Efficacy of Vitamin E in Methotrexate-Induced Hepatotoxicity in Rheumatoid Arthritis: An Open-Label Case-Control Study

Binit Vaidya, Manisha Bhochhibhoya, Shweta Nakarmi

Int J Rheumatol . 2020 May 1;2020:5723485. doi: 10.1155/2020/5723485.

Abstract

Objective: To examine the efficacy of vitamin E in methotrexate- (MTX-) induced transaminitis in patients with rheumatoid arthritis (RA).

Methods: A case-control study was conducted at a tertiary rheumatology center for 12 months. Patients with RA on MTX and deranged aminotransferases were included. Patients with previous liver diseases, baseline transaminitis before methotrexate initiation, alcohol intake, muscle diseases, under hepatotoxic drugs, and aminotransferases > 3 times the upper normal limit were excluded. The patients were divided into treatment (vitamin E 400 mg bid for 3 months) and control groups (no vitamin E) using a random number table. The dose of MTX was unaltered. Follow-up was done after 3 and 6 months. Independent t-test was done to compare means of two groups. Paired t-test was done to compare differences in mean.

Results: Among 230 patients, 86.5% were female with a mean BMI of 25.9 ± 4.5 kg/m². In the treatment group, SGPT and SGOT at baseline were 73.1 ± 20.4 and 60.2 ± 24.5 IU/L, respectively; at 3-month follow-up 44.6 ± 34.2 and 38.3 ± 20.8 IU/L, respectively; and at 6-month follow-up 40.4 ± 35.7 and 34.2 ± 21.9 IU/L, respectively. In the control group, SGPT and SGOT at baseline were 63.4 ± 15.1 and 46.8 ± 13.7 IU/L, respectively, and at 3-month follow-up 55.8 ± 45.9 and 45.5 ± 30.9 IU/L, respectively. Significant decrease in the level of aminotransferases was seen in the treatment group (p value < 0.001) and not in the control group (p values 0.161 and 0.728, respectively). The change in levels of SGPT and SGOT from baseline to 3 months of follow-up was statistically significant in between two study groups (p values 0.007 and <0.001, respectively). From the control group, 29 patients were crossed over to vitamin E for the next 3 months. SGPT and SGOT decreased from 97.6 ± 44.1 to 46.1 ± 40.9 and 69.3 ± 34.9 to 29.1 ± 11.6 IU/L, respectively (p values 0.031 and 0.017, respectively).

Delanian SE, Lenglet T, Maisonobe T, Resche-Rigon M, Pradat PF

Int J Radiat Oncol Biol Phys. 2020 May 1;107(1):154-162. doi: 10.1016/j.ijrobp.2020.01.002. Epub 2020 Jan 24.

Abstract

PURPOSE:

Radiation-induced (RI) plexopathy is a rare peripheral nerve injury after radiation therapy for cancer. No treatment has been shown to slow its progression. A pentoxifylline-vitamin E combination significantly reduced RI fibrosis, and its association with clodronate (PENTOCLO) allowed healing of osteoradionecrosis and reduction of neurologic symptoms in phase 2 trials.

METHODS AND MATERIALS:

A placebo-controlled, double-blind trial conducted in adults with RI limb plexopathy without cancer recurrence, randomized in 2 arms to PENTOCLO (pentoxifylline 800 mg, tocopherol 1000 mg, clodronate 1600 mg 5 days per week) or triple placebo. The primary outcome measure after 18 months of treatment was the neurologic Subjective Objective Management Analytic (SOMA) score evaluating pain, paresthesia, and motor disability.

RESULTS:

Between 2011 and 2015, 59 patients were included: 1 false inclusion (neoplastic plexopathy), 29 treated with placebo (group P), and 29 treated with the active drugs (group A); 46 patients presented an upper-limb and 12 a lower-limb plexopathy. The mean delay after irradiation was 26 ± 8 years, for patients with neurologic symptoms for 5 ± 5 years. The median global SOMA scores in the P and A groups, respectively, were 9 (range, 6-11) versus 9 (range, 8-11) at M₀ and 9 (range, 5-12) versus 10 (range, 6-11) at M₁₈ without any significant difference. Analysis of the secondary outcomes showed that SOMA score subdomains for pain and paresthesia were more affected in group A (not significant). The frequency of adverse events was similar in the 2 groups (81% of patients): slight expected vascular-gastrointestinal symptoms in A, but a large excess of RI complications (arterial stenosis).

CONCLUSIONS:

This first randomized drug trial in RI plexopathy failed to show a beneficial effect. More studies are needed in patients with less advanced disease and fewer confounding comorbidities and with a more sensitive measure to detect a therapeutic effect.

Praça FG, Viegas JSR, Peh HY, Garbin TN, Medina WSG, Bentley MVLB

Mater Sci Eng C Mater Biol Appl. 2020 May;110:110639. doi: 10.1016/j.msec.2020.110639. Epub 2020 Jan 7.

Abstract

In this study, we developed a water-in-oil microemulsion containing vitamin A (retinol) and vitamin E (α-tocopherol), which serves as a multifunctional nanosystem that co-delivers antioxidants and displayed additive effect against acute skin inflammation. Microemulsion (ME) was prepared by mixing a surfactant blend (Tween 80 and propylene glycol, 5:1) with isopropyl myristate and water (ratio of 50:40:10, respectively). Vitamin A (0.05% w/w concentration) and/or vitamin E (0.1% w/w concentration) were incorporated into the surfactant mixture of ME by stirring with a magnetic stirrer for 30 min. This multifunctional ME displayed physical stability, with low cytotoxicity in 3T3 cell line, as well as cellular internalization into the cytosol. In vivo treatments using ME delivering α-tocopherol reduced dermal expression of TNF-α by 1.3-fold (p < 0.01), when compared to unloaded ME treatment group. When retinol was added into the ME containing α-tocopherol, it further reduced TNF-α expression by 2-fold (p < 0.001), suggesting the additive effect of vitamin E and vitamin A in the treatment against skin inflammation. In conclusion, we successfully developed the use of water-in-oil ME to pack both vitamin E and vitamin A, and demonstrated for the first time its anti-inflammatory potential when applied topically to TPA-induced inflamed skin.

Thais P Leandrin, Cristiane M Alencar, Keli R Victorino, Andréa Ar Dantas, Reinaldo O Lima, Júlia C Martins, Joissi F Zaniboni, Edson A de Campos, Milton C Kuga

J Contemp Dent Pract . 2020 May 1;21(5):481-485.

Abstract

Aim: To evaluate the effect of two antioxidant formulations (sodium ascorbate and α-tocopherol) on fracture resistance of endodontically treated teeth.

Materials and methods: Sixty human premolars were endodontically treated and divided into six groups (n = 10): G1 (negative control)-unbleached and restored with composite resin; G2 (positive control)-bleached in three sessions, using hydrogen peroxide (15 H₂O₂) plus titanium dioxide (TiO₂) nanoparticles, photoactivated by LED laser system and restored with composite resin; G3-bleaching similar to G2, after the use of 10% sodium ascorbate gel for 24 hours and restored with composite resin; G4-similar to G3, but with the use of 10% sodium ascorbate solution and restored with composite resin; G5 and G6-similar to G3, but with the use of 10% α-tocopherol in alcohol or carbopol, respectively, and was also restored. A mechanical fracture resistance test was performed and the Kruskal-Wallis test was used to evaluate the results (α = 0.05).

Results: No statistical difference was observed in fracture resistance between groups (p > 0.05). Regarding the antioxidant and pharmaceutical formulation applied, no statistical difference was detected in any comparison (p > 0.05). The frequency of fractures considered favorable was higher in G1 and G3 compared to the other groups.

Conclusion: The endodontically treated teeth bleached with 15 H₂O₂ plus TiO₂ nanoparticles and photoactivated with the LED laser did not decrease the fracture resistance and the use of sodium ascorbate or α-tocopherol did not increase the crown fracture resistance.

Zeynep Erdemli, Mehmet Erman Erdemli, Yusuf Turkoz, Birgul Yigitcan, Mehmet Arif Aladag, Yilmaz Cigremis, Rumeyza Hilal Cırık, Eyup Altinoz, Harika Gozukara Bag

Biotech Histochem . 2020 Apr 29;1-9. doi: 10.1080/10520295.2020.1751880.

Abstract

We investigated the effects of acrylamide (AA) and vitamin E treatment during pregnancy on brain tissues of fetuses and on adult rats. Pregnant rats were divided into five groups: control, corn oil, vitamin E, AA, vitamin E +AA. The rats administered AA received10 mg/kg/day and those administered vitamin E received 100 mg/kg/day both by via oral gavage for 20 days. On day 20 of pregnancy, half of the pregnant rats were removed by cesarean section in each group. Morphological development parameters were measured in each fetus and histopathological, biochemical and genetic analyses were conducted on the fetuses. The remaining pregnant rats in each group gave birth to the fetuses vaginally and biochemical, histopathological, genetic and cognitive function tests were conducted when the pups were 8 weeks old. AA administration caused adverse effects on fetus number, fetal weight, crown-rump length, placenta and brain weight. AA negatively affected malondialdehyde, reduced glutathione, total oxidant and antioxidant status, brain derived neurotrophic factor (BDNF) levels, brain tissue morphology, histopathology error score and gene expression (BDNF/β-actin mRNA ratio) in fetuses. AA administration caused disruption of biochemical, histopathological and cognitive functions in adult rats. Vitamin E provided protection against neurotoxicity in both fetuses and adult rats. We conclude that exposure to AA during pregnancy should be avoided and adequate amounts of antioxidants, such as vitamin E, should be consumed.

María Martinez-Ferran, Fabian Sanchis-Gomar, Carl J Lavie, Giuseppe Lippi, Helios Pareja-Galeano

Antioxidants (Basel) . 2020 Apr 29;9(5):E372. doi: 10.3390/antiox9050372.

Abstract

Free radicals produced during exercise play a role in modulating cell signaling pathways. High doses of antioxidants may hamper adaptations to exercise training. However, their benefits are unclear. This review aims to examine whether vitamin C (VitC) and/or vitamin E (VitE) supplementation (SUP) prevents exercise-induced muscle damage. The PubMed, Web of Science, Medline, CINAHL, and SPORTDiscus databases were searched, and 21 articles were included. Four studies examined the effects of acute VitC SUP given pre-exercise: in one study, lower CK levels post-exercise was observed; in three, no difference was recorded. In one study, acute VitE SUP reduced CK activity 1 h post-exercise in conditions of hypoxia. In three studies, chronic VitE SUP did not reduce CK activity after an exercise session. Chronic VitE SUP did not reduce creatine kinase (CK) concentrations after three strength training sessions, but it was effective after 6 days of endurance training in another study. Chronic SUP with VitC + E reduced CK activity post-exercise in two studies, but there was no such effect in four studies. Finally, three studies described the effects of chronic VitC + E SUP and long-term exercise, reporting dissimilar results. To conclude, although there is some evidence of a protective effect of VitC and/or VitE against exercise-induced muscle damage, the available data are not conclusive.

Jun Yang, Xuemei Ding, Shiping Bai, Jianping Wang, Qiufeng Zeng, Huanwei Peng, Zhuowei Su, Yue Xuan, Gregory Scott Fraley, Keying Zhang

J Anim Physiol Anim Nutr (Berl) . 2020 Apr 28. doi: 10.1111/jpn.13371.

Abstract

This research aims to evaluate the effects of maternal vitamin E (VE) dietary supplementation on the egg characteristics, hatchability and antioxidant status of the embryo and newly hatched chicks of prolonged storage eggs. A total of 576 75-week-old Ross 308 breeder hens were randomly allocated into three dietary VE treatments (100, 200 and 400 mg/kg) with 6 replicates of 32 hens, for a 12-week feeding trial. At week 12, a total of 710 eggs were collected over a 5-day period, and eggs per treatment were attributed into 5 replicates and stored for 14 days until incubation. The egg yolk, trunk and head of 7-day-old embryo and the serum, liver, brain and yolk sac of newly hatched chicks were sampled for the evaluation of antioxidant status. Results showed that as maternal dietary VE levels increased, yolk α-tocopherol concentration increased (p < .05). Compared with 100 mg/kg VE, the use of 200 and 400 mg/kg VE increased the hatchability of set/fertile eggs and total antioxidant capacity (T-AOC) of liver and serum in chicks (p < .05), and decreased both the early embryonic mortality and the malondialdehyde (MDA) content of trunk and head in 7-day-old embryos (p < .05); moreover, 400 mg/kg VE increased the yolk T-AOC (p < .05) and decreased yolk and brain MDA content of chicks (p < .05). Brain T-AOC of chicks in 200 mg/kg VE group was improved compared to that of chicks in 100 mg/kg VE group (p < .05). In conclusion, maternal dietary VE at 200 or 400 mg/kg could increase hatchability by decreasing early embryonic mortality and increasing the antioxidant status of egg yolk, embryo and newly hatched chicks as breeder egg storage was prolonged to 14-18 days. The suitable VE level for the broiler breeder diet was 200 mg/kg as breeder egg storage was prolonged.

Wu K, Zhu J, Zhou L, Shen L, Mao Y, Zhao Y, Gao R, Lou Z, Cai M, Wang B

Br J Nutr. 2020 Apr 28;123(8):841-848. doi: 10.1017/S0007114520000239. Epub 2020 Jan 22.

Abstract

Human milk fat is specially tailored to supply the developing infant with adequate and balanced nutrients. The present study aimed to quantify the composition of fatty acids, tocopherols and carotenoids in human milk, with special emphasis on the lactational changes. Colostrum, transitional and mature milk samples were collected longitudinally from the same forty-two healthy, well-nourished Chinese mothers. Fatty acids were quantified by GC with carotenoids (carotenes and xanthophylls) and tocopherols (α-, γ-tocopherol) determined by HPLC. Total fatty acid (TFA) content increased from 15·09 g/l in colostrum to 32·57 g/l in mature milk with the percentages of DHA and arachidonic acid (ARA) decreased. The ratio of n-6:n-3 PUFA and ARA:DHA remained constant during lactation at about 11:1 and 1·3:1, respectively. Both α-tocopherol and γ-tocopherol decreased over lactation with the ratio of α-:γ-tocopherol declined significantly from 7·21:1 to 4·21:1 (P < 0·001). Carotenoids all dropped from colostrum to mature milk as the less polar carotenes dropped by 88·67 %, while xanthophylls only dropped by 35·92 %. Lutein was predominated in both transitional and mature milk carotenoids (51·64-52·49 %), while colostrum carotenoids were mainly composed of lycopene (32·83 %) and β-carotene (30·78 %). The concentrations of tocopherols and xanthophylls but not carotenes were positively associated with TFA content in milk. These results suggested that colostrum and mature milk contained divergent lipid profiles and selective transfer mechanisms related to polarity might be involved. The present outcomes provide new insights for future breast-feeding studies, which also add in scientific evidences for the design of both initial and follow-on infant formulas.

Rinkoo Dalan, Liuh Ling Goh, Chien Joo Lim, Aruni Seneviratna, Huiling Liew, Cherng Jye Seow, Lian Xia, Daniel E K Chew, Melvin K S Leow, Bernhard O Boehm

Nutr Diabetes . 2020 Apr 27;10(1):13. doi: 10.1038/s41387-020-0116-7.

Abstract

Aims: Vitamin E (Vit-E) may preferentially improve cardiovascular risk in haptoglobin 2-2 (Hp2-2) genotype diabetes individuals. We studied the impact of Vit-E supplementation on vascular function in diabetes individuals stratified by haptoglobin genotype in Singapore.

Methods: In this 24-week, double blind, placebo-controlled RCT, we recruited 187 subjects (101 Hp2-2, 86 non-Hp2-2).

Intervention: alpha-tocopherol-400 IU.

Primary outcome: Change in EndoPAT-derived reactive-hyperaemia index (RHI) and augmentation index (AIx); Secondary Outcomes: Pulse-Wave velocity (Sphygmocor-PWV), carotid intima media thickness (CIMT), inflammation (hsCRP), derivatives of reactive-oxygen metabolites (dROMs), biological antioxidant-potential (BAPs), HbA1c, LDL-C, HDL-C and oxidised LDL-C (ox-LDL).

Results: Overall, with Vit-E supplementation no significant change in RHI, PWV, CIMT, hsCRP, dROMS, BAPs, HDL-C and HbA1c was observed (p > 0.05); an increase in LDL-C with concomitant decrease in ox-LDL, and incidentally increase in eGFR was observed (p < 0.05). No interaction effect with haptoglobin genotype was seen for all outcomes (p > 0.05). Subgroup analysis: In the non-Hp-2-2 group, Vit-E supplementation led to a higher EndoPAT-derived AIx, accompanied by higher LDL and ox-LDL concentrations (p < 0.05); Hp2-2 group: Vit-E supplementation led to higher eGFR when compared to the non-Hp2-2 group (exploratory) (p < 0.05). We observed an interaction effect for baseline haptoglobin concentration (threshold > 119 mg/dl) with intervention in terms of increased EndoPAT-derived AIx in the Hp > 119 mg/dl group whereas no change in the group with Hp ≤ 119 mg/dl.

Conclusion: Vit-E supplementation did not show any preferential benefit or deleterious effect on vascular function in Hp2-2 diabetes subjects in Singapore. A possible deleterious effect of an increase in arterial stiffness in individuals with Hp > 119 mg/dl was observed. Future studies should consider personalisation based on baseline Hp concentrations in patients with T2DM rather than just Hp2-2 genotype to evaluate impact on the detailed lipid pathways, cardiac and renal physiology. The impact of ethnic differences needs to be explored in greater details.

Jaime Ruiz-Tovar, Alejandro Garcia, Carlos Ferrigni, Manuel Duran

Obes Surg . 2020 Apr 27. doi: 10.1007/s11695-020-04635-9.

Abstract

Purpose: Postoperative pain after laparoscopic surgery has 3 components: parietal, visceral, and associated with pneumoperitoneum. Visceral pain accounts for around 30% of the total pain and is less amenable to be controlled by multimodal analgesia. The topical application of vitamin E ointment has demonstrated an anti-inflammatory effect in the local inflammatory response against surgical aggression. Vitamin E has been also associated with a reduction in postoperative pain of skin wounds. The aim of this study was to evaluate the effect of the topical application of vitamin E acetate on staple lines and anastomoses of Roux-en-Y gastric bypass, as part of a multimodal analgesia scheme within an Enhanced Recovery After Surgery (ERAS) program.

Methods: A prospective randomized clinical trial was performed. Patients were divided into 2 groups: patients receiving a topical application of vitamin E on staple lines and anastomoses (G1) and patients not receiving it (G2). The primary endpoint was postoperative pain, as measured by VAS 24 h after surgery. Secondary outcomes include morphine rescue needs, acute phase reactants 24 h after surgery, and hospital stay.

Results: One hundred forty patients were included, 70 in each group. Postoperative pain was 10 mm in G1 and 21.8 mm in G2 (p < 0.001). Morphine needs within the first 24 h were 2.9% in G1 and 13.2% in G2 (p = 0.026). C-reactive protein levels were significantly lower in G1 (8.7 mg/dL vs 11.9; p = 0.016). Mean hospital stay was 2.1 days in G1 and 2.9 in G2 (p = 0.019).

Conclusion: Topical application of vitamin E reduces postoperative pain and acute phase reactants, allowing an earlier discharge.