Interaction between and impact of IL-6 genotype and alpha-tocopherol levels on periodontal condition in aging individuals

Akihiro Yoshihara, Noboru Kaneko, Akane Miyamoto, Kaname Nohno

J Periodontal Res . 2020 Sep 20. doi: 10.1111/jre.12802. Online ahead of print.

Abstract

Background and objectives: Few studies have assessed the possible interaction between and impact of IL-6 variants and serum α-tocopherol levels on periodontal condition in older individuals. Here, we assessed the relationship between IL-6 variants and serum α-tocopherol levels on periodontal condition by considering effect modification.

Material and methods: Among the study participants, 359 who were 71 years of age underwent a dental examination, biochemical analysis, and interview. After dividing the participants into tertiles based on serum α-tocopherol levels, we conducted Poisson regression analysis to compare the prevalence rate ratio (PRR) for periodontal disease markers with the IL-6 genotype (rs1800796) based on each tertile adjusted by the number of teeth present (offset).

Results: The PRRs of the IL-6 genotype for periodontal condition (probing pocket depth [PPD], clinical attachment level [CAL], and bleeding on probing [BOP]) which were adjusted by the number of teeth present (offset) were 1.17 (P < .001), 1.37 (P < .001), and 1.08 (P = .048), respectively. In addition, a significant association was found between the reciprocal number of PRRs of the IL-6 genotype and three serum α-tocopherol levels. The adjusted PRRs (± standard error) of the IL-6 genotypes for PPD were 0.48 (0.12) for the first group (P < .001), 1.54 (0.04) for the second group (P < .001), and 2.11 (0.03) for the third group (P < .001); similar tendencies were seen for CAL and BOP.

Conclusion: The results of this study suggest a potential association between the IL-6 genotype and periodontal condition in relation to serum antioxidant concentrations.

Rafael Correia Cavalcante, Guilherme Tomasetti

J Craniomaxillofac Surg . 2020 Sep 18;S1010-5182(20)30206-7. doi: 10.1016/j.jcms.2020.09.008. Online ahead of print.

Abstract

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) is a previously described debilitating condition in which patients experience progressive bone destruction in the maxilla and/or mandible after exposure to certain drugs. Clinical management of MRONJ remains controversial, with no established guidelines. The aim of our study was to conduct a literature review on the effectiveness of pentoxifylline (PTX) and tocopherol (PENTO protocol) on MRONJ.

Study design: A literature review was conducted, using two different scientific databases, to evaluate the effects of PTX and tocopherol on MRONJ.

Discussion: PENTO protocol prescription to treat MRONJ was reported to be well tolerated, with minimal side-effects, and non-expensive when compared with other non-surgical treatment modalities. It was shown to relieve painful symptoms in all patients, and significant new bone formation was observed at final follow-up.

Conclusion: Observational and case-series studies have demonstrated that pentoxifylline and tocopherol are potentially useful in the non-surgical management of MRONJ.

Victoria L Wyckelsma, Tomas Venckunas, Marius Brazaitis, Stefano Gastaldello, Audrius Snieckus, Nerijus Eimantas, Neringa Baranauskiene, Andrejus Subocius, Albertas Skurvydas, Mati Pääsuke, Helena Gapeyeva, Priit Kaasik, Reedik Pääsuke, Jaak Jürimäe, Brigitte A Graf, Bengt Kayser, Nicolas Place, Daniel C Andersson, Sigitas Kamandulis, Håkan Westerblad

Antioxidants (Basel) . 2020 Sep 17;9(9):E879. doi: 10.3390/antiox9090879.

Abstract

Sprint interval training (SIT) has emerged as a time-efficient training regimen for young individuals. Here, we studied whether SIT is effective also in elderly individuals and whether the training response was affected by treatment with the antioxidants vitamin C and E. Recreationally active elderly (mean age 65) men received either vitamin C (1 g/day) and vitamin E (235 mg/day) or placebo. Training consisted of nine SIT sessions (three sessions/week for three weeks of 4-6 repetitions of 30-s all-out cycling sprints) interposed by 4 min rest. Vastus lateralis muscle biopsies were taken before, 1 h after, and 24 h after the first and last SIT sessions. At the end of the three weeks of training, SIT-induced changes in relative mRNA expression of reactive oxygen/nitrogen species (ROS)- and mitochondria-related proteins, inflammatory mediators, and the sarcoplasmic reticulum Ca²⁺ channel, the ryanodine receptor 1 (RyR1), were blunted in the vitamin treated group. Western blots frequently showed a major (>50%) decrease in the full-length expression of RyR1 24 h after SIT sessions; in the trained state, vitamin treatment seemed to provide protection against this severe RyR1 modification. Power at exhaustion during an incremental cycling test was increased by ~5% at the end of the training period, whereas maximal oxygen uptake remained unchanged; vitamin treatment did not affect these measures. In conclusion, treatment with the antioxidants vitamin C and E blunts SIT-induced cellular signaling in skeletal muscle of elderly individuals, while the present training regimen was too short or too intense for the changes in signaling to be translated into a clear-cut change in physical performance.

Hadeel K M Alboaklah, David S Leake

Free Radic Res . 2020 Sep 16;1-11. doi: 10.1080/10715762.2020.1817912. Online ahead of print.

Abstract

Many cholesterol-laden foam cells in atherosclerotic lesions are macrophages and much of their cholesterol is present in their lysosomes and derived from low density lipoprotein (LDL). LDL oxidation has been proposed to be involved in the pathogenesis of atherosclerosis. We have shown previously that LDL can be oxidised in the lysosomes of macrophages. α-Tocopherol has been shown to inhibit LDL oxidation in vitro, but did not protect against cardiovascular disease in large clinical trials. We have therefore investigated the effect of α-tocopherol on LDL oxidation at lysosomal pH (about pH 4.5). LDL was enriched with α-tocopherol by incubating human plasma with α-tocopherol followed by LDL isolation by ultracentrifugation. The α-tocopherol content of LDL was increased from 14.4 ± 0.2 to 24.3 ± 0.3 nmol/mg protein. LDL oxidation was assessed by measuring the formation of conjugated dienes at 234 nm and oxidised lipids (cholesteryl linoleate hydroperoxide and 7-ketocholesterol) by HPLC. As expected, LDL enriched with α-tocopherol was oxidised more slowly than control LDL by Cu²⁺ at pH 7.4, but was not protected against oxidation by Cu²⁺ or Fe³⁺ or a low concentration of Fe²⁺ at pH 4.5 (it was sometimes oxidised faster by α-tocopherol with Cu²⁺ or Fe³⁺ at pH 4.5). α-Tocopherol-enriched LDL reduced Cu²⁺ and Fe³⁺ into the more pro-oxidant Cu⁺ and Fe²⁺ faster than did control LDL at pH 4.5. These findings might help to explain why the large clinical trials of α-tocopherol did not protect against cardiovascular disease.

Justin S Rhodes, Catarina Rendeiro, Jonathan G Mun, Kristy Du, Pragya Thaman, Amanda Snyder, Heinrich Pinardo, Jenny Drnevich, Sriram Chandrasekaran, Chron-Si Lai, Karen J Schimpf, Matthew J Kuchan

J Nutr . 2020 Sep 16;nxaa249. doi: 10.1093/jn/nxaa249. Online ahead of print.

Abstract

Background: Alpha-tocopherol (αT), the bioactive constituent of vitamin E, is essential for fertility and neurological development. Synthetic αT (8 stereoisomers; all rac-αT) is added to infant formula at higher concentrations than natural αT (RRR-αT only) to adjust for bio-potency differences, but its effects on brain development are poorly understood.

Objectives: The objective was to determine the impact of bio-potency-adjusted dietary all rac-αT versus RRR-αT, fed to dams, on the hippocampal gene expression in weanling mice.

Methods: Male/female pairs of C57BL/6J mice were fed AIN 93-G containing RRR-αT (NAT) or all rac-αT (SYN) at 37.5 or 75 IU/kg (n = 10/group) throughout gestation and lactation. Male pups were euthanized at 21 days. Half the brain was evaluated for the αT concentration and stereoisomer distribution. The hippocampus was dissected from the other half, and RNA was extracted and sequenced. Milk αT was analyzed in separate dams.

Results: A total of 797 differentially expressed genes (DEGs) were identified in the hippocampi across the 4 dietary groups, at a false discovery rate of 10%. Comparing the NAT-37.5 group to the NAT-75 group or the SYN-37.5 group to the SYN-75 group, small differences in brain αT concentrations (10%; P < 0.05) led to subtle changes (<10%) in gene expression of 600 (NAT) or 487 genes (SYN), which were statistically significant. Marked differences in brain αT stereoisomer profiles (P < 0.0001) had a small effect on fewer genes (NAT-37.5 vs. SYN-37.5, 179; NAT-75 vs. SYN-75, 182). Most of the DEGs were involved in transcription regulation and synapse formation. A network analysis constructed around known vitamin E interacting proteins (VIPs) revealed a group of 32 DEGs between NAT-37.5 vs. SYN-37.5, explained by expression of the gene for the VIP, protein kinase C zeta (Pkcz).

Conclusions: In weanling mouse hippocampi, a network of genes involved in transcription regulation and synapse formation was differentially affected by dam diet αT concentration and source: all rac-αT or RRR-αT.

Abbas Sadeghi, Farah Farokhi, Ali Shalizar-Jalali, Gholamreza Najafi

Vet Res Forum . Summer 2020;11(3):257-263. doi: 10.30466/vrf.2019.91184.2206. Epub 2020 Sep 15.

Abstract

Polyvinyl chloride (PVC) has toxic effects through the induction of oxidative stress in the body and testicles. Vitamin E (Vit E) is a dietary compound that functions as an antioxidant scavenging toxic free radicals. The present study aimed to probe the protective effect of Vit E against PVC-induced reprotoxicity in male rats. In this experimental study, 24 male rats were randomly divided into four groups (n=6) including control, Vit E (150 mg kg^-1 per day; orally), PVC (1000 mg kg^-1 per day; orally) and PVC + Vit E. After 40 days, rats were euthanized and epididymal sperms characteristics, embryo development and malondialdehyde (MDA) and testosterone levels were examined. The PVC decreased sperm count, motility and viability as well as testosterone level and increased sperms with damaged chromatin in comparison with controls. Also, the percentages of fertilization, two-cell embryos and blastocysts as well as MDA levels were decreased in PVC-treated rats. However, Vit E improved PVC-induced alterations in aforesaid parameters. The results indicated that PVC can reduce fertility potential in male rats probably through androgen and sperm quality and quantity reductions, while Vit E can exert protective effects in PVC-related reproductive toxicities.

Lavinia Casati, Francesca Pagani, Roberto Maggi, Francesco Ferrucci, Valeria Sibilia

Int J Mol Sci . 2020 Sep 12;21(18):E6675. doi: 10.3390/ijms21186675.

Dear Editor,

We have carefully read the Letter to the Editor by Pang and Chin related to our paper entitled “Food for bone: evidence for a role for delta-tocotrienol in the physiological control of osteoblast migration” [1] published in the International Journal of Molecular Science.

We have some issues regarding the points raised by the authors.

The paper from Shen and colleagues 2018 [2] clearly shows the effect of dietary supplementation of tocotrienol in the suppression of bone resorption, probably mediated by the reduction of oxidative stress. Our statement “osteoporosis has been correlated with low intake, and serum levels of TTs” refers to this paper. We disagree with the authors that “dietary tocotrienol level has not been shown to correlate with bone health, probably due to the absence of a reliable dietary questionnaire that could assess the tocotrienol intake”, since Shen and colleagues (2018) have reported that a 12 week annatto-derived tocotrienol supplementation, previously used to examine the effects of tocotrienol on bone turnover, resulted in a significant increase in serum delta-tocotrienol levels in postmenopausal osteoporotic women [2].

Kok-Lun Pang, Kok-Yong Chin

Int J Mol Sci . 2020 Sep 12;21(18):E6674. doi: 10.3390/ijms21186674.

Dear Editor,

We applaud the innovative work by Casati et al., which explored the effects of delta-tocotrienol (δ-TT) in promoting osteoblast migration [1]. Vitamin E is reported as a nutrient important for maintaining bone health in epidemiological studies [2]. However, the statement “osteoporosis has been correlated with low intake, and serum levels of TTs” is inaccurate because dietary tocotrienol level has not been shown to correlate with bone health, probably due to the absence of a reliable dietary questionnaire that could assess the tocotrienol intake. Nevertheless, there is an abundance of preclinical evidence on the beneficial skeletal effects of tocotrienol. Most in vitro studies focus on the differentiation of osteoblasts, while the animal studies used bone cellular histomorphometry to quantify the bone cells in osteopenic rats treated with tocotrienol [3,4]. The work by Casati et al. is the first that focuses on the influence of tocotrienol on osteoblast migration, which plays an essential role in fracture healing. More accurately, mesenchymal stem cells migrated to the fracture site during fibrovascular phase and callus formation will differentiate into osteoblasts and perform bone formation [5]. A previous study also showed that particles incorporated with annatto tocotrienol rich in δ-TT could enhance callus strength of male rats with long bone fracture fixed with plate and screws [6]. The finding of δ-TT enhances the transcriptional activities of β-catenin also echoes our previous study, which demonstrated that annatto tocotrienol supplementation (60 mg/kg/day for 2 months) increased beta-catenin gene expression in the bone of orchidectomized rats [7].

Kazuo Mukai, Yasuhiro Maruoka, Saya Kitagaki, Shin-Ichi Nagaoka

J Oleo Sci . 2020 Sep 10. doi: 10.5650/jos.ess20091. Online ahead of print.

Abstract

Measurements of aroxyl (ArO・)-radical-scavenging rate constants (k_s^AOH) of antioxidants (AOHs) (i.e., α-, β-, γ-, δ-Tocopherol (TocH) and ubiquinol-10 (UQ₁₀H₂)) were performed in ethanol/chloroform/H₂O (50/50/1, v/v) solution, using stopped-flow spectrophotometry. k_s^AOH values were measured not only for each AOH, but also for the mixtures of two AOHs (i.e., TocH and UQ₁₀H₂). k_s^TocH values for α-, β-, γ-, δ-TocH increased 1.21, 1.28, 1.55, and 1.19 times, respectively, under the coexistence of constant concentrations of UQ₁₀H₂. Similar measurements were performed for eight vegetable oils 1 – 8, containing different concentrations of α-, β-, γ-, δ-tocopherol (TocH) and -tocotrienol (Toc-3H). k_s^Oil values of all eight vegetable oils 1 – 8 also increased 1.24 – 1.54 times under the coexistence of constant concentrations of UQ₁₀H₂. A new mechanism to explain the notable increase of k_s^AOH values under the coexistence of two kinds of phenolic AOHs was proposed. UV-vis absorption of α-, β-, γ-Toc · radicals, produced by reaction of α-, β-, γ-TocHs (or vegetable oils 1 – 8) with ArO ·, disappeared under the coexistence of TocHs (or oils) and UQ₁₀H₂, suggesting that the prooxidant reaction resulting from the presence of Toc · radicals is suppressed in the presence of UQ₁₀H₂.

Maren C Podszun, Joon-Yong Chung, Kris Ylaya, David E Kleiner, Stephen M Hewitt, Yaron Rotman

J Histochem Cytochem . 2020 Sep;68(9):635-643. doi: 10.1369/0022155420946402.

Abstract

Lipid peroxidation is a common feature of liver diseases, especially non-alcoholic fatty liver disease (NAFLD). There are limited validated tools to study intra-hepatic lipid peroxidation, especially for small specimen. We developed a semi-quantitative, fully automated immunohistochemistry assay for the detection of 4-hydroxynoneal (4-HNE) protein adducts, a marker of lipid peroxidation, for adaptation to clinical diagnostics and research. We used Hep G2 cells treated with 4-HNE to validate specificity, sensitivity, and dynamic range of the antibody. Staining and semi-quantitative automated readout were confirmed in human needle-biopsy liver samples from subjects with NAFLD and normal liver histology. The ability to detect changes in lipid peroxidation was tested in paired liver biopsies from NAFLD subjects, obtained before and after 4 weeks of treatment with the antioxidant vitamin E (ClinicalTrials.gov NCT01792115, n=21). The cellular calibrator was linear and NAFLD patients had significantly higher levels of 4-HNE adducts compared to controls (p=0.02). Vitamin E treatment significantly decreased 4-HNE (p=0.0002). Our findings demonstrate that 4-HNE quantification by immunohistochemistry and automated image analysis is feasible and able to detect changes in hepatic lipid peroxidation in clinical trials. This method can be applied to archival and fresh samples and should be considered for use in assessing NAFLD histology.