PMID: 

Int J Reprod Biomed (Yazd). 2019 Feb ;17(2). Epub 2019 Mar 19. PMID: 31435589

Abstract Title: 

Protective effect of vitamin E on oxidative stress and sperm apoptosis in diabetic Mice.

Abstract: 

Background: Generation of free radicals and oxidative stress are a major contributor to diabetes. These factors lead to the development of diabetic testicles disorders.Objective: In this study, the protective effect of vitamin E on functional disorders associated with diabetes induced oxidative stress in male reproductive systems has been investigated.Materials and Methods: Thirty-three adult male Mice were divided into control, diabetic, and untreated diabetic groups. Streptozotocin was used to induce diabetes. In the treated group, vitamin E was given to the Mice intraperitoneally for 30 days. Then, animals were anesthetized and sacrificed. Animal testicles were isolated and homogenized in phosphate buffer and used for measuring sperm count, motility and survival of sperm, MDA concentration and antioxidant capacity (TAC). Apoptosis was also performed with the TUNEL test.Results: The results of reduction (12.0398.11) TAC, MDA concentration (-28.52.58), sperm motility (unstable sperma= 86.47.48), sperm count (171.51), Sperm morphology (natural morphology= 49.6931.93) and abnormal morphology (9.7749.7) with increased oxidative damage. These changes were statistically significant in comparison with the control group for all variables other than MDA (p= 0.05). Treatment of vitamin E diabetic Mice improved the ability of antioxidants to prevent oxidative damage in the testicles, restore the sperm movement, and increase the number of normal sperm as well as TAC. The level of apoptosis in the treated group has decreased compared to the untreated group.Conclusion: Vitamin E protects the reproductive system against diabetes mellitus. Therefore, it was concluded that vitamin E may be a suitable agent for protecting the sperm and testicular parameters against undesirable effects of diabetes.

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PMID: 

Tunis Med. 2019 Jan ;97(1):100-105. PMID: 31535700

Abstract Title: 

Protective role of vitamin E against cadmium induced oxidative stress into the rat liver.

Abstract: 

INTRODUCTION: Cadmium (Cd) is a toxic heavy metal used in various industrial applications and therefore can cause, both by environmental or professional exposure, several damage in all body systems. The present study was developed to determine the toxic effect of high dose of Cd on the rat's liver as well as the putative protective effect of vitamin E.METHODS: During the experiment, rats were administrated Cd per orally (PO) (15mg/Kg bw) alone or associated with an intraperitonial (IP) injection of alphatocopherol (Vitamin E) (300mg/Kg / day) for three weeks. We analyzed the effect of vitamin E on Cd induced liver remodeling by hematoxylin-eosin staining (HE), and by the determination of the antioxidant profiles and lipid peroxidation in rats's livers.RESULTS: Data confirmed that high dose of cd induced a loss of the liver weight and a pro-oxidative state into hepatocytes characterized by increased malondialdehyde (MDA) and peroxidase (POD), no changes in catalase (CAT) and a decrease on the superoxide dismutase (SOD) activities. These disturbances may be explained by a decrease in the level of hepatic calcium (Ca). Co-treatment with Vitamin E, decreased MDA and POD activities, increased CAT and SOD activities and restored Ca level. All these corrections were accompanied by an improvement of the liver 's structure.CONCLUSION: Our results suggest that Cd induced an oxidative stress into rat liver and Vitamin E exerted antioxidant properties which can be mediated by the modulation of Ca level.

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PMID: 

Nutr Neurosci. 2019 Oct 14:1-15. Epub 2019 Oct 14. PMID: 31607237

Abstract Title: 

Vitamin E attenuates alterations in learning, memory and BDNF levels caused by perinatal ethanol exposure.

Abstract: 

Alcohol exposure during pregnancy affects the developing fetus and causes a variety of physical and neurological abnormalities. Here we aim to study the effects of vitamin E on spatial learning and memory deficits and on changes in hippocampal brain-derived neurotrophic factor (BDNF) levels following perinatal ethanol exposure in rats.Pregnant Wistar rats received ethanol (4 g/kg) and vitamin E (doses of 100, 200, and 400 mg/kg) on day 0 of gestation (GD) until weaning (28 days). On postnatal days (PND) 29, the performance of spatial learning and memory of rats were measured using the Morris water maze (MWM). The expression of BDNF protein levels in the hippocampuswas assayed using BDNF ELISA kits.Ethanol exposed group showed higher escape latency during training, reduced time spent in the target quadrant, higher escape location latency and average proximity in probe test. Vitamin E with doses of 100, 200 and 400 mg/kg significantly reduced escape latency during training. Also, vitamin E (400 mg/kg) significantly increased time spent in target quadrant, decreased escape location latency and average proximity in probe test. Maternal ethanol treatment significantly reduced the expression of BDNF protein in the hippocampus of offspring, whereas administration of vitamin E (400 mg/kg) significantly increased hippocampal BDNF in ethanol-treated rats.Vitamin E administration dose-dependently ameliorate learning and memory deficits induced by perinatal ethanol exposure and increased hippocampal BDNF levels. BDNF may be implicated in the beneficial effects of vitamin E on learning and memory in the perinatal ethanol-exposed rat.

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PMID: 

J Nutr Sci Vitaminol (Tokyo). 2019 ;65(Supplement):S185-S187. PMID: 31619626

Abstract Title: 

Neuroprotective and Anti-Obesity Effects of Tocotrienols.

Abstract: 

Vitamin E is a natural lipophilic vitamin, and the most famous function of vitamin E is an antioxidant activity. Because we haveα-tocopherol transfer protein, many vitamin E-related reports are about α-tocopherol. Recently, other vitamin E isoforms, tocotrienols are focusing. Because tocotrienols have unique biological functions such as induction of apoptosis, neuroprotective and anti-obesity effects. Tocotrienols containin annatto, palm, whole wheat and rice bran. Rice is a typical food in the East Asian countries and Japan. Recently, intake of whole rice is a popular in young women of Japan. Previously, we demonstrated that treatment with tocotrienols on the neuronal cells shows a strong antioxidant effect compared to the tocopherols. In this review, I introduce about neuroprotective and anti-obesity effects of tocotrienols. I would like to show daily intake of whole rice is very good for our health in this review.

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PMID: 

Clin Exp Pharmacol Physiol. 2019 Oct 15. Epub 2019 Oct 15. PMID: 31612523

Abstract Title: 

Morphine stimulates angiogenesis through Akt/mTOR/eIF4E activation under serum deprivation or HO-induced oxidative stress condition.

Abstract: 

Morphine is an opioid analgesic drug routinely used to treat pain in several medical conditions including cancer. Increasing evidence has shown that morphine can directly modulate cancer growth via regulating angiogenesis. In this work, we investigated the effect of morphine on angiogenesis under pathological conditions. We showed that morphine, in a concentration typical of that observed in patient's blood, stimulates tumor angiogenesis under serum deprivation and HO-induced oxidative stress conditions. We found that morphine protected human lung tumor associated-endothelial cell (HLT-EC) against serum deprivation or HO-induced inhibition of capillary network formation. Furthermore, morphine stimulated other biological functions of HLT-EC under serum deprivation and HO-induced pathological conditions, such as growth, migration and survival, without affecting HLT-EC adhesion. Interestingly, morphine at the same concentration did not affect lung tumor cell growth and survival, suggesting the specific protective role of morphine at low micromolar concentrations on tumor angiogenesis. Using in vivo Matrigel angiogenesis assay, we found that morphine stimulated in vivo angiogenesis under HO-induced pathological condition. The opioid receptor antagonist, naloxone, did not inhibit the protective activity of morphine in in vivo angiogenesis, indicating that the effect was less likely to be mediated by the typical opioid receptors. Mechanism analysis indicated that morphine alleviated serum deprivation and HO-induced angiogenesis inhibition via reducing oxidative stress and damage, and activating Akt/mTOR/eIF4E signaling. We demonstrate the protective role of morphine on tumor angiogenesis under pathological conditions. Our work suggests that clinical use of morphine may be harmful in patients with angiogenesis-dependent cancers.

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PMID: 

Biochem Biophys Res Commun. 2019 Dec 10 ;520(3):560-565. Epub 2019 Oct 12. PMID: 31615652

Abstract Title: 

Morphine activates blast-phase chronic myeloid leukemia cells and alleviates the effects of tyrosine kinase inhibitors.

Abstract: 

Morphine is an opioid analgesic drug routinely used in the postoperative period for pain management in cancer patients. In this work, we analyzed the effects of morphine on leukemia cells at all stages of development and addressed its underlying mechanism. We showed that clinically relevant concentrations of morphine promoted growth without affecting survival in blast phase-chronic myeloid leukemia (BP-CML) K562 and LAMA84 cells. In addition, morphine alleviated the anti-proliferative and pro-apoptotic effects of BCR-ABL tyrosine kinase inhibitor (TKI) in BP-CML cells. We further found that morphine increased colony formation and replating capacity of CD34 stem/progenitor derived from BP-CML patients. In addition,morphine alleviated the inhibitory effects of BCR-ABL TKIs in cell survival, colony formation and replating capacity in BP-CML CD34  stem/progenitor cells. Mechanistic investigations demonstrated that morphine specifically activated Wnt signaling via increasing β-catenin activity and Wnt target genes transcription in K562 and CD34  stem/progenitor cells. The effects of morphine in BP-CML were abolished by Wnt inhibitor LGK-974 or XAV939, which further confirmed that morphine protected BP-CML cells from BCR-ABL TKIs-induced toxicity via activating Wnt/β-catenin signaling. Our work demonstrated the novel role of morphine onleukemia cells. The activation of Wnt/β-catenin by morphine may provide a new guide in the clinical use of morphine, particularly in patients with Wnt-driven cancers.

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PMID: 

Brain Behav Immun. 2019 Oct 15. Epub 2019 Oct 15. PMID: 31626971

Abstract Title: 

Morphine decreases the function of primary human natural killer cells by both TLR4 and opioid receptor signaling.

Abstract: 

BACKGROUND: Opioids are commonly used to provide analgesia for cancer pain, and functional opioid receptors have been identified on natural killer (NK) cells, the lymphocytes responsible for surveillance and elimination of cancer cells. Opioids also bind to other lymphocyte receptors, such as Toll-like receptor (TLR)-4. Here, we characterized the effects of morphine on primary human NK cell cytotoxicity and mediator release, which occur through classical opioid receptor or TLR4 signaling.METHODS: Purified primary human NK cells were pretreated with inhibitors of opioid receptors or TLR4 before being cultured with target tumor cell line K562 in the presence or absence of morphine. Apoptosis of K562 cells in each treatment condition was measured with an Annexin V flow cytometry-based assay and compared to that of K562 cells cultured with NK cells alone. Supernatant concentrations of 13 cytokines and cytotoxic mediators were measured with a multiplex bead-based flow cytometry assay.RESULTS: Exposure of NK cells to morphine decreased their ability to induce apoptosis in K562 cells. Pretreating the NK cells with either naloxone, a mu- and kappa-opioid receptor antagonist, or TAK-242, a selective inhibitor of TLR4 signaling, prevented this effect. Paradoxically, morphine increased the concentration of interleukin-6, granzyme A, and granzyme B in cell supernatants. Pretreatment of NK cells with TAK-242 prevented the morphine-induced increase in interleukin-6, whereas pretreatment with naloxone inhibited the morphine-induced increase in granzymes A and B.CONCLUSIONS: Both classical opioid receptors and TLR4 participate in morphine-induced suppression of NK cell cytotoxic activity. These studies have important implications for maintenance of immune function during management of cancer pain.

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PMID: 

J Alzheimers Dis. 2019 Oct 21. Epub 2019 Oct 21. PMID: 31658055

Abstract Title: 

Oral Monosodium Glutamate Administration Causes Early Onset of Alzheimer's Disease-Like Pathophysiology in APP/PS1 Mice.

Abstract: 

Glutamate excitotoxicity has long been related to Alzheimer's disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG,while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we observed a decrease in the AMPA receptor subunit GluA1 and they had impaired long-term potentiation. The Hebb-Williams maze revealed that they had memory deficits. We show here for the first time that oral MSG supplementation can accelerate AD-like pathophysiology in a mouse model of AD.

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PMID: 

Ultrastruct Pathol. 2019 Oct 28:1-14. Epub 2019 Oct 28. PMID: 31658851

Abstract Title: 

Testicular protective effects of ellagic acid on monosodium glutamate-induced testicular structural alterations in male rats.

Abstract: 

Ellagic acid (EA) has significant protective and antioxidant effects on several tissues. Monosodium glutamate (MG) is known as a flavor promoter that reversibly influences the male reproductive system. This study aims to assess the ameliorative effect of EA on oxidative stress and testicular damage induced by MG. In total, 48 male rats were included in this study and separated into six groups: control, EA (20 mg/kg), MG (low dose) (17.5 mg/kg), MG (high dose) (60 mg/kg), MG (low dose) combined with EA, and MG (high dose) combined with EA. Testicular antioxidant biomarkers [superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), catalase (CAT), myeloperoxidase (MPO), and xanthine oxidase (XO)] were examined. Testes were examined and scored for histological variation as an indicator of testicular damage following administration of MG alone or in combination with EA. Serum testosterone, inhibin B, 8-hydroxydeoxyguanosine (as a marker of DNA damage), and transmission electron microscope sections of the testis were evaluated, and a comet assay was performed. Results showed that administration of EA combined with MG significantly elevated the levels of enzymatic antioxidants and decreased lipid peroxidation compared with MG treatment alone. EA elevated testosterone hormone levels and thus enhanced male reproductive capacity. It is clear from the data that EA inhibits histological and ultrastructure testicular damage and improves the redox state in male rats.

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PMID: 

BMC Urol. 2019 Oct 28 ;19(1):103. Epub 2019 Oct 28. PMID: 31660941

Abstract Title: 

CoQ10 ameliorates monosodium glutamate-induced alteration in detrusor activity and responsiveness in rats via anti-inflammatory, anti-oxidant and channel inhibiting mechanisms.

Abstract: 

BACKGROUND: Competent detrusor muscles with coordinated contraction and relaxation are crucial for normal urinary bladder storage and emptying functions. Hence, detrusor instability, and subsequently bladder overactivity, may lead to undesirable outcomes including incontinence. Multiple mechanisms may underlie the pathogenesis of detrusor overactivity including inflammation and oxidative stress. Herein, we tested the possibility that CoQ10 may have a potential therapeutic role in detrusor overactivity.METHODS: Forty adult male Wistar albino rats weighing 100-150 g were used in the present study. Rats were divided (10/group) into control (receiving vehicles), monosodium glutamate (MSG)-treated (receiving 5 mg/kg MSG daily for 15 consecutive days), MSG + OO-treated (receiving concomitantly 5 mg/kg MSG and olive oil for 15 consecutive days), MSG + CoQ10-treated (receiving concomitantly 5 mg/kg MSG and 100 mg/kg CoQ10 daily for 15 consecutive days) groups.RESULTS: MSG resulted in significant increase in bladder weight and sensitised the bladder smooth muscles to acetylcholine. MSG has also resulted in significant increase in bladder TNF-α, IL-6, malondialdehyde, nerve growth factor and connexion 43, with significant decrease in the antioxidant enzymes superoxide dismutase and catalase. Olive oil had no effect on MSG induced alterations of different parameters. Treatment with CoQ10 has resulted in a significant restoration of all the altered parameters.CONCLUSION: Taken together, our results suggest that CoQ10 antagonizes the deleterious effects of MSG on detrusor activity. We propose that CoQ10 could be a therapeutic strategy targeting urinary bladder dysfunction.

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