α-Tocopherol protected against cobalt nanoparticles and cocl2 induced cytotoxicity and inflammation in Balb/3T3 cells

Yan X, Liu Y, Xie T, Liu F

Immunopharmacol Immunotoxicol. 2018 Jan 19:1-7. doi: 10.1080/08923973.2018.1424901. [Epub ahead of print]

Abstract

CONTEXT:

Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and cobalt ions (Co²⁺) are the most serious adverse effect in the patients with metal-on-metal hip prostheses. Therefore, an urgent need exists for the identification of the mechanisms and the development of therapeutic strategies to limit it.

OBJECTIVE:

We aimed to explore the mechanisms of cytotoxicity of CoNPs and Co²⁺ and developed strategies to reduce this cytotoxicity with α-tocopherol treatment.

METHODS:

To evaluate the protective effect of α-tocopherol, Balb/3T3 cells were pretreated with 10 μM α-tocopherol for 24 h. The cells were then exposed to different concentrations of CoNPs and Co²⁺ for 12 h, 24 h and 48 h. The cell viabilities, reactive oxygen species (ROS), inflammatory cytokines and MAP kinase (MAPK) levels were measured.

RESULTS:

CoNPs and Co²⁺ can induce the increase of ROS and inflammatory cytokines in Balb/3T3 cells, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, α-tocopherol pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co²⁺, decrease ROS production and decrease levels of inflammatory cytokines in Balb/3T3 cells. Additionally, MAPK pathway may be involved in the protection of α-tocopherol against cytotoxicity induced by CoNPs and Co²⁺ in vitro.

CONCLUSIONS:

Our results provide new insights into the potential therapeutic use of α-tocopherol in the prevention and treatment of various oxidative- or inflammatory stress-related inflammation and injuries.

Vineetha RC, Binu P, Arathi P, Nair RH

Toxicol Mech Methods. 2018 Jan 18:1-8. doi: 10.1080/15376516.2017.1422578. [Epub ahead of print]

Abstract

Arsenic trioxide (As₂O₃) is a potent drug for the treatment of acute promyelocytic leukemia (APL) and has achieved remarkable remissions in patients. Unfortunately, clinical reports have shown that the treatment is associated with cardiotoxicity. Many efforts have been made to mitigate drug-mediated cardiac damage using naturally occurring antioxidant compounds possessing free radical scavenging activity. The present investigation aims to explore protective role of L-ascorbic acid (L-AA) and α-tocopherol (α-TOC) from As₂O₃-induced oxidative stress in H9c2 cardiomyocytes through the evaluation of Nrf2 (nuclear factor erythroid 2-related factor 2) and Bcl-2 (B-cell lymphoma 2) transcription factors. The in vitro study was conducted using H9c2 cardiomyocytes. The evaluation of total antioxidant capacity, mitochondrial membrane potential, cellular calcium concentration and reactive oxygen species generation was performed. Oxidative stress (Nrf2) and anti-apoptotic (Bcl2) signaling indicators were measured by reverse transcriptase polymerase chain reaction. A depletion of the total antioxidant capacity and mitochondrial transmembrane potential were observed in As₂O₃-treated cardiomyocytes. In addition, the cellular calcium concentration and ROS generation were found to be increased on treatment with As₂O₃ with the alterations in the activity of transcription factors, Nrf2 and Bcl2. Co-treatment of antioxidant vitamins with As₂O₃ resulted in a significant reversal of oxidative stress and alteration on the antioxidant defense through the activation of Nrf2 and Bcl2. L-AA and α-TOC alleviates As₂O₃-induced oxidative stress in cardiac cells by activating Nrf2 and Bcl2 transcription factors that results in increased cell survival and prevents apoptosis.

Kancheva VD, Slavova-Kazakova AK, Angelova SE, Kumar P, Malhotra S, Singh BK, Saso L, Prasad AK, Parmar VS

J Sci Food Agric. 2018 Jan 18. doi: 10.1002/jsfa.8892. [Epub ahead of print]

Abstract

BACKGROUND:

Coumarin derivatives possess a wide range of biological activities. By functionalization of the parent coumarin skeleton that has neither antioxidant nor biological activity a series of new bio-antioxidants has been designed.

RESULTS:

New antioxidant compositions (equimolar binary and ternary mixtures) of eight 4-methylcoumarins and three related compounds have been tested and different effects between the individual components have been observed: positive effect (synergism), summary effect (additivism) and negative effect (antagonism). Higher oxidative stability of lipid substrate was obtained in presence of the new antioxidant compositions of studied compounds with DL-α-tocopherol and L-ascorbic acid. The role of each component in the antioxidant compositions of ternary mixtures has been identified by using new equations composed by us.

CONCLUSIONS:

All the ternary mixtures demonstrate synergism as a result of a continuous regeneration of DL-α-tocopherol from the studied antioxidants and L-ascorbic acid. Theoretical calculations have been probed in the prediction of the expected effects between the individual components in a double mixture.

Damiano S, Montagnaro S, Puzio MV, Severino L, Pagnini U, Barbarino M, Cesari D, Giordano A, Florio S, Ciarcia R

J Cell Biochem. 2018 Jan 18. doi: 10.1002/jcb.26686. [Epub ahead of print]

Abstract

In clinical practice for the treatment of chronic myeloid leukemia, second generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL and Src family kinase were developed to clinically overcome imatinib resistance. In this study we wanted to test the ability of some antioxidants such Resveratrol (RES) or a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) or δ-tocotrienol (δ-TOCO) to interact with DAS and NIL on viability, reactive oxygen species (ROS) production, lipid peroxidation and apoptosis. To test the possible mechanisms of action of such antioxidants, we utilized N-acetyl-L-cysteine (NAC) a specific inhibitor ROS production or PP1 a specific Src tyrosine kinase inhibitor or BAPTA a specific chelator of intracellular calcium. Our data demonstrated: 1) RES, rMnSOD, δ-TOCO and NAC, at dose used, significantly reduced the intracellular levels of MDA induced by DAS or NIL 2) RES, rMnSOD and δ-TOCO increased the intracellular ROS levels. 3) The increase ROS levels is related to higher levels of oligonucleosomesi induced by DAS and NIL and that NAC significantly reduced this activity. Interestingly, our data showed that apoptotic activity of DAS and NIL have significantly increased the production of oligonucleosomes by triggering excessive ROS generation as well as functionality of SERCA receptors.

Soares-Weiser K, Maayan N, Bergman H

Cochrane Database Syst Rev. 2018 Jan 17;1:CD000209. doi: 10.1002/14651858.CD000209.pub3. [Epub ahead of print]

Abstract

BACKGROUND:

Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) – a problem often seen as repetitive involuntary movements around the mouth and face. Vitamin E has been proposed as a treatment to prevent or decrease TD.

OBJECTIVES:

The primary objective was to determine the clinical effects of vitamin E in people with schizophrenia or other chronic mental illness who had developed antipsychotic-induced TD.The secondary objectives were:1. to examine whether the effect of vitamin E was maintained as duration of follow-up increased;2. to test the hypothesis that the use of vitamin E is most effective for those with early onset TD (less than five years) SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information.

SELECTION CRITERIA:

We included reports if they were controlled trials dealing with people with antipsychotic-induced TD and schizophrenia who remained on their antipsychotic medication and had been randomly allocated to either vitamin E or to a placebo, no intervention, or any other intervention.

DATA COLLECTION AND ANALYSIS:

We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who left early had no improvement. We assessed risk of bias and created a ‘Summary of findings’ table using GRADE.

MAIN RESULTS:

The review now includes 13 poorly reported randomised trials (total 478 people), all participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. There was no clear difference between vitamin E and placebo for the outcome of TD: not improved to a clinically important extent (6 RCTs, N = 264, RR 0.95, 95% CI 0.89 to 1.01, low-quality evidence). However, people allocated to placebo may show more deterioration of their symptoms compared with those given vitamin E (5 RCTs, N = 85, RR 0.23, 95% CI 0.07 to 0.76, low-quality evidence). There was no evidence of a difference in the incidence of any adverse effects (9 RCTs, N = 205, RR 1.21, 95% CI 0.35 to 4.15, very low-quality evidence), extrapyramidal adverse effects (1 RCT, N = 104, MD 1.10, 95% CI -1.02 to 3.22, very low-quality evidence), or acceptability of treatment (measured by participants leaving the study early) (medium term, 8 RCTs, N = 232, RR 1.07, 95% CI 0.64 to 1.80, very low-quality evidence). No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, outcomes designated important to patients. There is no trial-based information regarding the effect of vitamin E for those with early onset of TD.

AUTHORS’ CONCLUSIONS:

Small trials of limited quality suggest that vitamin E may protect against deterioration of TD. There is no evidence that vitamin E improves symptoms of this problematic and disfiguring condition once established. New and better trials are indicated in this under-researched area, and, of the many adjunctive treatments that have been given for TD, vitamin E would be a good choice for further evaluation.

El Hadi H, Vettor R, Rossato M

Antioxidants (Basel). 2018 Jan 16;7(1). pii: E12. doi: 10.3390/antiox7010012.

Abstract

Obesity is one of the major epidemics of this millennium, and its incidence is growing worldwide. Following the epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) has become a disease of increasing prevalence and a leading cause of morbidity and mortality closely related to cardiovascular disease, malignancies, and cirrhosis. It is believed that oxidative stress is a main player in the development and progression of NAFLD. Currently, a pharmacological approach has become necessary in NAFLD because of a failure to modify lifestyle and dietary habits in most patients. Vitamin E is a potent antioxidant that has been shown to reduce oxidative stress in NAFLD. This review summarizes the biological activities of vitamin E, with a primary focus on its therapeutic efficacy in NAFLD.

Marzagalli M, Moretti RM, Messi E, Marelli MM, Fontana F, Anastasia A, Bani MR, Beretta G, Limonta P

Sci Rep. 2018 Jan 12;8(1):587. doi: 10.1038/s41598-017-19057-4

Abstract

The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines. We observed that A375 (but not BLM) cells are able to form melanospheres and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. We also showed that a subpopulation of autofluorescent cells expressing the ABCG2 stem cell marker is present in the A375 spheroid culture. Based on these data, we investigated whether δ-TT might target melanoma CSCs. We demonstrated that melanoma cells escaping the antitumor activity of δ-TT are completely devoid of the ability to form melanospheres. In contrast, cells that escaped vemurafenib treatment show a higher ability to form melanospheres than control cells. δ-TT also induced disaggregation of A375 melanospheres and reduced the spheroidogenic ability of sphere-derived cells, reducing the expression of the ABCG2 marker. These data demonstrate that δ-TT exerts its antitumor activity by targeting the CSC subpopulation of A375 melanoma cells and might represent a novel chemopreventive/therapeutic strategy against melanoma.

Shen CL, Yang S, Tomison MD, Romero AW, Felton CK, Mo H

Osteoporos Int. 2018 Jan 12. doi: 10.1007/s00198-017-4356-x. [Epub ahead of print]

Abstract

Tocotrienols have shown bone-protective effect in animals. This study showed that a 12-week tocotrienol supplementation decreased concentrations of bone resorption biomarker and bone remodeling regulators via suppressing oxidative stress in postmenopausal osteopenic women.

INTRODUCTION:

Tocotrienols (TT) have been shown to benefit bone health in ovariectomized animals, a model of postmenopausal women. The purpose of this study was to evaluate the effect of 12-week TT supplementation on bone markers (serum bone-specific alkaline phosphatase (BALP), urine N-terminal telopeptide (NTX), serum soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and serum osteoprotegerin (OPG)), urine calcium, and an oxidative stress biomarker (8-hydroxy-2′-deoxyguanosine (8-OHdG)) in postmenopausal women with osteopenia.

METHODS:

Eighty-nine postmenopausal osteopenic women (59.7 ± 6.8 year, BMI 28.7 ± 5.7 kg/m²) were randomly assigned to three groups: (1) placebo (430 mg olive oil/day), (2) low TT (430 mg TT/day, 70% purity), and (3) high TT (860 mg TT/day, 70% purity). TT, an extract from annatto seed with 70% purity, consisted of 90% delta-TT and 10% gamma-TT. Overnight fasting blood and urine samples were collected at baseline, 6, and 12 weeks for biomarker analyses. Eighty-seven subjects completed the 12-week study.

RESULTS:

Relative to the placebo group, there were marginal decreases in serum BALP level in the TT-supplemented groups over the 12-week study period. Significant decreases in urine NTX levels, serum sRANKL, sRANKL/OPG ratio, and urine 8-OHdG concentrations and a significant increase in BALP/NTX ratio due to TT supplementation were observed. TT supplementation did not affect serum OPG concentrations or urine calcium levels throughout the study period. There were no significant differences in NTX level, BALP/NTX ratio, sRANKL level, and sRANKL/OPG ratio between low TT and high TT groups.

CONCLUSIONS:

Twelve-week annatto-extracted TT supplementation decreased bone resorption and improved bone turnover rate via suppressing bone remodeling regulators in postmenopausal women with osteopenia. Such osteoprotective TT’s effects may be, in part, mediated by an inhibition of oxidative stress.