients have not been fully explored. To evaluate the redox status of GBS patients, we measured malondialdehyde (MDA), myeloperoxidase (MPO), lipophilic antioxidants, and tocopherols concentrations in plasma from GBS patients and age-matched healthy controls.

RESULTS:

Concentrations of γ-tocopherol and δ-tocopherol decreased significantly, and α-carotene significantly increased in GBS patients compared to healthy controls. However, no significant changes in MDA and MPO concentrations were detected. In GBS patients, the γ-tocopherol concentration correlated positively with concentrations of δ-tocopherol, α-tocopherol, lutein, Q10, and γ-CEHC, respectively. Similarly, the δ-tocopherol concentration correlated positively with γ-tocopherol, α-tocopherol, lutein, Q10, δ-CEHC, and γ-CEHC concentrations, respectively. The receiver operating characteristics curve analysis showed that γ-tocopherol may serve as a good predictor for GBS.

CONCLUSIONS:

Diminished lipophilic antioxidant defense, mainly γ-tocopherol and δ-tocopherol, in GBS patients accounting for their lowered resistance to reactive oxygen species is probably associated with pathogenesis of GBS, and potentially useful for the development of therapeutic strategies.

Du X, Jiang S, Bo L, Liu J, Zeng X, Xie Y, He Q, Ye X, Song W, Zhao J.

Chemosphere. 2017 Apr;173:14-21. doi: 10.1016/j.chemosphere.2017.01.042. Epub 2017 Jan 8.

Abstract

This study aims to observe whether the combined treatment with vitamin E (vit E) and omega-3 polyunsaturated fatty acids (Ω-3 FA) could prevent the fine particulate matter (PM_2.5)-induced cardiovascular injury through alleviating inflammation and oxidative stress. At the same time, the appropriate combination dosage of vit E and Ω-3 FA was explored to find an optimized protective dose to protect the injury induced by PM_2.5. The SD rats were pretreated with different concentration of vit E and Ω-3 FA separately or jointly. Then the rats were exposed to ambient PM_2.5 by intratracheal instillation for three times. The expression of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) in serum and supernatant of cardiac tissue were detected by ELISA kits. The levels of malondialdehyde (MDA), superoxide Dismutase (SOD) and glutathione-peroxidase (GSH-Px) in myocardium and the level of MDA in serum were measured. Meanwhile, the cardiac injury was evaluated by histopathological examination. Compared with the severe injury of rats in PM_2.5 exposure group, the rats in vit E or Ω-3 FA-pretreated groups had a slighter injury in heart. Meanwhile, pretreatment with vit E or Ω-3 FA induced a significantly alleviation of the inflammatory cytokines (TNF-α, IL-1β, IL-6) and the elevation of the anti-oxidative activity especially in the rats pretreated with combined vit E and Ω-3 FA. In addition, the combined protecting effects of vit E and Ω-3 FA showed a dose-dependent manner. Supplementation with vit E and Ω-3 FA could protect the PM_2.5-induced injury, and the combination of vit E and Ω-3 FA might produce more effective effects than the separate nutrient did.