Has vitamin E any shreds of evidence in cisplatin-induced toxicity

Hakiminia B, Goudarzi A, Moghaddas A

J Biochem Mol Toxicol. 2019 May 21:e22349. doi: 10.1002/jbt.22349. [Epub ahead of print]

Abstract

Cisplatin is one of the highly consumed and effective antitumor agents whose clinical application is accompanied by nephrotoxicity adverse reaction. Also, other complications such as ototoxicity and hepatotoxicity are a matter of concern. Today, it is suggested that cisplatin-associated toxicities are mainly induced by free radicals production, which will result in oxidative organ injury. The evidence is growing over the protective effects of antioxidants on cisplatin-induced adverse reactions especially nephrotoxicity. The possible protective effects of vitamin E and its derivative in cisplatin-induced nephrotoxicity and ototoxicity are reviewed here at the light of pertinent results from basic and clinical research. Administration of vitamin E alone or in combination with other antioxidant agents could cause amelioration in oxidative stress biomarkers such as decreasing the level of malondialdehyde, reducing serum urea and creatinine, and also enhancing the activities of renal antioxidant enzymes including renal catalase, glutathione-S-transferase, and superoxide dismutase. Although the data from most of the studies are in favors of protective effects of vitamin E against cisplatin-induced toxicity, more clinical trials are needed to clarify the clinical importance of vitamin E administration as an antioxidant during cisplatin therapy in cancer condition.

Alghadir AH, Gabr SA, Iqbal ZA, Al-Eisa E

BMC Pediatr. 2019 May 17;19(1):156. doi: 10.1186/s12887-019-1528-1.

Abstract

BACKGROUND:

Although various studies have shown the effect of vigorous physical activity on academic achievements, no studies have investigated the effect of vitamin E levels on academic performance. The present study aimed to assess the association between physical activity, vitamin E levels and total antioxidant capacity on the academic performance and executive functions of adolescents aged 15-18 years.

METHODS:

The physical activity of participants was assessed according to the time spent engaging in moderate and intense exercise programs. Participants were classified into three groups representing mild, moderate, and high activity. Serum total antioxidant capacity was measured using a colorimetric assay kit. Vitamin E was estimated by the α- and γ-tocopherol levels in fasting serum samples using high-performance liquid chromatography paired with a diode array detector. School grades (ranging from 1.0, very poor; to 10.0, outstanding) were obtained at the end of the academic year to evaluate academic performance and executive functions.

RESULTS:

A total of 120 school students (mean age 16.36 ± 0.77 years; 70 boys, 50 girls) participated in the study. Academic performance was higher for students classified as moderately or highly active compared with those in the mild activity group. Serum levels of vitamin E, total antioxidant capacity, and leisure-time physical activity were also higher in the moderate and high activity groups. There was a significant correlation between age, gender, body mind index, α- and γ-tocopherol, total antioxidant capacity, leisure-time physical activity and academic performance.

CONCLUSIONS:

The academic performance and executive function scores were found to be positively correlated with age, gender, α- and γ-tocopherol, total antioxidant capacity, and physical activity; and were negatively correlated with body mind index. Our findings indicate that physical activity should be promoted during and after school hours, along with a healthy balanced diet including vitamin E.

Wong SY, Teo JSM, Chai SF, Yeap SL, Lau AJ

Toxicology. 2019 May 15;423:62-74. doi: 10.1016/j.tox.2019.05.005. [Epub ahead of print]

Abstract

Lithocholic acid is a cytotoxic bile acid oxidized at the C-3 position by human cytochrome P450 3A (CYP3A) to form 3-ketocholanoic acid, but it is not known whether this metabolite is cytotoxic. Tocotrienols, in their various isomeric forms, are vitamin E analogues. In the present study, the hypothesis to be tested is that tocotrienols inhibit CYP3A-catalyzed lithocholic acid 3-oxidation, thereby influencing lithocholic acid cytotoxicity. Our enzyme catalysis experiments indicated that human recombinant CYP3A5 in addition to CYP3A4, liver microsomes, and intestinal microsomes catalyzed lithocholic acid 3-oxidation to form 3-ketocholanoic acid. Liver microsomes with the CYP3A5*1/*3 and CYP3A5*3/*3 genotypes were associated with decreased lithocholic acid 3-oxidation. α-Tocotrienol, γ-tocotrienol, δ-tocotrienol, and a tocotrienol-rich vitamin E mixture, but not α-tocopherol (a vitamin E analogue), differentially inhibited lithocholic acid 3-oxidation catalyzed by liver and intestinal microsomes and recombinant CYP3A4 and CYP3A5. Compared to lithocholic acid 3-oxidation, CYP3A-catalyzed testosterone 6β-hydroxylation was inhibited to a lesser extent by α-tocotrienol, γ-tocotrienol, δ-tocotrienol, and a tocotrienol-rich vitamin Emixture. δ-Tocotrienol inhibited lithocholic acid 3-oxidation by a mixed mode. Like lithocholic acid, 3-ketocholanoic acid was also cytotoxic in human intestinal and liver cell models. δ-Tocotrienol decreased the extent of lithocholic acid 3-oxidation and this inhibition was associated with enhanced cytotoxicity in LS180 cells treated with δ-tocotrienol and lithocholic acid. Overall, vitamin E analogues inhibited in vitro lithocholic acid 3-oxidation in an isomer-dependent manner, with inhibition occurring with tocotrienols, but not α-tocopherol. The enhanced lithocholic acid toxicity by δ-tocotrienol in a human intestinal cell model warrants future investigations in vivo.

Liu X, Zhang Y, Yang X

Ecotoxicol Environ Saf. 2019 May 15;172:33-39. doi: 10.1016/j.ecoenv.2019.01.048. Epub 2019 Jan 19.

Abstract

Exposure to specific air pollutants has been demonstrated to induce damage in the brain. However, these studies ignore the effects of a combination of contaminants, and there is a high likelihood that people will be exposed to a mixture of contaminants in daily life. Our previous study showed that co-exposure to formaldehyde (FA) and PM2.5 induced damage in the mouse brain at the safe exposure level for FA or PM2.5 exposure alone, and that oxidative stress and inflammation may be involved in the toxicity mechanisms. A universal strategy to protect people exposed to FA and PM2.5 is urgently needed. To explore whether an exogenous substance could counteract the negative effects of exposure to these pollutants, we administered vitamin E (Vit E) to the experimental animals. The results showed that administration of Vit E in tandem with the FA and PM2.5 co-exposure, reduced the extent of damage to the mouse brain. Down-regulation of oxidative stress and inflammation were proposed to explain the protective effects of Vit E. This research provides a universal strategy to effectively protect people who are exposed to FA and PM2.5 simultaneously.

Sepidarkish M, Akbari-Fakhrabadi M, Daneshzad E, Yavari M, Rezaeinejad M, Morvaridzadeh M, Heshmati J

Clin Nutr. 2019 May 10. pii: S0261-5614(19)30215-8. doi: 10.1016/j.clnu.2019.05.004. [Epub ahead of print]

Abstract

BACKGROUND & AIMS:

The impact of combined omega-3 FAs and vitamin E supplementation on oxidative stress (OS) has been evaluated in several studies. However the results are inconsistent. Therefore, we performed a systematic review and meta-analysis to assess the role of omega-3 FAplus vitamin E on anti-oxidant and OS parameters.

METHODS:

We searched five databases (PubMed, Embase, Web of Sciences, Scopus and the Cochrane Central Register of Controlled Trials) from inception until March 15th 2018 for RCT covering OS parameters combined with omega-3 FAs and vitamin E. The effect of omega-3 FAs plus vitamin E combination on OS factors was determined as the standardized mean difference (SMD) calculated according to DerSimonian and Laird for the random effects model.

RESULTS:

Nine articles were included in our analyses, significant improvements were observed in trials supplementing with omega-3 FAs plus vitamin E vs placebo for total antioxidant capacity (TAC) (SMD=0.63, 95%CI: 0.31 to 0.95, P<0.001) and nitric oxide (NO) (SMD=0.55, 95%CI: 0.23 to 0.87, P<0.001). Significant reduction was observed for malondialdehyde (MDA) (SMD: -0.48, 95%CI: -0.68 to -0.28, P<0.001). However, the results of meta-analysis did not show a significant difference in levels of glutathione (GSH) (SMD=0.34, 95%CI: -0.07 to 0.75, P=0.10), superoxide dismutase (SOD) activity (SMD: 0.07, 95% CI: -0.58 to 0.73, P=0.82) and Catalase (CAT) activity (SMD: 0.74, 95% CI: -0.30 to 1.79, P=0.16).

CONCLUSION:

Co-supplementation with omega-3 FAs and vitamin E increases the levels of NO and TAC, while MDA levels decrease compared to placebo. However, the results showed no significant alterations on GSH concentrations, CAT, and SOD activities.

Matsuo K, Watanabe T, Takenaka A

Physiol Behav. 2019 May 4;207:64-72. doi: 10.1016/j.physbeh.2019.04.026. [Epub ahead of print]

Abstract

It has been reported that the degree of anxiety-like behavior differs between inbred strains of mice, and that this phenomenon was linked to the expression levels of the oxidative stress-related genes glyoxalase 1 (Glo1) and glutathione reductase 1 (Gsr) in the brain. Therefore, we investigated whether antioxidative activity in the brain affects the Glo1 and Gsr mRNA expressions and strain-dependent anxiety-like behavior using mice fed different amounts of vitamin E. First, we measured brain Glo1 and Gsr mRNA levels and evaluated the anxiety-like behaviors presented by C57BL/6J (B6) and DBA/2C (D2) mice. We demonstrated that D2 mice presented both significantly elevated Glo1 and Gsr mRNA levels as well as more prominent anxiety-like behavior in elevated plus-maze and open field tests. Next, we fed mice from these two strains either a control, vitamin E-free, or vitamin E-supplemented diet for four weeks. Plasma, liver, and brain α-tocopherolconcentrations changed in a dose-dependent manner. However, neither brain Glo1 and Gsr mRNA levels nor anxiety-like behavior were affected by dietary vitamin E intake. These results demonstrated that while strain-dependent anxiety-like behavior in mice was related to oxidative stress-related gene expression, the regulatory mechanisms for these genes and anxiety-like behaviors were independent of antioxidative activity in the brain. Strain-dependent differences of the anxiety in mice are probably related to the anxiolytic effects of methylglyoxal, a substrate for Glo1 and Gsr.

Casati M, Boccardi V, Ferri E, Bertagnoli L, Bastiani P, Ciccone S, Mansi M, Scamosci M, Rossi PD, Mecocci P, Arosio B

Aging Clin Exp Res. 2019 May 3. doi: 10.1007/s40520-019-01209-3. [Epub ahead of print]

Abstract

BACKGROUND:

Vitamin E represents a potent antioxidant and anti-inflammatory system, playing a role in Alzheimer’s disease (AD). Different plasma concentrations of the forms of vitamin E are observed in AD compared to cognitively healthy subjects.

AIM:

Since these modifications may modulate the markers of oxidative stress and cellular aging, we aim to explore the relationship between vitamin E forms and leukocyte telomere length (LTL) in AD.

METHODS:

53 AD subjects and 40 cognitively healthy controls (CTs) were enrolled. The vitamin E forms (α-, β-, γ- and δ-tocopherol, α-, β-, γ- and δ-tocotrienol), the ratio of α-tocopherylquinone/α-tocopherol and 5-nitro-γ-tocopherol/γ-tocopherol (markers of oxidative/nitrosative damage) and LTL were measured.

RESULTS AND DISCUSSION:

Regression model was used to explore the associations of vitamin E forms and LTL with AD. The interaction of LTL in the association between vitamin E forms and AD was tested. AD subjects showed significantly lower concentrations of α-, β-, γ- and δ-tocopherol, α- and δ-tocotrienol, total tocopherols, total tocotrienols and total vitamin E compared to CTs. AD subjects showed higher values of nitrosative/oxidative damage. The adjusted analyses confirmed a significant relationship of AD with plasma concentrations of α- and β-tocopherols, δ-tocotrienol, total tocopherols, total tocotrienol, total vitamin E and oxidative/nitrosative damage. However, nitrosative damage was significantly associated with AD only in subjects with higher LTL and not in those expressing marked cellular aging.

CONCLUSIONS:

Our study confirms the role of vitamin E in AD pathology and indicates that nitrosative damage influences the association with AD only in subjects characterized by longer LTL.

Ibrahim MA, Bakhaat GA, Tammam HG, Mohamed RM, El-Naggar SA

Biomed Pharmacother. 2019 May;113:108731. doi: 10.1016/j.biopha.2019.108731. Epub 2019 Mar 6.

Abstract

BACKGROUND:

Cisplatin (CP) has been used in wide range for cancer treatment. Although nephrotoxicity of CP was the main complication, cardiotoxicity has been reported.

OBJECTIVES:

This study investigates the protective role of green tea extract (GTE) and vitamin E (Vit-E) against CP-induced cardiotoxicity, and assesses their impact on CP antitumor efficacy.

MATERIALS AND METHODS:

Forty-eight male albino Balb/c mice were randomly divided into six groups, 8 per/group (Gp) were included. Gp1 served as control; Gp2 and Gp3 received oral GTE (400 mg/kg) and Vit-E (100 mg/kg) for 30 consecutive days respectively. Gp4 had received CP (7 mg/kg i.p.) once on the 27th day; Gp5 had received GTE (400 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Gp6 had received Vit-E (100 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Blood and tissues samples were harvested for biochemical and histopathological investigations. To evaluate the effect of GTE and Vit-E on the antitumor efficacy of CP, 49 female albino mice were inoculated intraperitoneally by Ehrlich ascetic carcinoma -cells (2 × 10⁶/mouse) then treated with none, corn oil, CP, CP/GTE, CP/Vit-E, GTE or Vit-E.

RESULTS:

CP injection significantly increased Troponin I, CPK, CK-MB, malondialdehyde (MDA), and nitric oxide (NO) levels, while glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase levels were significantly reduced with disruption of cardiac muscle fibers, loss of striations, absence of intercalated disc, and the nuclei are pyknotic. Treatment with GTE and Vit-E improve the biochemical and histological parameters. Treatment with CP alone led to eradication of the tumor cells from the tumor-bearing mice. However, co-administration of GTE or Vit-E orally with CP did not interfere with its therapeutic effects.

CONCLUSION:

Treatment with GTE and Vit-E significantly ameliorated the CP cardiotoxicity and improved the myocardial histopathological architecture. GTE and Vit-E may be combined with CP to alleviate cardiotoxicity in cancer chemotherapy without interfering with its antitumor activity.

Erdemli Z, Erdemli ME, Turkoz Y, Gul M, Yigitcan B, Gozukara Bag H

Andrologia. 2019 Apr 17:e13292. doi: 10.1111/and.13292. [Epub ahead of print]

Abstract

Thirty rats, with confirmed pregnancies by vaginal smear, were divided into five groups, each including six rats, as the Control, Corn Oil, Vitamin E, Acrylamide, Vitamin E + Acrylamide groups. The births were monitored on the 21st day to select the male rats, and the selected male rats were decapitated at the end of the 8th week. Oxidant-antioxidant parameters, serum hormone levels and histopathological examinations were performed on testis tissues of the rats. It was found that acrylamide (AA) negatively affected the serum hormone levels (Total Testosterone, Progesterone, FSH, LH, Estradiol), oxidant-antioxidant parameters in the tissues (MDA, GSH, NO, SOD, CAT, TAS, TOS) (p < 0.05) and the histological findings (the Johnson’s score, seminiferous tubule diameter, histopathological images), and Vitamin Eadministration resulted with an increase in the total testosterone, progesterone, FSH, LH, GSH, TAS, NO, SOD, CAT levels (p < 0.05) and an improvement in histopathological findings. Currently, it is almost inevitable to be exposed to food-induced AA toxicity and such toxicity is likely to cause lifelong damage. It was concluded that Vitamin E was able to present a protective effect in the testis tissue against AA toxicity; however, further studies are necessary.

Alzoubi KH, Hasan ZA, Khabour OF, Mayyas FA, Al Yacoub ON, Banihani SA, Alomari MA, Alrabadi NN

Physiol Behav. 2019 Apr 13;206:200-205. doi: 10.1016/j.physbeh.2019.04.011. [Epub ahead of print]

Abstract

There is increasing evidence that oxidative stress is a causal factor in different neurodegenerative disorders such as Alzheimer’s disease and epilepsy. High-fat diet (HFD) has been shown to induce oxidative stress and neuronal damage that may increase susceptibility to seizures. The present study was undertaken to investigate the relationships between vitamin E, a potent antioxidant, HFD, and chemically induced seizures, using the PTZ seizure model in rats. Animals were randomly assigned into four groups: control, HFD, vitamin E (Vit E), and high-fat diet with vitamin E (HFD + Vit E) group. Vitamin E and/or HFD were administered to animals for 6 weeks. Thereafter, PTZ seizure threshold was measured in control and treated rats, and different brain regions were analyzed for levels of oxidative stress biomarkers. Current results revealed a significant reduction in PTZ seizure threshold in rats consuming HFD, which could be prevented by vitamin E supplement. Alongside, vitamin E supplement prevented HFD induced changes in oxidative stress biomarkers and capacity enzymes. Therefore, current results suggest that prolonged consumption of HFD increases susceptibility to PTZ induced seizures, which may be related to HFD induced oxidative stress. This increase in the PTZ susceptibility could be prevented by the administration of vitamin E, probably through its antioxidant effect, particularly at the brain hippocampal region.