Tocotrienol-rich fraction from annatto ameliorates expression of lysyl oxidase in human osteoblastic MG-63 cells

Kohno K, Yamada W, Ishitsuka A, Sekine M, Virgona N, Ota M, Yano T

Biosci Biotechnol Biochem. 2020 Mar;84(3):526-535. doi: 10.1080/09168451.2019.1693252. Epub 2019 Nov 19.

Abstract

Lysyl oxidase (LOX) is required for the formation of bone collagen cross-links. Inactivation of the LOX gene in osteoblasts by DNA methylation and JAK signaling has been reported to cause loss of cross-links and an increased risk of fractures. Tocotrienols (T3s) have proven benefits on bone strength, but their potential effects on LOX remain largely unknown. Thus, the present study investigates the in vitro effects of T3s on LOX expression in human osteoblastic MG-63 cells. Results indicated that Tocotrienol-Rich Fraction (TRF), the δ-T3 rich oil extracted from Annatto was the most effective and significantly increased LOX expression. TRF treatment decreased de-novo methyltransferases (DNMTs), DNMT3A and DNMT3B levels. In addition, TRF significantly inhibited JAK2 activation and decreased expression of Fli1, a transcription factor of DNMTs. We conclude that TRF induced an increase in LOX expression via inhibition of de-novo methylation and reduction of Fli1 expression by the inactivation of JAK2.

Eser Faki H, Tras B, Uney K

Mitochondrion. 2020 Feb 28;52:83-88. doi: 10.1016/j.mito.2020.02.011. [Epub ahead of print]

Abstract

To determine the effects of alpha lipoic acid (ALA) and vitamin E (Vit E) on mitochondrial dysfunction caused by statins. A total of 38 Wistar Albino rats were used in this study. The control group received dimethyl sulfoxide. The atorvastatin (A) group received atorvastatin (10 mg/kg). The A + ALA group received atorvastatin (10 mg/kg) and ALA (100 mg/kg). The A + Vit E group was administered atorvastatin (10 mg/kg) and Vit E (100 mg/kg). The A + ALA + Vit E group was administered atorvastatin (10 mg/kg), ALA (100 mg/kg) and Vit E (100 mg/kg). All applications were administered simultaneously by gavage for 20 days. ATP level and complex I activity were measured from liver, muscle, heart, kidney and brain. Atorvastatin significantly decreased the ATP levels in heart and kidney, while a slight decrease was seen in liver, muscle and brain. Atorvastatin caused an insignificant decrease in the complex I activity in all tissues examined. ALA administration significantly improved the ATP levels in the liver, heart and kidney, while Vit E improved the ATP levels in all tissues except the muscle compared to Atorvastatin group. Single administration of both ALA and vit E ameliorated complex I activity in the muscle, heart, kidney and brain. The combination of ALA and Vit E significantly improved the ATP levels in the liver, heart, kidney and brain and also provided significant improvements the complex I activity in all tissues. The undesirable effects of Atorvastatin on mitochondrial functions in this study ameliorated by using ALA and/or Vit E alone and in combination.

van Erp JHJ, Massier JRA, Halma JJ, Snijders TE, de Gast A

Acta Orthop. 2020 Feb 26:1-6. doi: 10.1080/17453674.2020.1730073. [Epub ahead of print]

Abstract

Background and purpose – The long-term survival of arthroplasty components may be limited by polyethylene wear-related problems such as periprosthetic osteolysis and aseptic loosening. Highly cross-linked polyethylene (HXLPE) blended with vitamin E was introduced to improve oxidative stability and to avoid long-term embrittlement. This study clinically compares the tribological behavior and clinical outcome of vitamin E blended HXLPE with ultra-high molecular weight polyethylene (UHMWPE) in an isoelastic monoblock cup for uncemented total hip arthroplasty.Patients and methods – In this randomized controlled trial (RCT), 199 patients were included: 102 patients received the vitamin E blended HXLPE cup, 97 patients the UHMWPE cup. Clinical and radiographic parameters were obtained preoperatively, directly postoperative and at 3, 12, and 24 months. Wear rates were compared using the mean linear femoral head penetration (FHP) rate.Results – 188 patients (94%) completed the 2-year follow-up. Mean patient satisfaction was higher in the vitamin E blended HXLPE group (8.9 [1]) than in in the control group (8.5 [2], p = 0.03). The Harris Hip Score (HHS) was higher in the vitamin E blended HXLPE group (95 [8]) than in the control group (92 [11], p = 0.3). The FHP rate was lower in the vitamin E blended HXLPE group: 0.046 mm/year compared with 0.056 mm/year in the control group (p = 0.05). No adverse reactions associated with the clinical application of vitamin E blended HXLPE were observed during follow-up, with an excellent 2-year survival to revision rate of 98% for both cups.Interpretation – This study shows the superior performance of the HXLPE blended with vitamin E acetabular cup with lower linear femoral head penetration rates and better clinical results compared with the UHMWPE acetabular cup after 2 years.

Minter BE, Lowes DA, Webster NR, Galley HF

Antioxidants (Basel). 2020 Feb 26;9(3). pii: E195. doi: 10.3390/antiox9030195.

Abstract

Sepsis is a life-threatening response to infection associated with inflammation, oxidative stress and mitochondrial dysfunction. We investigated differential effects of three forms of vitamin E, which accumulate in different cellular compartments, on oxidative stress, mitochondrial function, mRNA and protein expression profiles associated with the human Toll-like receptor (TLR) -2 and -4 pathways. Human endothelial cells were exposed to lipopolysaccharide (LPS)/peptidoglycan G (PepG) to mimic sepsis, MitoVitE, α-tocopherol, or Trolox. Oxidative stress, mitochondrial function, mitochondrial membrane potential and metabolic activity were measured. NFκB-P65, total and phosphorylated inhibitor of NFκB alpha (NFκBIA), and STAT-3 in nuclear extracts, interleukin (IL)-6 and IL-8 production in culture supernatants and cellular mRNA expression of 32 genes involved in Toll-like receptor-2 and -4 pathways were measured. Exposure to LPS/PepG caused increased total radical production (p = 0.022), decreased glutathione ratio (p = 0.016), reduced membrane potential and metabolic activity (both p < 0.0001), increased nuclear NFκB-P65 expression (p = 0.016) and increased IL-6/8 secretion (both p < 0.0001). MitoVitE, α- tocopherol and Trolox were similar in reducing oxidative stress, NFκB activation and interleukin secretion. MitoVitE had widespread downregulatory effects on gene expression. Despite differences in site of actions, all forms of vitamin E were protective under conditions mimicking sepsis. These results challenge the concept that protection inside mitochondria provides better protection.

Seo MH, Eo MY, Myoung H, Kim SM, Lee JH

J Korean Assoc Oral Maxillofac Surg. 2020 Feb;46(1):19-27. doi: 10.5125/jkaoms.2020.46.1.19. Epub 2020 Feb 26.

Abstract

OBJECTIVES:

Pentoxifylline (PTX) is a methylxanthine derivative that has been implicated in the pathogenesis of peripheral vessel disease and intermittent lameness. The purpose of this study was to investigate the effect of PTX and tocopherol in patients diagnosed with osteoradionecrosis (ORN), bisphosphonate-related osteonecrosis of the jaw (BRONJ), and chronic osteomyelitis using digital panoramic radiographs.

MATERIALS AND METHODS:

This study was performed in 25 patients who were prescribed PTX and tocopherol for treatment of ORN, BRONJ, and chronic osteomyelitis between January 2014 and May 2018 in Seoul National University Dental Hospital. Radiographic densities of the dental panorama were compared prior to starting PTX and tocopherol, at 3 months, and at 6 months after prescription. Radiographic densities were measured using Adobe Photoshop CS6 (Adobe System Inc., USA). Blood sample tests showing the degree of inflammation at the initial visit were considered the baseline and compared with results after 3 to 6 months. Statistical analysis was performed using the Mann-Whitney test and repeated measurement ANOVA using IBM SPSS 23.0 (IBM Corp., USA).

RESULTS:

Eight patients were diagnosed with ORN, nine patients with BRONJ, and the other 8 patients with chronic osteomyelitis. Ten of the 25 patients were men, average age was 66.32±14.39 years, and average duration of medication was 151.8±80.65 days (range, 56-315 days). Statistically significant increases were observed in the changes between 3 and 6 months after prescription (P<0.05). There was no significant difference between ORN, BRONJ, and chronic osteomyelitis. Only erythrocyte sedimentation rate (ESR) was statistically significantly lower than before treatment (P<0.05) among the white blood cell (WBC), ESR, and absolute neutrophil count (ANC).

CONCLUSION:

Long-term use of PTX and tocopherol can be an auxiliary method in the treatment of ORN, BRONJ, or chronic osteomyelitis in jaw.

Sotomayor CG, Minović I, Eggersdorfer ML, Riphagen IJ, de Borst MH, Dekker LH, Nolte IM, Frank J, van Zon SKR, Reijneveld SA, van der Molen JC, Vos MJ, Kootstra-Ros JE, Rodrigo R, Kema IP, Navis GJ, Bakker SJL

Nutrients. 2020 Feb 23;12(2). pii: E580. doi: 10.3390/nu12020580.

Abstract

Whether the affinity of serum vitamin E with total lipids hampers the appropriate assessment of its association with age-related risk factors has not been investigated in epidemiological studies. We aimed to compare linear regression-derived coefficients of the association of non-indexed and total lipids-indexed vitamin E isoforms with clinical and laboratory characteristics pertaining to the lipid, metabolic syndrome, and one-carbon metabolism biological domains. We studied 1429 elderly subjects (non-vitamin supplement users, 60-75 years old, with low and high socioeconomic status) from the population-based LifeLines Cohort and Biobank Study. We found that the associations of tocopherol isoforms with lipids were inverted in total lipids-indexed analyses, which may be indicative of overcorrection. Irrespective of the methods of standardization, we consistently found positive associations of α-tocopherol with vitamins of the one-carbon metabolism pathway and inverse associations with characteristics related to glucose metabolism. The associations of γ-tocopherol were often opposite to those of α-tocopherol. These data suggest that tocopherol isoforms and one-carbon metabolism are related, with beneficial and adverse associations for α-tocopherol and γ-tocopherol, respectively. Whether tocopherol isoforms, or their interplay, truly affect the one-carbon metabolism pathway remains to be further studied.

Mazdak H, Tolou Ghamari Z, Gholampour M

Int Urol Nephrol. 2020 Feb 22. doi: 10.1007/s11255-020-02411-3. [Epub ahead of print]

Abstract

PURPOSE:

Free radicals play an important role in the different complex course of carcinogenesis. Higher concentrations of reactive oxygen species are highly associated with the presence of tumors. The urinary bladder organ is also a target for many carcinogens. The major objective of this investigation was to measure the role of redox state or total antioxidant capacity (T-AOC) and antioxidant functions of vitamin E in patients with low-grade papillary cancer of the bladder (BC).

METHODS:

The blood sample was used for measurement of the T-AOC by the Trolox-TAC assay kit. Thirty-five patients with BC and thirty-five healthy subjects that matched for age were entered in this study. The obtained data were analyzed using the Statistical Package (SPSS Inc, Chicago, IL, USA). The significance level was set at p ≤ 0.05.

RESULTS:

In healthy controls, the mean ± SD for T-AOC was 91.8 ± 16.6 (U/ml), that was significantly higher when compared to the mean value of 24.5 ± 28.9 (U/ml) in patients with BC (p = 0.00). The difference in concentration of T-AOC before and after prescription of vitamin E was encountered with a p value of 0.16.

CONCLUSIONS:

By reference to the significant difference between T-AOC in patients and healthy controls, our results strongly suggest a low level of T-AOC in patients with BC. The obtained changes in T-AOC before and after management with vitamin E recommended additional consideration associates with different stages and grade of tumor in patients with BC.

Vineetha RC, Hariharan S, Jaleel A, Chandran M, Nair RH

Front Oncol. 2020 Feb 21;10:65. doi: 10.3389/fonc.2020.00065. eCollection 2020.

Abstract

Chemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (As₂O₃) treatment, which may be possible through the use of dietary supplements in combination. The present investigation evaluates the synergistic mechanism of action of vitamins, such as L-ascorbic acid (L-AA) and α-tocopherol (α-TOC) in As₂O₃ chemotherapy using human leukemia (HL-60) cells. In vitro assays on the cytotoxicity of As₂O₃ and vitamins and cellular apoptotic evidences were done; a proteomic investigation with mass spectrometry was also performed. The combination of L-AA and α-TOC potentiates As₂O₃ cytotoxicity in HL-60 cells, substantiated by depletion in antioxidant status, mitochondrial transmembrane potential, and inhibition of nuclear factor erythroid 2-related factor 2 and B-cell lymphoma 2 transcription factors. Mass spectrometry results showed decreased expression of proteins regulating cell cycle and translation in cells treated with As₂O₃, L-AA, and α-TOC when compared with As₂O₃-treated sample. In addition, this combination treatment identified numerous proteins associated with apoptosis and cell stress. HL-60 cells became more prone to As₂O₃ on exposure to L-AA and α-TOC, indicating that this combination may be a promising approach to increase the outcome of As₂O₃ chemotherapy.

Mason SA, Trewin AJ, Parker L, Wadley GD

Redox Biol. 2020 Feb 20:101471. doi: 10.1016/j.redox.2020.101471. [Epub ahead of print]

Abstract

Antioxidant supplements are commonly consumed by endurance athletes to minimize exercise-induced oxidative stress, with the intention of enhancing recovery and improving performance. There are numerous commercially available nutritional supplements that are targeted to athletes and health enthusiasts that allegedly possess antioxidant properties. However, most of these compounds are poorly investigated with respect to their in vivo redox activity and efficacy in humans. Therefore, this review will firstly provide a background to endurance exercise-related redox signalling and the subsequent adaptations in skeletal muscle and vascular function. The review will then discuss commonly available compounds with purported antioxidant effects for use by athletes. N-acetyl cysteine may be of benefit over the days prior to an endurance event; while chronic intake of combined 1000 mg vitamin C + vitamin E is not recommended during periods of heavy training associated with adaptations in skeletal muscle. Melatonin, vitamin E and α-lipoic acid appear effective at decreasing markers of exercise-induced oxidative stress. However, evidence on their effects on endurance performance are either lacking or not supportive. Catechins, anthocyanins, coenzyme Q10 and vitamin C may improve vascular function, however, evidence is either limited to specific sub-populations and/or does not translate to improved performance. Finally, additional research should clarify the potential benefits of curcumin in improving muscle recovery post intensive exercise; and the potential hampering effects of astaxanthin, selenium and vitamin A on skeletal muscle adaptations to endurance training. Overall, we highlight the lack of supportive evidence for most antioxidant compounds to recommend to athletes.