Proteomic Changes in Mouse Spleen after Radiation-Induced Injury and its Modulation by Gamma-Tocotrienol

Cheema AK, Byrum SD, Sharma NK, Altadill T, Kumar VP, Biswas S, Balgley BM, Hauer-Jensen M, Tackett AJ, Ghosh SP

Radiat Res. 2018 Aug 2. doi: 10.1667/RR15008.1. [Epub ahead of print]

Abstract

Gamma-tocotrienol (GT3), a naturally occurring vitamin E isomer, a promising radioprotector, has been shown to protect mice against radiation-induced hematopoietic and gastrointestinal injuries. We analyzed changes in protein expression profiles of spleen tissue after GT3 treatment in mice exposed to gamma radiation to gain insights into the molecular mechanism of radioprotective efficacy. Male CD2F1 mice, 12-to-14 weeks old, were treated with either vehicle or GT3 at 24 h prior to 7 Gy total-body irradiation. Nonirradiated vehicle, nonirradiated GT3 and age-matched naïve animals were used as controls. Blood and tissues were harvested on days 0, 1, 2, 4, 7, 10 and 14 postirradiation. High-resolution mass-spectrometry-based radioproteomics was used to identify differentially expressed proteins in spleen tissue with or without drug treatment. Subsequent bioinformatic analyses helped delineate molecular markers of biological pathways and networks regulating the cellular radiation responses in spleen. Our results show a robust alteration in spleen proteomic profiles including upregulation of the Wnt signaling pathway and actin-cytoskeleton linked proteins in mediating the radiation injury response in spleen. Furthermore, we show that 24 h pretreatment with GT3 attenuates radiation-induced hematopoietic injury in the spleen by modulating various cell signaling proteins. Taken together, our results show that the radioprotective effects of GT3 are mediated, via alleviation of radiation-induced alterations in biochemical pathways, with wide implications on overall hematopoietic injury.

Montagnani Marelli M, Marzagalli M, Fontana F, Raimondi M, Moretti RM, Limonta P

J Cell Physiol. 2018 Aug 1. doi: 10.1002/jcp.27075. [Epub ahead of print]

Abstract

Vitamin E is composed of two groups of compounds: α-, β-, γ-, and δ-tocopherols (TPs), and the corresponding unsaturated tocotrienols(TTs). TTs are found in natural sources such as red palm oil, annatto seeds, and rice bran. In the last decades, TTs (specifically, γ-TT and δ-TT) have gained interest due to their health benefits in chronic diseases, based on their antioxidant, neuroprotective, cholesterol-lowering, anti-inflammatory activities. Several in vitro and in vivo studies pointed out that TTs also exert a significant antitumor activity in a wide range of cancer cells. Specifically, TTs were shown to exert antiproliferative/proapoptotic effects and to reduce the metastatic or angiogenic properties of different cancer cells; moreover, these compounds were reported to specifically target the subpopulation of cancer stem cells, known to be deeply involved in the development of resistance to standard therapies. Interestingly, recent studies pointed out that TTs exert a synergistic antitumor effect on cancer cells when given in combination with either standard antitumor agents (i.e., chemotherapeutics, statins, “targeted” therapies) or natural compounds with anticancer activity (i.e., sesamin, epigallocatechin gallate (EGCG), resveratrol, ferulic acid). Based on these observations, different TT synthetic derivatives and formulations were recently developed and demonstrated to improve TT water solubility and to reduce TT metabolism in cancer cells, thus increasing their biological activity. These promising results, together with the safety of TT administration in healthy subjects, suggest that these compounds might represent a new chemopreventive or anticancer treatment (i.e., in combination with standard therapies) strategy. Clinical trials aimed at confirming this antitumor activity of TTs are needed.

Kumar A, Sharma R, Rana D, Sharma N

Endocr Metab Immune Disord Drug Targets. 2018 Aug 1. doi: 10.2174/1871530318666180801144822. [Epub ahead of print]

Abstract

BACKGROUND AND OBJECTIVE:

α-Tocopherol is the active form of vitamin E which have various biological functions. However, the exact molecular mechanism of its action is not fully understood. Thus, the main objective of the current study is to determine the contribution of α-tocopherol in counteraction of the apoptogenic signaling pathways induced by deltamethrin in murine thymocytes and splenocytes.

METHODS AND RESULTS:

Deltamethrin (25 µM) induces apoptosis at 18 h through activation of reactive oxygen species, caspases and depletion of glutathione in thymocytes and splenocytes. MTT assay results have shown that α-tocopherol (10 and 50 µg/ml) when added along with Deltamethrin (25µM), increases the viability of thymocytes and splenocytes in a concentration-dependent manner. The α-tocopherol treatment reduces the early markers of cell death (ROS and caspase3 activation) significantly. Further, the depleted GSH by deltamethrin, has been also restored by α-tocopherol. At 18 h, α-tocopherol (50 µg/ml) significantly reduced the Deltamethrin induced cell death. In additional, phenotyping and cytokines assay have demonstrated that alpha-tocopherol significantly ameliorated the altered immune functions.

CONCLUSION:

These findings indicate that α-tocopherol shows immunoprotective effects in Deltamethrin induced splenic and thymic apoptosis by inhibiting oxidative stress and caspase-dependent apoptogenic pathways.

Amraoui W, Adjabi N, Bououza F, Boumendjel M, Taibi F, Boumendjel A, Abdennour C, Messarah M

Toxicol Res. 2018 Jul;34(3):231-239. doi: 10.5487/TR.2018.34.3.231. Epub 2018 Jul 15.

Abstract

Bisphenol A, an everywhere chemical, is applied as a plasticizer in polycarbonate plastics, which often used in our everyday products and in epoxy resins as protective coatings and linings for food and beverage cans for decades. Human exposure to BPA may lead to adverse effects by interfering with oestrogen receptors. Our present study was conducted to investigate the protective effects of selenium (Se) and vitamin E(Vit E) on BPA-induced damage in the liver of male rats. Animals were randomly divided into four groups: the first group received olive oil and served as control. The second group received both (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet). The third one treated orally by (10 mg/kg b.w.) of BPA. The last group received (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet) concomitantly with (10 mg/kg b.w.) BPA. Exposure to BPA for three weeks engendered a hepatic disorder. An increased AST and ALT enzymatic activity was noticed in BPA-treated group as compared to other groups. Furthermore, a change in glucose, cholesterol, LDL-C, HDL-C, albumin, and bilirubin level was remarkable. Moreover, exposure to BPA increased malondialdehyde levels while reduced gluthatione content was decreased in the liver homogenate. A decrease in glutathione peroxidase, glutathione s-transferase and catalase activities was observed in the same group. Administration of selenium and vitamin E through the diet in BPA treated rats ameliorated the biochemical parameters cited above. In addition, an improvement in activities of liver enzymes was recorded. The histological findings confirmed the biochemical results. The model of this study that we employed characterized the relationships between BPA-induced hepatotoxicity and its alleviation by natural antioxidants like selenium and vitamin E.

Chalouati H, Ben Sâad MM, Payrastre L

Toxicol Mech Methods. 2018 Jul 31:1-31. doi: 10.1080/15376516.2018.1506847. [Epub ahead of print]

Abstract

The protective effects of α-Tocopherol (vitamin E) on liver injury induced by hexachlorobenzene (HCB) were investigated in adult male rats of Wistar strain. Animals were randomly divided into six groups of eight rats each. Group 1 and 2 have received HCB, dissolved in olive oil, at a dose of 4 mg or 16 mg/kg b.w, respectively. Group 3 and 4 were treated by the same doses of HCB (4 mg and 16 mg/kg b.w) after 1h of pretreatment with α-tocopherol at a dose of 100 mg kg^-1 b.w. The other two groups served as controls; which received either olive oil only, a solvent of HCB, or α-tocopherol. A significant increase in hepatic lipid peroxidation (LPO) and GSH activity were observed following HCB administration. The activities of antioxidant enzymes like superoxide dismutase and catalase were significantly decreased while glutathione peroxidase was significantly increased following HCB administration. Similarly, a significant increase in plasma levels of various marker enzymes [aminotransferase (AST and ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] and a decrease of total protein level were observed. Pretreatment with vitamin E of HCB treated rats ameliorated all biochemical parameters to near normal values. Liver histological study confirmed biochemical parameters and the beneficial role of vitamin E.

Dong R, Yang Q, Zhang Y, Li J, Zhang L, Zhao H

Wei Sheng Yan Jiu. 2018 Jul;47(4):648-654.

Abstract

OBJECTIVE:

To systematically evaluate the levels of vitamin C, vitamin E and β-carotene in the plasma of Alzheimer’s disease( AD) patients.

METHODS:

In this study, literature of the levels of vitamin C, vitamin E and β-carotene in the plasma of AD patients were collected by retrieving the database of Pub Med, Science Direct, CNKI and Wan Fang( from they were built to July 2017).

RESULTS:

Meta-analysis result showed that, compared with the control group, the level of vitamin E in the plasma of AD patients declined significantly( SMD =-1. 49 μmol/L, 95% CI-2. 08–0. 89 μmol/L, P <0. 001). However, no differences were determined in the levels of the plasma vitamin C and β-carotene between the two groups( vitamin C: SMD =-1. 43 μmol/L, 95% CI-3. 05-0. 19 μmol/L, P = 0. 083; β-carotene: SMD =-0. 61 μmol/L, 95% CI-1. 40-0. 18 μmol/L, P = 0. 131).

CONCLUSION:

Increasing vitamin E level in the plasma through vitamin E riched diet may be useful to prevent AD. However it is not yet believed the benefical role on AD to increase vitamin C and β-carotene.

Okamura Y, Omori A, Asada N, Ono A

J Clin Biochem Nutr. 2018 Jul;63(1):50-57. doi: 10.3164/jcbn.17-96. Epub 2018 Apr 3.

Abstract

The purpose of this study was to investigate the influence of vitamins C and E on the toxic action of alcohol in rat liver regeneration. Male Sprague-Dawley rats subjected to 70% partial hepatectomy were divided into five groups (Groups 1 to 5). Rats in Groups 2 to 5 were only provided alcohol for drinking. Additionally, vitamin C, vitamin E, and vitamin C in combination with vitamin E were administered to Groups 3, 4, and 5, respectively. Alcohol inhibits liver regeneration, resulting in an increase in free radicals produced by alcohol metabolism and thus causing cellular damage and altering liver function. During liver regeneration, vitamins C and E significantly ameliorated liver injury from alcohol administration by reducing hepatic lipid peroxidation. Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus may be more effective in combination than either vitamin alone against alcohol-mediated toxic effects during liver regeneration.

Najafpour A, Azizizadeh H

Bull Emerg Trauma. 2018 Jul;6(3):207-216. doi: 10.29252/beat-060304.

Abstract

OBJECTIVE:

To investigate effects of intraperitoneally administration of α-tocopherol loaded nanoparticles (TNP) on ischemia-reperfusion injury in ovaries.

METHODS:

Thirty-five healthy female Wistar rats ~250g were randomized into seven experimental groups (n = 5): Group SHAM: The rats underwent only laparotomy. Group Ischemia: A 3- hour ischemia only. Group I/R: A 3-hour ischemia and a 3-hour reperfusion. Group I/T: A 3-hour ischemia only and 100 mg/kg intraperitoneal administration (IP) of α-tocopherol 2.5 hours after induction of ischemia. Group I/R/T: A 3-hour ischemia, a 3-hour reperfusion and 100 mg/kg IP of α-tocopherol 2.5 hours after induction of ischemia. Group I/TNP: A 3-hour ischemia only and 1 mg/kg IP of TNP 2.5 hours after induction of ischemia. Group I/R/TNP: A 3-hour ischemia, a 3-hour reperfusion and 1 mg/kg IP of TNP 2.5 hours after induction of ischemia.

RESULTS:

Animals treated with αTNP showed significantly ameliorated development of ischemia and reperfusion tissue injury compared to those of other groups (p=0.001). The significant higher values of SOD, tGSH, GPO, GSHRd and GST were observed in I/R/NC animals compared to those of other groups (p=0.001). Damage indicators (NOS, MDA, MPO and DNA damage level) were significantly lower in I/R/NC animal compared to those of other groups (p=0.001).

CONCLUSION:

Intraperitoneal administration of TNP could be helpful in minimizing ischemia-reperfusion injury in ovarian tissue exposed to ischemia.

Chou CC, Sung YC, Davison G, Chen CY, Liao YH

Int J Med Sci. 2018 Jul 30;15(11):1217-1226. doi: 10.7150/ijms.26340. eCollection 2018.

Abstract

Background: Exercise-induced muscle damage during intensive sport events is a very common issue in sport medicine. Therefore, the purpose is to investigate the effects of short-term high-dose vitamin C and E supplementation on muscle damage, hemolysis, and inflammatory responses to simulated competitive Olympic Taekwondo (TKD) matches in elite athletes. Methods: Using a randomized placebo-controlled and double-blind study design, eighteen elite male TKD athletes were weight-matched and randomly assigned into either a vitamin C and E group (Vit C+E; N = 9) or placebo group (PLA; N = 9). Vit C+E or PLA supplements were taken daily (Vit C+E: 2000 mg/d vitamin C; 1400 U/d vitamin E) for 4 days (3 days before and on competition day) before taking part in 4 consecutive TKD matches on a single day. Plasma samples were obtained before each match and 24-hours after the first match for determination of markers of muscle damage, hemolysis, and systemic inflammatory state. Results: Myoglobin was lower in the Vit C+E group, compared to PLA, during the match day (area under curve, AUC -47.0% vs. PLA, p = 0.021). Plasma creatine kinase was lower in the Vit C+E group (AUC -57.5% vs. PLA, p = 0.017) and hemolysis was lower in the Vit C+E group (AUC -40.5% vs. PLA, p = 0.034). Conclusions: We demonstrated that short-term (4-days) vitamin C and E supplementation effectively attenuated exercise-induced tissue damage and inflammatory response during and after successive TKD matches.

Shen CL, Kaur G, Wanders D, Sharma S, Tomison MD, Ramalingam L, Chung E, Moustaid-Moussa N, Mo H, Dufour JM

Sci Rep. 2018 Jul 27;8(1):11377. doi: 10.1038/s41598-018-29063-9.

Abstract

Diabetes is a risk factor for osteoporosis. Annatto-extracted tocotrienols (TT) have proven benefits in preserving bone matrix. Here, we evaluated the effects of dietary TT on glucose homeostasis, bone properties, and liver pro-inflammatory mRNA expression in high-fat diet (HFD)-induced type 2 diabetic (T2DM) mice. 58 male C57BL/6 J mice were divided into 5 groups: low-fat diet (LFD), HFD, HFD + 400 mgTT/kg diet (T400), HFD + 1600 mgTT/kg diet (T1600), and HFD + 200 mg metformin/kg (Met) for 14 weeks. Relative to the HFD group, both TT-supplemented groups (1) improved glucose homeostasis by lowering the area under the curve for both glucose tolerance and insulin tolerance tests, (2) increased serum procollagen I intact N-terminal propeptide (bone formation) level, trabecular bone volume/total volume, trabecular number, connectivity density, and cortical thickness, (3) decreased collagen type 1 cross-linked C-telopeptide (bone resorption) levels, trabecular separation, and structure model index, and (4) suppressed liver mRNA levels of inflammation markers including IL-2, IL-23, IFN-γ, MCP-1, TNF-α, ITGAX and F4/80. There were no differences in glucose homeostasis and liver mRNA expression among T400, T1600, and Met. The order of osteo-protective effects was LFD ≥T1600 ≥T400 = Met >HFD. Collectively, these data suggest that TT exerts osteo-protective effects in T2DM mice by regulating glucose homeostasis and suppressing inflammation.