The modifying effect of nutritional factors on the association between IL1-β single nucleotide polymorphism and serum CXCL10 levels in young Canadian adults

Li X, Jarosz AC, El-Sohemy A, Badawi A

Nutr Health. 2020 Mar 31:260106020912945. doi: 10.1177/0260106020912945. [Epub ahead of print]

Abstract

BACKGROUND:

Genetic and nutritional factors play an important role in inflammatory response and diseases. CXCL10 is a critical biomarker that is involved in multiple inflammatory diseases, and elevated levels of CXCL10 have been associated with the development of several chronic and infectious diseases. In contrast, micronutrients can attenuate inflammatory responses. Single nucleotide polymorphisms in the pro-inflammatory cytokine genes such as IL-1β at rs16944 contributed to a number of inflammatory disorders and may substantiate the convergance between chronic and infectious diseases.

AIM:

This study aims to identify the modifying effect of nutritional factors on the association between IL-1β genotypes and CXCL10 levels.

METHODS:

Participants (N = 386) were healthy males and females from the Toronto Nutrigenomics and Health study recruited from the University of Toronto. Levels of micronutrients and inflammatory markers were measured in plasma. IL-1β genotypes were extracted from the Affymetrix 6.0 SNP chip.

RESULTS:

CXCL10 levels were not different across different IL-1β genotypes. Among those with the GA genotype, elevated CXCL10 levels were observed with higher than median ascorbic acid (β = 0.004 ± 0.002, P = 0.047) or higher than median vitamin D status (β = 0.003 ± 0.002, P = 0.044). Among participants with the AA genotype, subjects with low α-tocopherol status had elevated levels of CXCL10 (β = -0.016 ± 0.007, P = 0.012).

CONCLUSION:

The association between IL-1β rs16944 genotype and CXCL10 levels was modified by the levels of ascorbic acid, α-tocopherol and vitamin D. These findings may aid in understanding the combined effect of genetic and dietary factors in the development of various infectious and chronic diseases in which IL-1β and CXCL10 may play an etiological role.

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Aberrant expression of placental-like alkaline phosphatase in chronic myeloid leukemia cells in vitro and its modulation by vitamin E

Shvachko LP, Zavelevich MP, Gluzman DF, Telegeev GD

Exp Oncol. 2020 Mar;42(1):31-34.

Abstract

Placental-like alkaline phosphatase (PLAP) is expressed by many tumors and can be detected in sera of patients with various cancers. Its aberrant expression has been considered to be potentially useful as tumor marker. However, the biological background of the role of this aberrant alkaline phosphatase (AP) in cancer is still unclear. The expression of various forms of AP in cells of chronic myeloid leukemia (CML) has not yet been studied.

AIM:

To analyze the expression patterns of various AP forms in cells originated from CML patients in blast crisis and to modify their expression by vitamin E.

MATERIALS AND METHODS:

RNA extracted from leukemic cells was converted to cDNA and real-time reverse transcription polymerase chain reaction was performed using SYBR Green protocol with primers to tissue non-specific alkaline phosphatase (TNAP), intestinal alkaline phosphatase and CCAAT-enhancer-binding proteins alpha (C/EBPα). To analyze the modulation of expression of APs and C/EBPα, CML cells were incubated with 100 µM vitamin E.

RESULTS:

We have observed the aberrant expression of mRNA intestinal alkaline phosphatase in CML cells that upon sequencing demonstrated the significant alignment with PLAP sequence while no gene homology with tissue placental alkaline phosphatase (PAP) was revealed. Vitamin E decreases mRNA PLAP expression and increases mRNA TNAP expression. Moreover, along with down-regulation of aberrant PLAP and up-regulation of TNAP, vitamin E increases C/EBPα mRNA expression.

CONCLUSION:

The loss of TNAP in CML may contribute to pathogenesis of this disease. PLAP may be considered as a putative target in differentiation therapies in myeloid neoplasms. Our findings suggest the potential role of vitamin E as the inducer of differentiation potential of leukemic cells in CML.

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Inhibition of lipid peroxidation during the reproductive period extends the lifespan of Caenorhabditis elegans

Sakamoto T, Maebayashi K, Tsunoda Y, Imai H

J Clin Biochem Nutr. 2020 Mar;66(2):116-123. doi: 10.3164/jcbn.19-51. Epub 2020 Jan 31.

Abstract

Glutathione peroxidase 4 (GPx4) is a unique antioxidant enzyme that directly reduces the phospholipid hydroperoxides (PLOOH) generated in biomembranes using glutathione as the reductant. We have previously reported that the Caenorhabditis elegans gpx-quad mutant, which lacks all homologous genes of GPx4 has a reduced lifespan compared with the wild-type. However, the mechanisms underlying the lifespan reduction remain unclear. By monitoring the change in PLOOH production with age, we found that PLOOH was elevated in the gpx-quad mutants compared with the wild-type during the reproductive period. Administration of vitamin E not only reduced the PLOOH content but also prolonged the lifespan of the gpx-quad mutants. In contrast, vitamin C did not extend the lifespan of the gpx-quad mutants. Interestingly, we found that the inhibition of lipid peroxidation by vitamin E during 5 to 10 days after hatching is important to extend the lifespan of C. elegans. These results suggest that production of PLOOH during the reproductive period strongly influences the lifespan of C. elegans.

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pH-sensitive small molecule nanodrug self-assembled from amphiphilic vitamin B6-E analogue conjugate for targeted synergistic cancer therapy

Yan G, Chen R, Xiong N, Song J, Wang X, Tang R

Colloids Surf B Biointerfaces. 2020 Mar 28;191:111000. doi: 10.1016/j.colsurfb.2020.111000. [Epub ahead of print]

Abstract

To promote the targeted cancer therapy, the pH-sensitive small molecule nanodrug self-assembled from amphiphilic vitamin B6-E analogue conjugate was successfully constructed. Herein, water-soluble vitamin B6 with pKa (5.6) was chemically conjugated to lipid-soluble vitamin E succinate (α-TOS), which showed selective cancer cell killing ability and this amphiphilic small molecule vitamin conjugate could self-assemble to be free nanoparticles (NPs) and doxorubicin-loaded NPs (α-TOS-B6-NPs-DOX). The small molecule nanodrugs could perform the following characteristic: (i) stability in the sodium dodecyl sulfonate (SDS) solution and long-term storage stability in PBS via surface negative charge; (ii) tumor accumulation by enhanced penetration and retention (EPR) effect; (iii) improved cellular internalization by means of vitamin B6 transporting membrane carrier (VTC); and (iv) facilitating endosomal escape and rapid drug release for synergistic toxicity to tumor cells via charge reversal and ester hydrolysis at intracellular pH and/or esterase. Moreover, α-TOS-B6-NPs-DOX exhibited long blood circulation stability and significant tumor accumulation and inhibition with the decreased side effects in vivo. Thus, the pH-sensitive small molecule nanodrug self-assembled from amphiphilic vitamin B6-E analogue conjugate could be the potential drug carriers in targeted synergistic cancer therapy.

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Oxidative stress, hematological and biochemical alterations induced by sub-acute exposure to fipronil (COACH®) in albino mice and ameliorative effect of selenium plus vitamin E

Abouelghar GE, El-Bermawy ZA, Salman HMS

Environ Sci Pollut Res Int. 2020 Mar;27(8):7886-7900. doi: 10.1007/s11356-019-06579-9. Epub 2019 Dec 30.

Abstract

Fipronil (FIP) is a highly effective, broad-use insecticide that belongs to the phenylpyrazole chemical group. It is extensively used in the agriculture and veterinary medicine for controlling a wide variety of pests. Though FIP showed lower toxicity in vertebrates than in insects, it was recognized to have a variety of toxic effects in mammals. The present study was undertaken to evaluate FIP-induced alterations in the blood biochemical markers and oxidative stress parameters in male albino mice via oral sub-acute toxicity exposure. The possible ameliorative effect of the pretreatment with selenium plus α-tocopherol (vitamin E) against the harmful effects of FIP was also investigated. Mice in FIP-test groups were exposed to different sublethal doses, i.e., 1.43, 2.87, and 4.78 mg active ingredient (AI)/kg body weight (b.w.), equal to 1/100, 1/50, and 1/30 LD50 of FIP, respectively, for 28 days. Mice in the amelioration groups were orally administered with selenium + vitamin E (0.3 mg + 22.5 mg/kg b.w., respectively) 14 days prior to exposure to the higher dose (4.78 mg/kg) of FIP for another 14 days. Fipronil exposure at medium and high doses showed lowered values of red blood cell count (RBC), hematocrit (HCT), hemoglobin (HGB), white blood cell (WBC), and platelet (PLT) counts after 28-day exposure, compared to the control. All three doses caused significant increases in levels of liver-function biomarkers, i.e., aspartate amino transaminase (AST), alanine amino transaminase (ALT), alkaline phosphatase (ALP), cholesterol, and bilirubin levels compared to the control. Levels of biomarkers related to kidney functions, i.e., urea, uric acid, and creatinine, increased significantly than these of the control. Likewise, the oxidative stress indices, i.e., hydrogen peroxide (H2O2) and malondialdehyde (MDA), significantly increased at the higher and medium doses, while antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD), decreased significantly. On the other hand, prior administration of selenium + vitamin E in the FIP-exposed mice led to restore values of most hematological parameters nearly to these of the control. Also, the levels of AST, total protein, and creatinine seemed to be restored to the control values. Interestingly, pretreatment with selenium + vitamin E restored the levels of antioxidant enzymes, CAT and SOD, to the control values, whereas, oxidative stress indices, H2O2 and MDA, remained significantly high. It is our thought that the sublethal dose less than 1.43 mg/kg b.w. of commercial formulation of FIP (COACH® 200 SC) could be considered as no-observed-adverse-effect-level(NOAEL) under our present experimental conditions at short-term toxicity study. On the other hand, the higher sublethal doses, 4.78 and 2.87 mg/kg b.w., induced significant adverse effects in biomarkers and may be deleterious to human health following long-term exposure.

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Extraction of phytosterols and tocopherols from rapeseed oil waste by supercritical CO2 plus co-solvent: A comparison with conventional solvent extraction

Jafarian Asl P, Niazmand R, Yahyavi F

Heliyon. 2020 Mar 25;6(3):e03592. doi: 10.1016/j.heliyon.2020.e03592. eCollection 2020 Mar.

Abstract

In the present study, modified extraction methods using supercritical CO2 were investigated in order to obtain high-added value compounds from rapeseed oil deodorizer distillate and comparisons were done with modified Soxhlet extraction (solvent extraction + silica). For supercritical fluid extraction (SFE), the optimal extraction parameters were temperature of 40 °C, pressure of 350 bar (for phytosterols), 400 bar (for tocopherol), 5 wt% ethanol as co-solvent, and saponification pretreatment. The optimized SFE procedure led to the recovery of three main phytosterols (50 wt % β-sitosterol, 23.91 wt % Brassicasterol, and 36.25 wt % Campesterol) and only α-tocopherol. Moreover, there was no synergistic effect with saponification pretreatment + co-solvent and the efficiency and concentration of target compounds were less than supercritical CO2 + co-solvent. Also, comparative Data showed that the efficiency of phytosterols and tocopherols was approximately three times higher (p < 0.05) in SFE relative to modified Soxhlet extraction. Furthermore, the use of ethanol (5 wt %) as co-solvent, improved phytosterols and tocopherol efficiency and purity. The SFE technique offers various advantages over the modified Soxhlet extraction technique, including increasing the solubility of tocopherols and sterols by using CO2+ co-solvent, minimized usage of toxic organic solvents and increased purity of extracted products.

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Enhanced Antioxidative Defense by Vitamins C and E Consumption Prevents 7-Day High-Salt Diet-Induced Microvascular Endothelial Function Impairment in Young Healthy Individuals

Barić L, Drenjančević I, Mihalj M, Matić A, Stupin M, Kolar L, Mihaljević Z, Mrakovčić-Šutić I, Šerić V, Stupin A

J Clin Med. 2020 Mar 20;9(3). pii: E843. doi: 10.3390/jcm9030843.

Abstract

This study aimed to examine whether the oral supplementation of vitamins C and E during a seven-day high salt diet (HS; ~14 g salt/day) prevents microvascular endothelial function impairment and changes oxidative status caused by HS diet in 51 (26 women and 25 men) young healthy individuals. Laser Doppler flowmetry measurements demonstrated that skin post-occlusive reactive hyperemia (PORH), and acetylcholine-induced dilation (AChID) were significantly impaired in the HS group, but not in HS+C+E group, while sodium nitroprusside-induced dilation remained unaffected by treatments. Serum oxidative stress markers: Thiobarbituric acid reactive substances (TBARS), 8-iso prostaglandin-F2α, and leukocytes’ intracellular hydrogen peroxide (H2O2) production were significantly increased, while ferric-reducing ability of plasma (FRAP) and catalase concentrations were decreased in the HS group. All these parameters remained unaffected by vitamins supplementation. Matrix metalloproteinase 9, antioxidant enzymes Cu/Zn SOD and glutathione peroxidase 1, and leukocytes’ intracellular superoxide production remained unchanged after the protocols in both HS and HS+C+E groups. Importantly, multiple regression analysis revealed that FRAP was the most powerful predictor of AChID, while PORH was strongly predicted by both FRAP and renin-angiotensin system activity. Hereby, we demonstrated that oxidative dis-balance has the pivotal role in HS diet-induced impairment of endothelial and microvascular function in healthy individuals which could be prevented by antioxidative vitamins consumption.

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Oxidative stress and the antioxidant system in salivary glands of rats with experimental chronic kidney disease

Nogueira FN, Romero AC, Pedrosa MDS, Ibuki FK, Bergamaschi CT

Arch Oral Biol. 2020 Mar 20;113:104709. doi: 10.1016/j.archoralbio.2020.104709. [Epub ahead of print]

Abstract

OBJECTIVE:

This study aims to analyze the presence of oxidative stress and activity of the antioxidant system in the parotid and submandibular salivary glands of rats with Chronic Kidney Disease (CKD).

DESIGN:

Sixteen male wistar rats were divided into two groups (n = 8, each): control rats and rats with CKD. CKD was induced by 5/6 nephrectomy. Blood urea nitrogen and serum creatinine clearance were quantified. Malondialdehyde, superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, total antioxidant status, ascorbic acid, α-tocopherol, superoxide anion, and hydrogen peroxide concentrations were assessed.

RESULTS:

In CKD rats, blood urea nitrogen, serum creatinine, and proteinuria concentrations were increased, while creatinine clearance was reduced. In the submandibular gland, superoxide anion concentration was increased significantly (p < 0.05). Hydrogen peroxide and superoxide anion concentrations were reduced in the parotid gland. CKD rats presented increased malondialdehyde concentration, total antioxidant status, superoxide dismutase, and glutathione reductase activities only in the parotid gland (p < 0.05).

CONCLUSION:

Oxidative stress and changes in the antioxidant system were found in the parotid and submandibular salivary glands in an experimental model of CKD induced by 5/6 nephrectomy.

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Tocol Prophylaxis for Total-body Irradiation: A Proteomic Analysis in Murine Model.

Rosen E, Fatanmi OO, Wise SY, Rao VA, Singh VK

Health Phys. 2020 Mar 20. doi: 10.1097/HP.0000000000001221. [Epub ahead of print]

Abstract

The aim of this study was to analyze the changes in mouse jejunum protein expression in response to prophylactic administration of two promising tocols, γ-tocotrienol (GT3) and α-tocopherol succinate (TS), as radiation countermeasures before irradiation to elucidate the molecular mechanism(s) of their radioprotective efficacy. Mice were administered GT3 or TS (200 mg kg) subcutaneously 24 h prior to exposure to 11 Gy Co γ-radiation, a supralethal dose for mice. Jejunum was harvested 24 h post-irradiation. Results of the two-dimensional differential in-gel electrophoresis (2D-DIGE), coupled with mass spectrometry, and advanced bioinformatics tools suggest that the tocols have a corresponding impact on expression of 13 proteins as identified by mass spectrometry. Ingenuity Pathway Analysis (IPA) reveals a network of associated proteins involved in inflammatory response, organismal injury and abnormalities, and cellular development. Relevant signaling pathways including actin cytoskeleton signaling, RhoA signaling, and Rho family GTPase were identified. This study reveals the major proteins, pathways, and networks involved in preventing the radiation-induced injury in gut that may be contributing to enhanced survival.

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Pharmacokinetics and Pharmacodynamics of Ursodeoxycholic Acid in an Overweight Population With Abnormal Liver Function

Yoon S, Lee H, Ji SC, Yoon SH, Cho JY, Chung JY

Clin Pharmacol Drug Dev. 2020 Mar 19. doi: 10.1002/cpdd.790. [Epub ahead of print]

Abstract

Ursodeoxycholic acid (UDCA) is a secondary bile acid that is used to treat primary biliary cholangitis. Although UDCA has a hepatoprotective effect in some diseases, its benefit in nonalcoholic fatty liver disease (NAFLD) remains controversial. We aimed to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of UDCA in overweight subjects with elevated liver enzymes after multiple administrations of UDCA and compare these changes with vitamin E treatment. Overweight subjects (body mass index, 25-30 kg/m2 ) with elevated alanine aminotransferase (ALT) level (40-200 IU/L) were enrolled. Subjects received one of the following three 8-week treatments: UDCA 300 mg twice daily UDCA 300 mg twice daily for 4 weeks followed by UDCA 300 mg twice daily and metformin 500 mg twice daily for 4 weeks, and vitamin E 400 IU twice daily. PK and PD (liver function, lipid profiles, insulin sensitivity, and miR-122) analyses were performed. Thirty subjects were enrolled; 1 subject withdrew his consent during the study. The PK characteristics were similar to those of healthy volunteers. The ALT and miR-122 levels decreased in the UDCA groups, whereas the ALT and aspartate aminotransferase levels decreased in the vitamin E group. The lipid profiles and insulin sensitivity did not show significant changes among the groups. There was no serious adverse event, and the safety profiles were similar among the treatment groups. The liver enzyme and miR-122 levels were decreased by UDCA. Considering UDCA and vitamin E have a hepatoprotective effect and different mechanisms of action, combination therapy could be an option for NAFLD.

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