Hepatic and renal tissue damage in Balb/c mice exposed to diisodecyl phthalate: The role of oxidative stress pathways

Chen Y, Li C, Song P, Yan B, Yang X, Wu Y, Ma P

Food Chem Toxicol. 2019 Jun 20;132:110600. doi: 10.1016/j.fct.2019.110600. [Epub ahead of print]

Abstract

Diisononyl phthalate (DIDP) is commonly used as a plasticizer in industrial and consumer products, however, its toxicity remains unclear. This study investigated the possible involvement of oxidative stress in DIDP-induced liver and kidney toxicity. Liver function and kidney function, tissue lesions, oxidative stress biomarkers, inflammatory mediators and apoptosis factors were investigated in this study. The results showed that oral exposure to DIDP induced a marked increase in lever of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urinary nitrogen (UREA) and creatinine (CREA), decrease in albumin (ALB) level, as well as causing hepatic and renal histopathological change. Investigation of the role of oxidative stress pathways showed that DBP exposure could lead to a significant increase in levels of reactive oxygen species (ROS), malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB), while a decrease in glutathione (GSH) levels were observed. Administration of vitamin E to DIDP-treated mice restored these biochemical parameters to within normal levels, and resulted in less damage to livers and kidneys. Overall, these results suggest that the oxidative stress pathway is involved in DIDP-induced toxicity.

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Vitamin E Promotes Bone Formation in a Distraction Osteogenesis Model

Akçay H, Kuru K, Tatar B, Şimşek F

J Craniofac Surg. 2019 Jun 20. doi: 10.1097/SCS.0000000000005685. [Epub ahead of print]

Abstract

The long consolidation period of distraction osteogenesis (DO) may lead to complications such as pain, infection, fracture, scar formation, malunion and delayed union. The aim of this study was to evaluate the effect of systemic Vitamin E application during mandibular DO on new bone regeneration in a rabbit model. 16 adult male 8 months old New Zealand rabbits underwent mandibular lengthening with a distractor for the study. After the latency period of 5 days, the distractor was activated at a rate of 0.5 mm/12 hours for 7 days. Experimental animals received 200 mg/kg injections of α-tocopherol intraperitoneally for 7 days starting with the operation. After the consolidation period of 30 days, rabbits were sacrificed. Lengthened mandibles were obtained and subjected to dual-energy X-ray absorptiometry (DXA), radiologic and histomorphometric analysis. Statistically, bone mineral density and bone mineral content values were found to be significantly higher in the experimental group than the control group during DXA analysis. Rabbits in the experimental group had statistically higher scores in terms of osteoblast, osteoclast, vessel numbers and newly formed bone area than the control group. Results of the present study showed that systemic Vitamin E application during DO may stimulate new bone formation in rabbits and thus results in shortened treatment time.

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Associations between fat-soluble vitamins and lipid profile in overweight population

Piran S, Sarmasti S, Shabani M, Kakavandi N, Hosseni B, Khosravi M, Resaee S, Soltanmohammadi E, Naseri F, Ghasempour G, Mohammadi A, Najafi M

Recent Pat Food Nutr Agric. 2019 Jun 18. doi: 10.2174/2212798410666190618152134. [Epub ahead of print]

Abstract

METHODS:

A total of 120 overweight subjects participated in this study. The circulating PCSK9 and vitamin D were measured by ELISA technique. The serum vitamin A and vitamin E amounts were simultaneously measured by HPLC method. The serum small dense LDL-Cholesterol (sdLDL-C) values were evaluated using heparin-Mg2+ precipitation technique. The lipid profile was measured by routine laboratory techniques.

RESULTS:

The serum vitamin E values correlated significantly to vitamin A (r=0.47, P= 0.0001), VLDL-C (r= 0.30, P= 0.002), total cholesterol (r=0.309, P= 0.001), PCSK9 (r=0.233, P=0.01) and total triglyceride (r= 0.61, P= 0.0001) values. The circulating PCSK9 values correlated significantly to LDL-C (r=0.17, P=0.05) and total cholesterol (r=0.23, P=0.009) values. However, there were not correlations between the levels of serum D and A vitamins, the serum LDL-C, sdLDL-C and total cholesterol values.

CONCLUSION:

The data showed the correlations between serum vitamin E and PCSK9-related LDL-C values lower than the normal range. Furthermore, the results suggested a nutritional need on the patents considering supplementation or fortification of vitamin E for the overweight subjects with higher LDL-C levels.

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Effect of vitamin E on severity and duration of cyclic mastalgia: A systematic review and meta-analysis

Hajizadeh K, Alizadeh Charandabi SM, Hasanzade R, Mirghafourvand M

Complement Ther Med. 2019 Jun;44:1-8. doi: 10.1016/j.ctim.2019.03.014. Epub 2019 Mar 22.

Abstract

OBJECTIVES:

A systematic review was conducted to assess the effect of vitamin E on the severity and duration of Cyclic Mastalgia compared to vitamin B6, fish oil, herbal medicines and placebo.

DESIGN:

A systematic review and meta-analysis of clinical trials.

METHODS:

A search was carried out in PubMed, Cochrane Library, Embase, Scopus and Google Scholar and Persian databases for articles published from 1980 to 2018. The data obtained were analyzed in RevMan and reported in forest plots. The Odds Ratio (OR) was used to find the effect for the dichotomous data and the Standardized Mean Difference (SMD) for the continuous data. The heterogeneity of the studies was assessed using I2 and the Random Effects Model was used instead of the Fixed Effects Model if I2>25%.

RESULTS:

A total of 1051 titles and abstracts were extracted. Fourteen articles ultimately remained, and 11 of them were entered into the meta-analysis. The meta-analysis showed significant differences between vitamin E and placebo in the severity (SMD=-0.51; 95% CI=-0.21 to -0.82) and duration (MD=-1.47; 95% CI=-0.91 to -2.57) of cyclic mastalgia, although herbal medicines had a greater effect on the severity of mastalgia than vitamin E (SMD = 0.51, 95% CI = 0.06 to 0.96).

CONCLUSION:

Although herbal medicines are more effective than vitamin Evitamin E reduces both the severity and duration of the disorder compared to placebos, which only reduce its severity, and can therefore be considered a treatment with minimum side-effects. Due to the high heterogeneity of the studies, the researchers recommend further research on the subject using a standard tool based on the CONSORT statement.

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Effects of N-nitro L-arginine methyl ester and α-tocopherol on testicular oxidative stress caused by exposure to cigarette smoke.

Kara Y, Akyuz F

Andrologia. 2019 Jun 17:e13355. doi: 10.1111/and.13355. [Epub ahead of print]

Abstract

Testis is a rich organ with blood vessels. For this reason, it is possible that the toxic substances of the cigarette carried in the blood change the balance between the oxidant and the antioxidant system in this organ. In this study, it was aimed to investigate the effects of N-nitro L-arginine methyl ester and α-tocopherol on testicular oxidative stress caused by exposure to cigarette smoke. 45 wistar male rats were used in the study. Five groups were formed: control, cigarette smoke, cigarette smoke + α-tocopherol, cigarette smoke + N-nitro L-arginine methyl ester and cigarette smoke + α-tocopherol + N-nitro L-arginine methyl ester. Biochemical and histological evaluations were performed to determine the damage caused by cigarette smoke. It was observed that there were structural and functional disturbances at the cellular and hormonal level in the smoking group. Biochemical evaluations showed that cellular damage was reduced in treatment groups. Histological examinations were revealed that the damage caused by cigarette smoke exposure was eliminated in treatment groups. As a result of our study, we think that oxidative damage and hormonal irregularity in the testes tissue caused by cigarette smoke exposure can be improved with α-tocopherol and N-nitro L-arginine methyl ester application.

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α-Tocopherol Restriction Dysregulates Neurogenesis-Related Gene Expression in Brains of Weanling α-Tocopherol Transfer Protein Knockout Mice (P11-134-19)

Ranard K, Kuchan M, Erdman J Jr

Curr Dev Nutr. 2019 Jun 13;3(Suppl 1). pii: nzz048.P11-134-19. doi: 10.1093/cdn/nzz048.P11-134-19. eCollection 2019 Jun.

Abstract

OBJECTIVES:

Humans with vitamin E (α-tocopherol, αT) deficiency develop neurological disorders. Similarly, α-tocopherol transfer protein knockout (Ttpa-/- ) mice have low vitamin E status and exhibit neurodegeneration with age. Shifts in the transcriptome may precede behavioral manifestations of vitamin E deficiency, but it is unknown how early abnormalities occur. Aberrations during brain development could have lifelong implications. The study objective was to determine how αT restriction during early-life affects the expression of pre-selected neurogenesis-related genes in the cerebellum (CB) and cerebral cortex (CC) of Ttpa-/- weanlings.

METHODS:

Female Ttpa+/+ (n = 9) and Ttpa-/- (n = 10) mice were nursed by Ttpa+/- dams until postnatal day 21. Dams were fed AIN-93G diet (75 mg αT/kg diet) during days 1-9 of gestation, and αT-stripped diet for the rest of the study. Homogenized brain tissues from 21 day old weanlings were used to measure αT concentrations via HPLC-PDA. The expression of genes critical for brain development (RoraShh), myelination (Plp1, Cntnap1, Mbp, Mobp, Nr1h3), synaptic function (Cplx1, Cplx2, Vamp2, Necab1, Prkcg), and αT cellular uptake (Scarb1) were measured in the CB and CC via real-time qPCR.

RESULTS:

αT levels were significantly decreased in brains of Ttpa-/- mice (0.1 ± 0.1 nmol/g) compared to Ttpa+/+ mice (9.8 ± 1.4 nmol/g) (P < 0.001), confirming their low αT status. RoraShhCntnap1, and Mbp were significantly upregulated (P < 0.05) in both the CB and CC of Ttpa-/- mice, while several genes were only upregulated in one brain region (Plp1 in the CB, Mobp in the CC). Necab1 and Scarb1 were significantly downregulated in the CB of Ttpa-/- mice (P < 0.05).

CONCLUSIONS:

αT restriction during the fetal and postnatal periods alters the expression of neurogenesis-related genes. These findings support a role for αT in brain development.

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Vitamin E Prevents ΔN-Bcl-xL-associate Mitochondrial Dysfunction in Primary Hippocampal Neurons (P14-024-19)

Park HA, Mnatsakanyan N, Broman K, Jonas E

Curr Dev Nutr. 2019 Jun 13;3(Suppl 1). pii: nzz052.P14-024-19. doi: 10.1093/cdn/nzz052.P14-024-19. eCollection 2019 Jun.

Abstract

OBJECTIVES:

B-cell lymphoma-extra large (Bcl-xL) is a pro-survival protein localized to mitochondria. Bcl-xL is reported to support brain function by enhancing neuronal energy metabolism, synapse formation, and neurite outgrowth. However, under exposure to excitotoxic stimulation and subsequent oxidative stress, Bcl-xL undergoes caspase dependent cleavage to ∆N-Bcl-xL. Accumulation of ∆N-Bcl-xL is associated with neuronal death; thus, approaches that prevent ∆N-Bcl-xL accumulation protect neurons from excitotoxic insult. In this study, we hypothesize that ∆N-Bcl-xL formation is regulated by redox status in mitochondria. We thus tested if production of ∆N-Bcl-xL can be inhibited by the fat-soluble antioxidant α-tocotrienol (TCT) given its ability to scavenge free radicals produced in the mitochondrial membrane.

METHODS:

Primary hippocampal neurons were treated with α-TCT, glutamate, or a combination of both, and mitochondrial oxidative stress, mitochondrial potential, caspase activity, and ∆N-Bcl-xL protein levels were quantified.

RESULTS:

Glutamate caused abnormalities in mitochondrial function leading to neuronal death. The antioxidant α-TCT protected neurons from glutamate-induced mitochondrial dysfunction and cytotoxicity. α-TCT treatment protected against cleavage of full length anti-apoptotic Bcl-xL to form pro-death ∆N-Bcl-xL. α-TCT significantly attenuated glutamate-induced reactive oxygen species (ROS) formation, caspase 3 activation and ∆N-Bcl-xL formation at mitochondria.

CONCLUSIONS:

Our data suggests that oxidative stress production during excitotoxicity is responsible for the formation of ∆N-Bcl-xL. Thus, application of a lipophilic antioxidant such as vitamin E is neuroprotective by improving mitochondrial redox status and preventing production of neurotoxic ∆N-Bcl-xL.

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Improvement of Sperm Motility Within One Month Under Selenium and Vitamin E Supplementation in Four Infertile Dogs with Low Selenium Status

Domosławska A, Zduńczyk S, Janowski T

J Vet Res. 2019 Jun 12;63(2):293-297. doi: 10.2478/jvetres-2019-0025. eCollection 2019 Jun.

Abstract

INTRODUCTION:

Significant improvement of sperm motility within one month effected by oral supplementation of selenium and vitamin E was described in four infertile male dogs which failed to conceive in their last three matings with different bitches.

MATERIAL AND METHODS:

The dogs (a Golden Retriever, an English Cocker Spaniel, and two Tibetan Mastiffs) were supplemented daily with selenium (Se) (0.6 mg/kg organic Se yeast) and vitamin E (vit. E) (5 mg/kg) per os for 60 days. Semen was collected on days 0, 30, 60, and 90. The sperm concentration and motility parameters were evaluated by the CASA system, sperm morphology was explored by Diff-Quick staining, and live and dead spermatozoa were differentiated by eosin/nigrosin staining. The concentrations of Se and vit. E were measured in peripheral blood serum on semen collection days.

RESULTS:

Before administration, the concentrations of Se in blood plasma were low (86.0-165.0 μg/L). After 30 days of treatment there was an observable improvement in total and progressive sperm motility and kinematic parameters (VAP, VSK, VCL, ALH, BCF, and RAPID). The percentages of live and normal morphology sperm cells were also higher. There was also an observable increase in Se and vitamin Econcentrations in blood serum. Bitches were successfully mated and delivered four to six puppies.

CONCLUSION:

Supplementation with Se and vit. E improved rapid sperm motility and restored fertility in infertile dogs with low Se status.

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Evidence for antinociceptive effects of combined administration of vitamin E and celecoxib in tail-flick and formalin test in male rats

Shamsi Meymandi M, Sepehri G, Izadi G, Zamiri Z

Pharmacol Rep. 2019 Jun;71(3):457-464. doi: 10.1016/j.pharep.2019.02.005. Epub 2019 Feb 12.

Abstract

BACKGROUND:

The aim of this study was to evaluate the effect of vitamin E co-administration with celecoxib in thermal and inflammatory pain in two model of pain assessment including thermal tail flick test of acute pain and formalin induced inflammatory model in adult male rats.

METHODS:

Seventy two male Wistar rats were divided into a vehicle received intraperitoneally olive oil, indomethacin (20 mg/kg), vitamin E(100, 200 and 400 mg/kg), celecoxib (3, 10, 30 and 60 mg/kg) groups, and combination groups received the combination of vitamin E (100 and 200 mg/kg) and celecoxib (3, 10 and 30 mg/kg). All drugs were dissolved in olive oil. Antinociceptive effect in tail-flick was measured using Area Under Curve (AUC) of responses and Maximum Possible Effect (%MPE) and pain score was used for antinociceptive response in formalin test.

RESULTS:

Vitamin E and celecoxib changed time course of pain scores in a dose related manner in formalin test but not in tail-flick test. Vitamin E (200 mg/kg) had no effect and merely 60 mg/kg of celecoxib increased %MPE and AUC in tail-flick. The combination of vitamin E(100 or 200 mg/kg) with celecoxib (3 or 10 mg/kg) decreased pain scores compared to vehicle in both phases of formalin test, while in chronic phase (II) the pain scores of combination groups were also decreased compared to vitamin E and celecoxib. However, in tail-flick test the combination of ineffective doses of vitamin E (200 mg/kg) and celecoxib (10 and 30 mg/kg) increased %MPE and AUC compared to vehicle but not compared to celecoxib or vitamin E.

CONCLUSIONS:

Vitamin E and celecoxib showed a dose related antinociceptive effect in inflammatory but not in thermal model of acute pain. However the co-administration of vitamin E with celecoxib caused a significant increase in the antinociceptive effect which was similar to indomethacin, as a standard anti-inflammatory drug. So we suggest the concomitant use of vitamin E with celecoxib and other NSAIDs for potentiation of both anti- inflammatory and analgesic response, as well as the reduction of cardiovascular side effects of celecoxib.

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