Vitamin E (α‑tocopherol) ameliorates aristolochic acid‑induced renal tubular epithelial cell death by attenuating oxidative stress and caspase‑3 activation.

Wu TK, Pan YR, Wang HF, Wei CW, Yu YL

Mol Med Rep. 2018 Jan;17(1):31-36. doi: 10.3892/mmr.2017.7921. Epub 2017 Oct 27.

Abstract

Aristolochic acid (AA) is a component identified in traditional Chinese remedies for the treatment of arthritic pain, coughs and gastrointestinal symptoms. However, previous studies have indicated that AA can induce oxidative stress in renal cells leading to nephropathy. α‑tocopherol exists in numerous types of food, such as nuts, and belongs to the vitamin E isoform family. It possesses antioxidant activities and has been used previously for clinical applications. Therefore, the aim of the present study was to determine whether α‑tocopherol could reduce AA‑induced oxidative stress and renal cell cytotoxicity, determined by cell survival rate, reactive oxygen species detection and apoptotic features. The results indicated that AA markedly induced H2O2 levels and caspase‑3 activity in renal tubular epithelial cells. Notably, the presence of α‑tocopherol inhibited AA‑induced H2O2 and caspase‑3 activity. The present study demonstrated that antioxidant mechanisms of α‑tocopherol may be involved in the increased survival rates from AA‑induced cell injury.

Beytut E, Yilmaz S, Aksakal M, Polat S

J Trace Elem Med Biol. 2018 Jan;45:131-135. doi: 10.1016/j.jtemb.2017.10.005. Epub 2017 Oct 16.

Abstract

Acute exposure to high doses of glucocorticoids (GCs) may potentially increase the basal levels of reactive oxygen species (ROS) by altering the defence capacity against oxidative damage. Also, antioxidants may affect the oxidative breakdown of tissues. Therefore, the aim of this work was to determine the effects of dietary intake vitamin E and selenium (Se) on lipid peroxidation (LPO) as thiobarbituric acid reactive substances (TBARS) and on the antioxidative defence mechanisms in the brain of rats treated with high doses of prednisolone. Two hundred and fifty adult male Wistar rats were randomly divided into five groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily supplement in their drinking water of 20mg vitamin E, 0.3mg Se, and a combination of vitamin E and Se, respectively, for 30days. For 3days subsequently, the control (group 1) was treated with a placebo, and the remaining 4 groups were injected intramuscularly with 100mg/kg body weight (bw) prednisolone. After the last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48h and the activities of enzymes selenium-glutathione peroxidase (Se-GSH-Px) and catalase (CAT), and the levels of reduced glutathione (reduced GSH) and TBARS in their brains were measured. Se-GSH-Px and CAT enzyme activities, and reduced GSH levels in the prednisolone treatment group (group 2) began to decrease gradually at 4h (p<0.01, p<0.05, respectively), falling respectively to 60, 50, and 40% of the control levels by 24h (p<0.001, p<0.01), and recovering to the control levels at 48h. In contrast, prednisolone administration caused an increase in the brain TBARS, reaching up to six times the level of the control at 24h (p<0.001). However, supplementation with vitamin E and Se had a preventive effect on the elevation of the brain TBARS and improved the diminished activities of antioxidative enzymes and the levels of reduced GSH. Therefore, the present study attempts to determine the sequence of cellular membrane damage in the brain of the rats after high doses GC administration and the possible roles in vivo of vitamin E and Se, and their combination.

Baghcheghi Y, Beheshti F, Shafei MN, Salmani H, Sadeghnia HR, Soukhtanloo M, Anaeigoudari A, Hosseini M

Metab Brain Dis. 2017 Dec 30. doi: 10.1007/s11011-017-0176-0. [Epub ahead of print]

Abstract

The effects of vitamin E (Vit E) on brain derived neurotrophic factor (BDNF) and brain tissues oxidative damage as well as on learning and memory impairments in juvenile hypothyroid rats were examined. The rats were grouped as: (1) Control; (2) Propylthiouracil (PTU); (3) PTU-Vit E and (4) Vit E. PTU was added to their drinking water (0.05%) during 6 weeks. Vit E (20 mg/kg) was daily injected (IP). Morris water maze (MWM) and passive avoidance (PA) were carried out. The animals were deeply anesthetized and the brain tissues were removed for biochemical measurements. PTU increased the escape latency and traveled path in MWM (P < 0.001). It also shortened the latency to enter the dark compartment of PA as well as the time spent in the target quadrant in probe trial of MWM (P < 0.01-P < 0.001). All the effects of PTU were reversed by Vit E (P < 0.01-P < 0.001). PTU administration attenuated thiol and BDNF content as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in the brain tissues while increased molondialdehyde (MDA). Moreover, Vit E improved BDNF, thiol, SOD and CAT while diminished MDA. The results of the present study showed that Vit E improved BDNF and prevented from brain tissues oxidative damage as well as learning and memory impairments in juvenile hypothyroid rats.

Bao A, Yang H, Ji J, Chen Y, Bao W, Li F, Zhang M, Zhou X, Li Q, Ben S

Respir Res. 2017 Dec 29;18(1):216. doi: 10.1186/s12931-017-0697-4.

Abstract

BACKGROUND:

Exposure to ambient ozone (O₃) increases the susceptivity to allergens and triggers exacerbations in patients with asthma. However, the detailed mechanisms of action for O₃ to trigger asthma exacerbations are still unclear.

METHODS:

An ovalbumin (OVA)-established asthmatic mouse model was selected to expose to filtered air (OVA-model) or 1.0 ppm O₃(OVA-O₃ model) during the process of OVA challenge. Next, the possible involvements of p38 MAPK and oxidative stress in the ozone actions on the asthma exacerbations were investigated on the mice of OVA-O₃ model by treating them with SB239063 (a p38 MAPK inhibitor), and/or the α-tocopherol (antioxidant). Biological measurements were conducted including airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL), inflammation in the airway lumen and lung parenchyma, the phosphorylation of p38 MAPK and heat shock protein (HSP) 27 in the tracheal tissues, and the malondialdehyde (MDA) content and the glutathione peroxidase (GSH-Px) activity in lung tissues.

RESULTS:

In OVA-allergic mice, O3 exposure deteriorated airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL) and pulmonary inflammation, accompanied by the increased oxidative stress in lung tissues and promoted p38 MAPK and HSP27 phosphorylation in tracheal tissues. Administration of SB239063 (a p38 MAPK inhibitor) on OVA-O3 model exclusively mitigated the Raw, the CL, and the BAL IL-13 content, while α-tocopherol (antioxidant) differentially reduced the BAL number of eosinophils and macrophages, the content of BAL hyaluronan, the peribronchial inflammation, as well as the mRNA expression of TNF-α and IL-5 in the lung tissues of OVA-O3 model. Administration of these two chemical inhibitors similarly inhibited the AHR, the BAL IFN-γ and IL-6 production, the perivascular lung inflammation and the lung IL-17 mRNA expression of OVA-O3 model. Interestingly, the combined treatment of both compounds together synergistically inhibited neutrophil counts in the BALF and CXCL-1 gene expression in the lung.

CONCLUSIONS:

O₃ exposure during the OVA challenge process promoted exacerbation in asthma. Both p38 MAPK and oxidative stress were found to play a critical role in this process and simultaneous inhibition of these two pathways significantly reduced the O₃-elicited detrimental effects on the asthma exacerbation.

Rios R, Raya AI, Pineda C, Rodriguez M, Lopez I, Aguilera-Tejero E

BMC Nephrol. 2017 Dec 28;18(1):374. doi: 10.1186/s12882-017-0790-4.

Abstract

BACKGROUND:

High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal disease. Previous studies have revealed that high fat diets promote vascular calcification in uremic rats. Moreover, vitamin E has been shown to prevent uremic calcifications in genetically obese Zucker rats fed standard diet. The objective of this study was to investigate the influence of vitamin E supplementation on the development of extraskeletal calcifications in non-obese (wild type) uremic rats fed high fat diets.

METHODS:

Wistar rats (n = 32) were preconditioned by feeding either a normal (NF) or high fat (HF) diet for 45 days and subsequently were subjected to 5/6 nephrectomy (Nx). Just before performing the first Nx step, a blood sample (Pre-Nx) was obtained. After Nx rats were switched to a diet with 0.9% phosphorus and supplemented with calcitriol. Also, after Nx, half of the rats from each group (NF and HF) were treated with vitamin E (VitE) in the diet (30,000 mg/kg) and the other half were maintained on basic VitE requirements (27 mg/kg). Thus, rats were allotted to four experimental groups: Nx-NF (n = 8), Nx-NF-VitE (n = 8), Nx-HF (n = 8) and Nx-HF-VitE (n = 8). At the time of sacrifice (day 66), blood and tissue samples were obtained.

RESULTS:

Feeding a HF diet for 45 days did not increase body weight but elicited hyperglycemia, hypertriglyceridemia, an increase in plasma fibroblast growth factor 23 and a reduction in plasma calcitriol concentrations. After Nx, rats fed HF diet showed substantial extraskeletal calcification with aortic calcium content that was higher than in rats fed NF diet. Supplementation with VitE significantly (p < 0.05) reduced aortic (from 38.4 ± 8.8 to 16.5 ± 1.4 mg/g), gastric (from 5.6 ± 2.7 to 1.2 ± 0.4 mg/g) and pulmonary (from 1.8 ± 0.3 to 0.3 ± 0.2 mg/g) calcium content in rats on HF diets.

CONCLUSIONS:

Uremic rats fed HF diets developed more severe extraosseous calcifications than their normocaloric-fed counterparts and dietary VitE supplementation protected against uremic calcifications in rats fed HF diets. Thus, eating energy-rich foods should be discouraged in patients with renal disease and their deleterious effect may be ameliorated with adequate antioxidant supply.

Tian Y, Xiao Y, Wang B, Sun C, Tang K, Sun F

Biosci Rep. 2017 Dec 22. pii: BSR20171003. doi: 10.1042/BSR20171003. [Epub ahead of print]

Abstract

Although fluoride has been widely used in toothpaste, mouthwash, and drinking water to prevent dental caries, the excessive intake of fluoride can cause fluorosis which is associated with dental, skeletal, and soft tissue fluorosis. Recent evidences have drawn the attention to its adverse effects on male reproductive system that include spermatogenesis defect, sperm count loss, and sperm maturation impairment. Fluoride induces oxidative stress through the activation of mitogen activated protein kinase (MAPK) cascade which can lead to cell apoptosis. Vitamin E (VE) and lycopene are two common anti-oxidants, being protective to reactive oxygen species (ROS)-induced toxic effects. However, whether and how these two anti-oxidants prevent fluoride-induced spermatogenic cell apoptosis are largely unknown. In the present study, a male rat model for coal burning fluorosis was established and the histological lesions and spermatogenic cell apoptosis in rat testes were observed. The decreased expression of clusterin, a heterodimeric glycoprotein reported to regulate spermatogenic cell apoptosis, is detected in fluoride-treated rat testes. Interestingly, the co-administration with VE or lycopene reduced fluorosis-mediated testicular toxicity and rescued clusterin expression. Further, fluoride caused the enhanced Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) phosphorylation, which was reduced by VE or lycopene. Thus, VE and lycopene prevent coal burning fluorosis-induced spermatogenic cell apoptosis through the suppression of oxidative stress-mediated JNK and ERK signaling pathway, which could be an alternative therapeutic strategy for the treatment of fluorosis.

Sun B, Zhang X, Yin Y, Sun H, Ge H, Li W

J Trace Elem Med Biol. 2017 Dec;44:88-92. doi: 10.1016/j.jtemb.2017.06.004.

Abstract

OBJECT:

To investigate the effects of sulforaphane (SFN) and vitamin E (VE) on spatial learning and memory ability and oxidative damage of hippocampus in lead-exposed mice at lactation.

METHODS:

A total of 18 adult Kunming mice, all 12 female mice were divided into two groups by body weight randomly, 10 mice drank water containing 0.2% lead acetate at lactation, the other 2 mice drank lead free deionized water named as the normal group. Then, they were mated at a 1:2 ratio of male to female. After weaning, the pups were divided into 5 groups by weight randomly (10 each group): normal saline (NS) group, corn oil (CO) group, SFN group, VE group and SFN+VE group. They were subject to gavage daily for four weeks. Gavage doses of SFN and VE were 25mg/kg and 30 IU/kg respectively. Meanwhile, 10 pups of the normal group were selected randomly as the control (C) group. The C group was normally raised for 4 weeks. The spatial learning and memory ability of them were evaluated by the Morris water maze test, and the lead level in the blood was determined by polarography. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in hippocampus were measured by the kits.

RESULTS:

Compared with the NS and CO groups, the lead level in the blood of SFN and SFN+VE group had a significant decrease. In water maze test, the mice treated with SFN or/and VE performed better than mice of the NS and CO groups. In addition, a remarkable decrease in MDA level was found in mice treated with SFN or/and VE than those in NS and CO groups. What’s more, there was no statistical distinction of SOD activity in SFN group than that of NS group. SOD activity significantly increased was observed in VE and SFN+VE groups than that of CO group.

CONCLUSION:

Sulforaphane and vitamin E could ameliorate cognitive decline and oxidative damage in pups with lead exposure at lactation from maternal milk.

Rýdlová M, Růnová K, Száková J, Fučíková A, Hakenová A, Mlejnek P, Zídek V, Tremlová J, Mestek O, Kaňa A, Zídková J, Melčová M, Truhlářová K, Tlustoš P.

Biomed Res Int. 2017;2017:6759810. doi: 10.1155/2017/6759810. Epub 2017 May 30.

Abstract

The response of nutrient status and biochemical processes in (i) Wistar and (ii) spontaneously hypertensive (SHR) rats upon dietary intake of selenium- (Se-) enriched defatted rapeseed (DRS) and/or vitamin E fortification was examined to assess the health benefit of DRS in animal nutrition. Twenty-four individuals of each type of rat were used: The control group was fed with an untreated diet (Diet A). In Diets B and C, soybean meal was replaced with defatted DRS, which comprised 14% of the total diet. The selenized DRS application resulted in ~3-fold increase of Se content in the diet. Diet C was also fortified with the addition of vitamin E, increasing the natural content by 30%. The Se content of the blood and kidneys tended to increase in the DRS groups, where the changes were significant (P < 0.05) only in the case of SHR rats. The iodine (I) content and the proportion of iodide in rat livers indicated a lower transformation rate of iodide into organoiodine compounds compared to the control. Slight and ambiguous alterations in the antioxidative response of the rat were observed in the DRS groups, but the addition of vitamin E to the diet helped to moderate these effects.

Torshabi M, Rezaei Esfahrood Z, Jamshidi M, Mansuri Torshizi A, Sotoudeh S

Eur J Oral Sci. 2017 Dec;125(6):426-437. doi: 10.1111/eos.12375. Epub 2017 Oct 12.

Abstract

Nicotine has adverse cellular and molecular effects on oral mucosa, bone, and teeth. Vitamin E (α-tocopherol) and vitamin C (ascorbic acid) are biological antioxidants with positive effects on wound healing and bone formation. This in vitro study sought to assess the cytotoxic effects of different concentrations of nicotine and cotinine (a metabolite of nicotine) on MG-63 osteoblast-like cells and human gingival fibroblasts (HGFs) in the presence and absence of antioxidant vitamins E and C (separately and combined). Cell viability and proliferation were assessed using the methyl thiazol tetrazolium (MTT) assay. Cell migration was assessed using the scratch test, and expression of apoptosis-related genes was quantitatively analyzed using real-time PCR. Dose-dependent negative effects of nicotine on the morphology, viability, proliferation, and migration of MG-63 and HGF cells were statistically significantly greater than those of cotinine. Vitamin E (separately and combined with vitamin C) was statistically significantly more effective than vitamin C (at the concentration used in this study) at improving cell viability, proliferation, and migration, and at reducing apoptosis of cells exposed to nicotine or cotinine. Based on the positive results of this study, vitamin C and especially vitamin E (systemically and/or locally) may be useful in the repair and regeneration of oral hard and soft tissues in smokers.

Kanchi MM, Shanmugam MK, Rane G, Sethi G, Kumar AP

Drug Discov Today. 2017 Dec;22(12):1765-1781. doi: 10.1016/j.drudis.2017.08.001. Epub 2017 Aug 5.

Abstract

Vitamin E family members: tocotrienols and tocopherols are widely known for their health benefits. Decades of research on tocotrienols have shown they have diverse biological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective and skin protection benefits, as well as improved cognition, bone health, longevity and reduction of cholesterol levels in plasma. Tocotrienols also modulate several intracellular molecular targets and, most importantly, have been shown to improve lipid profiles, reduce total cholesterol and reduce the volume of white matter lesions in human clinical trials. This review provides a comprehensive update on the little-known therapeutic potentials of tocotrienols, which tocopherols lack in a variety of inflammation-driven diseases.