Displaying publications 1 - 20 of 80 in total

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  1. Abd Jalil A, Khaza'ai H, Nordin N, Mansor N, Zaulkffali AS
    PMID: 29348770 DOI: 10.1155/2017/6048936
    Glutamate is the primary excitatory neurotransmitter in the central nervous system. Excessive concentrations of glutamate in the brain can be excitotoxic and cause oxidative stress, which is associated with Alzheimer's disease. In the present study, the effects of vitamin E in the form of tocotrienol-rich fraction (TRF) and alpha-tocopherol (α-TCP) in modulating the glutamate receptor and neuron injury markers in an in vitro model of oxidative stress in neural-derived embryonic stem (ES) cell cultures were elucidated. A transgenic mouse ES cell line (46C) was differentiated into a neural lineage in vitro via induction with retinoic acid. These cells were then subjected to oxidative stress with a significantly high concentration of glutamate. Measurement of reactive oxygen species (ROS) was performed after inducing glutamate excitotoxicity, and recovery from this toxicity in response to vitamin E was determined. The gene expression levels of glutamate receptors and neuron-specific enolase were elucidated using real-time PCR. The results reveal that neural cells derived from 46C cells and subjected to oxidative stress exhibit downregulation of NMDA, kainate receptor, and NSE after posttreatment with different concentrations of TRF and α-TCP, a sign of neurorecovery. Treatment of either TRF or α-TCP reduced the levels of ROS in neural cells subjected to glutamate-induced oxidative stress; these results indicated that vitamin E is a potent antioxidant.
    Matched MeSH terms: Glutamic Acid
  2. Sani MH, Taher M, Susanti D, Kek TL, Salleh MZ, Zakaria ZA
    Biol Res Nurs, 2015 Jan;17(1):68-77.
    PMID: 25504952 DOI: 10.1177/1099800414529648
    Elucidate the antinociceptive mechanisms of α-mangostin isolated from Garcinia malaccensis Linn.
    Matched MeSH terms: Glutamic Acid/administration & dosage
  3. Aljuboori AH, Uemura Y, Osman NB, Yusup S
    Bioresour Technol, 2014 Nov;171:66-70.
    PMID: 25189510 DOI: 10.1016/j.biortech.2014.08.038
    This study evaluated the potential of bioflocculant production from Aspergillus niger using palm oil mill effluent (POME) as carbon source. The bioflocculant named PM-5 produced by A. niger showed a good flocculating capability and flocculating rate of 76.8% to kaolin suspension could be achieved at 60 h of culture time. Glutamic acid was the most favorable nitrogen source for A. niger in bioflocculant production at pH 6 and temperature 35 °C. The chemical composition of purified PM-5 was mainly carbohydrate and protein with 66.8% and 31.4%, respectively. Results showed the novel bioflocculant (PM-5) had high potential to treat river water from colloids and 63% of turbidity removal with the present of Ca(2+) ion.
    Matched MeSH terms: Glutamic Acid/metabolism
  4. Wan Nasru WN, Ab Razak A, Yaacob NM, Wan Azman WN
    Malays J Pathol, 2021 Apr;43(1):25-32.
    PMID: 33903302
    INTRODUCTION: The amino acids that function as co-agonists at the N-methyl-D-aspartate (NMDA) receptor have been investigated in bipolar disorder (BD). However, studies comparing amino acid levels in the plasma of BD patients with healthy controls have yielded inconsistent results. We, therefore, conducted a study in Hospital Universiti Sains Malaysia to determine the plasma levels of glutamate, glycine, and alanine in BD patients and compared them with the healthy controls.

    MATERIALS AND METHODS: An overnight fast of 10-hour plasma levels of glutamate, glycine, alanine, and tryptophan were measured in 83 bipolar patients, and were compared to a group of 82 healthy controls.

    RESULTS: The mean (SD) age of bipolar patients was 40.9 (12.1), while the mean (SD) age for control groups was 35.6 (7.7) years. The median (25th, 75th percentile) of glutamate and alanine levels in bipolar patients was 111.0 (65.0,176.0) and 530.0 (446.0,629.0), respectively, while the mean (SD) of glycine level in bipolar patients was 304.0 (98.1). Significant higher glutamate, glycine, and alanine levels were found in bipolar disorder patients in the manic episode as compared to the healthy controls.

    CONCLUSION: Although the exact relationship between peripheral NMDA receptor co-agonist levels in the pathogenesis of BD is not well understood, these findings should be explored and may enlighten some new paths for BD therapy which could reward the patients also clinicians.

    Matched MeSH terms: Glutamic Acid
  5. Selvaraju TR, Khaza'ai H, Vidyadaran S, Abd Mutalib MS, Vasudevan R
    Bosn J Basic Med Sci, 2014 Nov 16;14(4):195-204.
    PMID: 25428670 DOI: 10.17305/bjbms.2014.4.91
    Tocotrienol rich fraction (TRF) is an extract of palm oil, which consists of 25% alpha tocopherol (α-TCP) and 75% tocotrienols. TRF has been shown to possess potent antioxidant, anti-inflammatory, anticancer, neuroprotection, and cholesterol lowering activities. Glutamate is the main excitatory amino acid neurotransmitter in the central nervous system of mammalian, which can be excitotoxic, and it has been suggested to play a key role in neurodegenerative disorders like Parkinson's and Alzheimer's diseases. In this present study, the effects of vitamin E (TRF and α-TCP) in protecting astrocytes against glutamate injury were elucidated. Astrocytes induced with 180 mM of glutamate lead to significant cell death. However, glutamate mediated cytotoxicity was diminished via pre and post supplementation of TRF and α-TCP. Hence, vitamin E acted as a potent antioxidant agent in recovering mitochondrial injury due to elevated oxidative stress, and enhanced better survivability upon glutamate toxicity.
    Matched MeSH terms: Glutamic Acid/toxicity*
  6. Fukumoto J, Ismail NI, Kubo M, Kinoshita K, Inoue M, Yuasa K, et al.
    J. Biochem., 2013 Nov;154(5):465-73.
    PMID: 23946505 DOI: 10.1093/jb/mvt077
    Oligopeptidase B (OPB) is a member of the prolyl oligopeptidase (POP) family of serine proteases. OPB in trypanosomes is an important virulence factor and potential pharmaceutical target. Characteristic structural features of POP family members include lack of a propeptide and presence of a β-propeller domain (PD), although the role of the β-PD has yet to be fully understood. In this work, residues Glu(172), Glu(490), Glu(524) and Arg(689) in Trypanosoma brucei OPB (Tb OPB), which are predicted to form inter-domain salt bridges, were substituted for Gln and Ala, respectively. These mutants were evaluated in terms of catalytic properties and stability. A negative effect on kcat/Km was obtained following mutation of Glu(172) or Arg(689). In contrast, the E490Q mutant exhibited markedly decreased thermal stability, although this mutation had less effect on catalytic properties compared to the E172Q and R689A mutants. Trypsin digestion showed that the boundary regions between the β-PD and catalytic domains (CDs) of the E490Q mutant are unfolded with heat treatment. These results indicated that Glu(490) in the CD plays a role in stabilization of Tb OPB, whereas Glu(172) in the β-PD is critical for the catalytic activity of Tb OPB.
    Matched MeSH terms: Glutamic Acid/genetics; Glutamic Acid/metabolism*
  7. Chia, Yoke Yin, Ton, So Ha
    Malays J Nutr, 2006;12(1):67-78.
    MyJurnal
    The objective of the study was to quantify and to profile the amino acids content in urine samples. The amino acids content in urine was determined in 162 individuals (62 young non-vegetarians aged 15-45 years, 24 elderly non-vegetarians aged 46-70 years, 40 young vegetarians and 36 elderly vegetarians) by high performance liquid chromatography (HPLC). The most common amino acids detected in the young and elderly individuals on vegetarian and non-vegetarian diets were phenylalanine, threonine, arginine and asparagine, while leucine, aspartic acid and alanine were not found in any urine samples in both groups. Isoleucine was not detected in the urine of vegetarians. The concentrations of the majority of essential amino acids were between 0.10 - 2.00 mgl24hrs except for histidine which had a range of 4.1 - 5.0 mgl24hrs. The concentrations of non-essential amino acids varied. Proline, glycine and tyrosine concentrations were between 0.10 - 1.00 mg/24hrs, while cysteine, glutamine, glutamic acid and cystine concentrations were between 11.0 - 21.0 mg124hrs. Asparagine and hydroxy-proline had a range of 0.10 - 5.00 mg/24hrs, while serine and arginine ranged between 31.0 - 50.0 mg124hrs. Isoleucine and serine were not detected in elderly vegetarians while histidine, glycine, glutamic acid and hydroxy-proline were not detected in elderly non-vegetarians. Isoleucine, glycine and hydroxy proline were detected in young non-vegetarians but not in young vegetarians. The levels of amino acids showed no significant statistical differences between young vegetarians and non-vegetarians as well as between elderly vegetarians and non-vegetarians. Phenylalanine, threonine and trypthophan were commonly detected in the lacto-ovo and lacto vegetarians, while valine, cysteine, arginine and asparagine were commonly detected in vegans. In conclusion, except for isoleucine, general differences were seen in urinary amino acid excretions between vegetarians and non-vegetarians even though the differences were statistically not significant. Therefore lacto-ovo diets could be nutritionally adequate as the nutrients were substituted by dairy or plant products.
    Matched MeSH terms: Glutamic Acid
  8. Nor Faadila, M.I., Harivaindaran, K.V., Tajul, A. Yang
    MyJurnal
    Texture and biochemical changes, specifically in moisture, protein content and amino acid profile were studied throughout the molt cycle of Panaeus monodon. This study was initiated to investigate changes that may occur in mass and tissue composition during different molting stages. Molting of Penaeus monodon are classified into 3 main stages; postmolt, intermolt and premolt. Result of biochemical analysis, shows that moisture varies from 78.02-80.88%, indicating a maximum value during postmolt and minimum value during premolt. Total protein content was found to be higher during intermolt (23.48%) and postmolt (22.27%) compared to premolt (23.10%). The result of SDS-PAGE electrophoresis shows a higher intensity of protein band during intermolt which corresponds to higher protein content. Thus, this electrophoresis method is useful as an alternative to determine different stages of shrimp molting. This is based on intensity of the protein band which is referring to protein content of the shrimp at its different stages. The amino acid profile showed that arginine, alanine, glutamic acid, glycine, lycine, and thronine increased during premolt whilst isoleucine and phenylalanine higher during postmolt. Aspartic acid and histidine was higher in intermolt than in premolt and postmolt. Texture analysis carried out give an elastic modulus value that is high during premolt compared to postmolt and intermolt. There are significant changes in texture and biochemical composition through elastic modules value and protein composition of Penaeus monodon during each stages of moltcycle.
    Matched MeSH terms: Glutamic Acid
  9. Ng S, Lasekan O, Muhammad KS, Hussain N, Sulaiman R
    J Food Sci Technol, 2015 Oct;52(10):6623-30.
    PMID: 26396409 DOI: 10.1007/s13197-015-1737-z
    The seeds of Terminalia catappa from Malaysia were analyzed for their physicochemical properties. The following values were obtained: moisture 6.23 ± 0.09 %, ash 3.78 ± 0.04 %, lipid 54.68 ± 0.14 %, protein 17.66 ± 0.13 %, total dietary fibre 9.97 ± 0.08 %, carbohydrate 7.68 ± 0.06 %, reducing sugar 1.36 ± 0.16 %, starch 1.22 ± 0.15 %, caloric value 593.48 ± 0.24 %. Studies were also conducted on amino acid profile and free fatty acid composition of the seed oil. Results revealed that glutamic acid was the major essential amino acid while methionine and lysine were the limiting amino acids. The major saturated fatty acid was palmitic acid, while the main unsaturated fatty acid was oleic acid followed by linoleic acid. In addition, the seed was rich in sucrose and had trace amount of glucose and fructose. Briefly, the seed was high in proteins and lipids which are beneficial to human.
    Matched MeSH terms: Glutamic Acid
  10. Mohamad AS, Akhtar MN, Zakaria ZA, Perimal EK, Khalid S, Mohd PA, et al.
    Eur J Pharmacol, 2010 Nov 25;647(1-3):103-9.
    PMID: 20826146 DOI: 10.1016/j.ejphar.2010.08.030
    The present study examined the potential antinociceptive activity of flavokawin B (6'-hydroxy-2',4'-dimethoxychalcone), a synthetic chalcone using chemical- and thermal-induced nociception models in mice. It was demonstrated that flavokawin B (FKB; 0.3, 1, 3 and 10 mg/kg) administered via both oral (p.o.) and intraperitoneal (i.p.) routes produced significant and dose-dependent inhibition in the abdominal constrictions induced by acetic acid, with the i.p. route producing antinociception of approximately 7-fold more potent than the p.o. route. It was also demonstrated that FKB produced significant inhibition in the two phases of the formalin-induced paw licking test. In addition, the same treatment of flavokawin B (FKB) exhibited significant inhibition of the neurogenic nociceptive induced by intraplantar injections of glutamate and capsaicin. Likewise, this compound also induced a significant increase in the response latency period to thermal stimuli in the hot plate test and its antinociceptive effect was not related to muscle relaxant or sedative action. Moreover, the antinociception effect of the FKB in the formalin-induced paw licking test and the hot plate test was not affected by pretreatment of non-selective opioid receptor antagonist, naloxone. The present results indicate that FKB produced pronounced antinociception effect against both chemical and thermal models of pain in mice that exhibited both peripheral and central analgesic activity.
    Matched MeSH terms: Glutamic Acid/metabolism
  11. Pui Ping C, Akhtar MN, Israf DA, Perimal EK, Sulaiman MR
    Molecules, 2020 Nov 18;25(22).
    PMID: 33217904 DOI: 10.3390/molecules25225385
    The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg/kg (0.9-4.5 mg/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine/nitric oxide/cGMP pathway and ATP-sensitive K+ channel.
    Matched MeSH terms: Glutamic Acid
  12. Ping CP, Tengku Mohamad TAS, Akhtar MN, Perimal EK, Akira A, Israf Ali DA, et al.
    Molecules, 2018 Sep 03;23(9).
    PMID: 30177603 DOI: 10.3390/molecules23092237
    Pain is one of the most common cause for hospital visits. It plays an important role in inflammation and serves as a warning sign to avoid further injury. Analgesics are used to manage pain and provide comfort to patients. However, prolonged usage of pain treatments like opioids and NSAIDs are accompanied with undesirable side effects. Therefore, research to identify novel compounds that produce analgesia with lesser side effects are necessary. The present study investigated the antinociceptive potentials of a natural compound, cardamonin, isolated from Boesenbergia rotunda (L) Mansf. using chemical and thermal models of nociception. Our findings showed that intraperitoneal and oral administration of cardamonin (0.3, 1, 3, and 10 mg/kg) produced significant and dose-dependent inhibition of pain in abdominal writhing responses induced by acetic acid. The present study also demonstrated that cardamonin produced significant analgesia in formalin-, capsaicin-, and glutamate-induced paw licking tests. In the thermal-induced nociception model, cardamonin exhibited significant increase in response latency time of animals subjected to hot-plate thermal stimuli. The rota-rod assessment confirmed that the antinociceptive activities elicited by cardamonin was not related to muscle relaxant or sedative effects of the compound. In conclusion, the present findings showed that cardamonin exerted significant peripheral and central antinociception through chemical- and thermal-induced nociception in mice through the involvement of TRPV₁, glutamate, and opioid receptors.
    Matched MeSH terms: Glutamic Acid/metabolism*
  13. Khalid MH, Akhtar MN, Mohamad AS, Perimal EK, Akira A, Israf DA, et al.
    J Ethnopharmacol, 2011 Sep 01;137(1):345-51.
    PMID: 21664960 DOI: 10.1016/j.jep.2011.05.043
    ETHNOPHARMACOLOGICAL RELEVANCE: Zingiber zerumbet (L.) Smith, a wild edible ginger species or locally known as "lempoyang", commonly used in the Malays traditional medicine as an appetizer or to treat stomachache, toothache, muscle sprain and as a cure for swelling sores and cuts.

    AIM: The present study was conducted to investigate the possible mechanism of actions underlying the systemic antinociception activity of the essential oil of Zingiber zerumbet (EOZZ) in chemical-induced nociception tests in mice.

    MATERIALS AND METHODS: Acetic acid-induced abdominal constriction, capsaicin-, glutamate- and phorbol 12-myristate 13-acetate-induced paw licking tests in mice were employed in the study. In all experiments, EOZZ was administered systemically at the doses of 50, 100, 200 and 300 mg/kg.

    RESULTS: It was shown that EOZZ given to mice via intraperitoneal and oral routes at 50, 100, 200 and 300 mg/kg produced significant dose dependent antinociception when assessed using acetic acid-induced abdominal writing test with calculated mean ID(50) values of 88.84 mg/kg (80.88-97.57 mg/kg) and 118.8 mg/kg (102.5-137.8 mg/kg), respectively. Likewise, intraperitoneal administration of EOZZ at similar doses produced significant dose dependent inhibition of neurogenic pain induced by intraplantar injection of capsaicin (1.6 μg/paw), glutamate (10 μmol/paw) and phorbol 12-myristate 13-acetate (1.6μg/paw) with calculated mean ID(50) of 128.8 mg/kg (118.6-139.9 mg/kg), 124.8 mg/kg (111.4-139.7 mg/kg) and 40.29 (35.39-45.86) mg/kg, respectively. It was also demonstrated that pretreatment with l-arginine (100mg/kg, i.p.), a nitric oxide precursor significantly reversed antinociception produced by EOZZ suggesting the involvement of l-arginine/nitric oxide pathway. In addition, methylene blue (20mg/kg, i.p.) significantly enhanced antinociception produced by EOZZ. Administration of glibenclamide (10mg/kg, i.p.), an ATP-sensitive K(+) channel antagonist significantly reversed antinociceptive activity induced by EOZZ.

    CONCLUSION: Together, the present results suggested that EOZZ-induced antinociceptive activity was possibly related to its ability to inhibit glutamatergic system, TRPV1 receptors as well as through activation of l-arginine/nitric oxide/cGMP/protein kinase C/ATP-sensitive K(+) channel pathway.

    Matched MeSH terms: Glutamic Acid/metabolism
  14. Ismail NI, Ming-Tatt L, Lajis N, Akhtar MN, Akira A, Perimal EK, et al.
    Molecules, 2016 Aug 22;21(8).
    PMID: 27556438 DOI: 10.3390/molecules21081077
    The antinociceptive effects produced by intraperitoneal administration of a novel synthetic chalcone, 3-(2,3-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMFP), were investigated in several mouse models of induced nociception. The administration of DMFP (0.1, 0.5, 1.0 and 5.0 mg/kg) produced significant attenuation on the acetic acid-induced abdominal-writhing test. It also produced a significant increase in response latency time in the hot-plate test and a marked reduction in time spent licking the injected paw in both phases of the formalin-induced paw-licking test. In addition, it was also demonstrated that DMFP exhibited significant inhibition of the neurogenic nociceptive response induced by intraplantar injections of capsaicin and glutamate. Moreover, the antinociceptive effect of DMFP in the acetic acid-induced abdominal-writhing test and the hot-plate test was not antagonized by pretreatment with a non-selective opioid receptor antagonist, naloxone. Finally, DMFP did not show any toxic effects and/or mortality in a study of acute toxicity and did not interfere with motor coordination during the Rota-rod test. Our present results show that DMFP exhibits both peripheral and central antinociceptive effects. It was suggested that its peripheral antinociceptive activity is associated with attenuated production and/or release of NO and various pro-inflammatory mediators, while central antinociceptive activity seems to be unrelated to the opioidergic system, but could involve, at least in part, an interaction with the inhibition of capsaicin-sensitive fibers and the glutamatergic system.
    Matched MeSH terms: Glutamic Acid/adverse effects*
  15. Zulkifli I, Shakeri M, Soleimani AF
    Poult Sci, 2016 Sep 1.
    PMID: 27587729
    This study was conducted to investigate the effect of dietary glutamine (Gln) + glutamic acid (Glu) supplementation on growth performance and physiological stress response in broiler chickens subjected to 24 h delay in placement. Equal number of day-old broiler chicks were assigned to either immediate placement or with 24 h delay in placement with no access to feed and water. Chicks from each placement group were fed either standard starter diet (control) or standard starter diet +1% AminoGut (AG; mixture of 10% Gln and 10% Glu) from 1 to 21 d. Blood and duodenal samples were collected at 21 d for analysis of serum levels of ceruloplasmin (CER), ovotransferin (OVT) and α-1 acid glycoprotein (AGP), duodenal heat shock protein (HSP) 70 expression, and villi length and crypt depth. Results showed that delayed placement for 24 h was detrimental to weight gain during the starter phase (1 to 21 d) but not thereafter. AG supplementation was not able to eliminate that reduction in weight gain and feed intake during the starter stage. However, the observed enhancement in villi length and crypt depth at d 21 resulted in improvement of FCR and weight gain during the finisher stage (22 to 42 d) and consequently the overall period (1 to 42 d). Broiler chickens supplemented with AG also showed lower mortality rate, and higher AGP, OVT, CER, and HSP 70 expression compared to their control counterparts. Based on AGP, OVT, CER, and HSP 70 expression, there is no indication that delayed placement was physiologically stressful to the broiler chickens at 21 d of age.
    Matched MeSH terms: Glutamic Acid
  16. Paudel YN, Othman I, Shaikh MF
    Front Pharmacol, 2020;11:613009.
    PMID: 33732146 DOI: 10.3389/fphar.2020.613009
    Epilepsy is a chronic brain disease afflicting around 70 million global population and is characterized by persisting predisposition to generate epileptic seizures. The precise understanding of the etiopathology of seizure generation is still elusive, however, brain inflammation is considered as a major contributor to epileptogenesis. HMGB1 protein being an initiator and crucial contributor of inflammation is known to contribute significantly to seizure generation via activating its principal receptors namely RAGE and TLR4 reflecting a potential therapeutic target. Herein, we evaluated an anti-seizure and memory ameliorating potential of an anti-HMGB1 monoclonal antibody (mAb) (1, 2.5 and 5 mg/kg, I.P.) in a second hit Pentylenetetrazol (PTZ) (80 mg/kg, I.P.) induced seizure model earlier stimulated with Pilocarpine (400 mg/kg, I.P.) in adult zebrafish. Pre-treatment with anti-HMGB1 mAb dose-dependently lowered the second hit PTZ-induced seizure but does not alter the disease progression. Moreover, anti-HMGB1 mAb also attenuated the second hit Pentylenetetrazol induced memory impairment in adult zebrafish as evidenced by an increased inflection ration at 3 and 24 h trail in T-maze test. Besides, decreased level of GABA and an upregulated Glutamate level was observed in the second hit PTZ induced group, which was modulated by pre-treatment with anti-HMGB1 mAb. Inflammatory responses occurred during the progression of seizures as evidenced by upregulated mRNA expression of HMGB1, TLR4, NF-κB, and TNF-α, in a second hit PTZ group, which was in-turn downregulated upon pre-treatment with anti-HMGB1 mAb reflecting its anti-inflammatory potential. Anti-HMGB1 mAb modulates second hit PTZ induced changes in mRNA expression of CREB-1 and NPY. Our findings indicates anti-HMGB1 mAb attenuates second hit PTZ-induced seizures, ameliorates related memory impairment, and downregulates the seizure induced upregulation of inflammatory markers to possibly protect the zebrafish from the incidence of further seizures through via modulation of neuroinflammatory pathway.
    Matched MeSH terms: Glutamic Acid
  17. Kundap UP, Paudel YN, Kumari Y, Othman I, Shaikh MF
    Front Pharmacol, 2019;10:315.
    PMID: 31057394 DOI: 10.3389/fphar.2019.00315
    Epilepsy is a neuronal disorder associated with several neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Despite having more than 20 anti-epileptic drugs (AEDs), they only provide a symptomatic treatment. As well as, currently available AEDs also displayed cognitive alterations in addition to retarding seizure. This leads to the need for exploring new molecules that not only retard seizure but also improve cognitive impairment. Embelin (EMB) is a benzoquinone derivative which has already demonstrated its pharmacological potentials against arrays of neurological conditions. The current study developed a chronic kindling model in adult zebrafish by using repeated administration of small doses of pentylenetetrazole (PTZ) and a single dose of Kainic acid (KA) to investigate the associated memory impairment. This has been done by using the three-axis maze which is a conventional method to test the learning ability and egocentric memory in zebrafish. As well as, the ameliorative potential of EMB has been evaluated against chronic epilepsy-related memory alterations. Moreover the expression level of pro-inflammatory genes such as C-C motif ligand 2 (CCL2), toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interferon-γ (IFN-γ) were evaluated. The level of several neurotransmitters such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamate (Glu) was evaluated by liquid chromatography-mass spectrometry (LC-MS). The results showed that daily dose of PTZ 80 mg/kg for 10 days successfully induces a kindling effect in zebrafish, whereas the single dose of KA did not. As compared to control, the PTZ and KA group demonstrates impairment in memory as demonstrated by the three-axis maze. The PTZ group treated with a series of EMB doses (ranging from 0.156 to 0.625 mg/kg) was found to have retarded seizure as well as significantly reduces epilepsy-induced memory alteration. In addition, EMB treatment reduces the expression of inflammatory markers implicating its anti-inflammatory potential. Moreover, levels of GABA, Ach, and glutamate are increased in EMB administered group as compared to the PTZ administered group. Overall, findings demonstrate that EMB might be a potential candidate against chronic epilepsy-related cognitive dysfunction as EMB prevents the seizures, so we expect it to prevent the associated neuroinflammation and learning deficit.
    Matched MeSH terms: Glutamic Acid
  18. Choo BKM, Kundap UP, Johan Arief MFB, Kumari Y, Yap JL, Wong CP, et al.
    PMID: 30844417 DOI: 10.1016/j.pnpbp.2019.02.014
    Epilepsy is marked by seizures that are a manifestation of excessive brain activity and is symptomatically treatable by anti-epileptic drugs (AEDs). Unfortunately, the older AEDs have many side effects, with cognitive impairment being a major side effect that affects the daily lives of people with epilepsy. Thus, this study aimed to determine if newer AEDs (Zonisamide, Levetiracetam, Perampanel, Lamotrigine and Valproic Acid) also cause cognitive impairment, using a zebrafish model. Acute seizures were induced in zebrafish using pentylenetetrazol (PTZ) and cognitive function was assessed using the T-maze test of learning and memory. Neurotransmitter and gene expression levels related to epilepsy as well as learning and memory were also studied to provide a better understanding of the underlying processes. Ultimately, impaired cognitive function was seen in AED treated zebrafish, regardless of whether seizures were induced. A highly significant decrease in γ-Aminobutyric Acid (GABA) and glutamate levels was also discovered, although acetylcholine levels were more variable. The gene expression levels of Brain-Derived Neurotrophic Factor (BDNF), Neuropeptide Y (NPY) and Cyclic Adenosine Monophosphate (CAMP) Responsive Element Binding Protein 1 (CREB-1) were not found to be significantly different in AED treated zebrafish. Based on the experimental results, a decrease in brain glutamate levels due to AED treatment appears to be at least one of the major factors behind the observed cognitive impairment in the treated zebrafish.
    Matched MeSH terms: Glutamic Acid/metabolism
  19. Chung YS, Choo BKM, Ahmed PK, Othman I, Shaikh MF
    Biomedicines, 2020 Jul 02;8(7).
    PMID: 32630817 DOI: 10.3390/biomedicines8070191
    The anticonvulsive potential of proteins extracted from Orthosiphon stamineus leaves (OSLP) has never been elucidated in zebrafish (Danio rerio). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure onset time, behavior, locomotor) and neurotransmitter analysis were elucidated to assess the pharmacological activity. The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification (LFQ) and bioinformatics. OSLP was found to be safe up to 800 µg/kg and pre-treatment with OSLP (800 µg/kg, i.p., 30 min) decreased the frequency of convulsive activities (lower seizure score and prolonged seizure onset time), improved locomotor behaviors (reduced erratic swimming movements and bottom-dwelling habit), and lowered the excitatory neurotransmitter (glutamate). Pre-treatment with OSLP increased protein Complexin 2 (Cplx 2) expression in the zebrafish brain. Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis. Findings in this study collectively suggests that OSLP could be regulating the release of neurotransmitters via calcium-dependent synaptic vesicle exocytosis mediated by the "Synaptic Vesicle Cycle" pathway. OSLP's anticonvulsive actions could be acting differently from diazepam (DZP) and with that, it might not produce the similar cognitive insults such as DZP.
    Matched MeSH terms: Glutamic Acid
  20. Kundap UP, Kumari Y, Othman I, Shaikh MF
    Front Pharmacol, 2017;8:515.
    PMID: 28824436 DOI: 10.3389/fphar.2017.00515
    Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. Anti-epileptic drugs (AEDs) are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs.
    Matched MeSH terms: Glutamic Acid
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