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Fulltext Age-related changes in the metabolic profiles of rat hippocampus, medial prefrontal cortex and striatum

Durani LW, Hamezah HS, Ibrahim NF, Yanagisawa D, Makpol S, Damanhuri HA, et al.

Biochem Biophys Res Commun, 2017 11 25;493(3):1356-1363.
PMID: 28970069 DOI: 10.1016/j.bbrc.2017.09.164

We have recently shown that age-dependent regional brain atrophy and lateral ventricle expansion may be linked with impaired cognitive and locomotor functions. However, metabolic profile transformation in different brain regions during aging is unknown. This study examined metabolic changes in the hippocampus, medial prefrontal cortex (mPFC) and striatum of middle- and late-aged Sprague-Dawley rats using ultrahigh performance liquid chromatography coupled with high-resolution accurate mass-orbitrap tandem mass spectrometry. Thirty-eight potential metabolites were altered in hippocampus, 29 in mPFC, and 14 in striatum. These alterations indicated that regional metabolic mechanisms in lated-aged rats are related to multiple pathways including glutathione, sphingolipid, tyrosine, and purine metabolism. Thus, our findings might be useful for understanding the complexity of metabolic mechanisms in aging and provide insight for aging and health span.

Matched MeSH terms: Glutathione/metabolism
Characteristics of Pelargonium radula as a mercury bioindicator for safety assessment of drinking water

Majid NA, Phang IC, Darnis DS

Environ Sci Pollut Res Int, 2017 Oct;24(29):22827-22838.
PMID: 28150147 DOI: 10.1007/s11356-017-8484-9

Identification of Pelargonium radula as bioindicator for mercury (Hg) detection confers a new hope for monitoring the safety of drinking water consumption. Hg, like other non-essential metals, inflicts the deterioration of biological functions in human and other creatures. In the present study, effects of Hg on the physiology and biochemical content of P. radula were undertaken to understand the occurrence of the morphological changes observed. Young leaves of P. radula were treated with different concentrations of Hg-containing solution (0.5, 1.0 and 2.0 ppb) along with controls for 4 h, prior to further analysis. Elevated Hg concentration in treatment solution significantly prompted an increased accumulation of Hg in the leaf tissues. Meanwhile, total protein, chlorophyll and low molecular mass thiol contents (cysteine, glutathione and oxidized glutathione) decreased as Hg accumulation increased. However, phytochelatin 2 productions were induced in the treated leaves, in comparison to the control. Based on these findings, it is postulated that as low as 0.5 ppb of Hg interferes with the metabolic processes of plant cells, which was reflected from the morphological changes exhibited on P. radula leaves-the colour of the Hg-treated leaves changed from green to yellowish-brown, became chlorosis and wilted. Changes in the tested characteristics of plant are closely related to the Hg-induced morphological changes on P. radula leaves, a potential bioindicator for detecting Hg in drinking water.

Matched MeSH terms: Glutathione/metabolism
Reactive oxygen species and glutathione antioxidants in the testis of the soil biosentinel Podarcis sicula (Rafinesque 1810)

Guerriero G, D'Errico G, Di Giaimo R, Rabbito D, Olanrewaju OS, Ciarcia G

Environ Sci Pollut Res Int, 2018 Jul;25(19):18286-18296.
PMID: 28936697 DOI: 10.1007/s11356-017-0098-8

Important toxicological achievements have been made during the last decades using reptiles. We focus our investigation on gonadal reproductive health of the soil biosentinel Podarcis sicula which is very sensitive to endocrine-disrupting chemicals. The aim of this study is to quantitatively detect, by sensitive microassays, reactive oxygen species and the glutathione antioxidants in the testis and investigate if they are differentially expressed before and after remediation of a site of the "Land of Fires" (Campania, Italy) subject to illicit dumping of unknown material. The oxidative stress level was evaluated by electron spin resonance spectroscopy applying a spin-trapping procedure able to detect products of lipid peroxidation, DNA damage and repair by relative mobility shift, and poly(ADP-ribose) polymerase enzymatic activity, respectively, the expression of glutathione peroxidase 4 transcript by real-time quantitative PCR analysis, the antioxidant glutathione S-transferase, a well-assessed pollution index, by enzymatic assay and the total soluble antioxidant capacity. Experimental evidences from the different techniques qualitatively agree, thus confirming the robustness of the combined experimental approach. Collected data, compared to those from a reference unpolluted site constitute evidence that the reproductive health of this lizard is impacted by pollution exposure. Remediation caused significant reduction of reactive oxygen species and downregulation of glutathione peroxidase 4 mRNAs in correspondence of reduced levels of glutathione S-transferase, increase of antioxidant capacity, and repair of DNA integrity. Taken together, our results indicate directions to define new screening approaches in remediation assessment.

Matched MeSH terms: Glutathione/metabolism*
Tocotrienol rich fraction prevents fenitrothion induced pancreatic damage by restoring antioxidant status

Budin SB, Han CM, Jayusman PA, Taib IS

Pak J Biol Sci, 2012 Jun 01;15(11):517-23.
PMID: 24191625

Fenitrothion (FNT) is extensively used as pesticide and may induce oxidative stress in various organs. Tocotrienol, a form of vitamin E found in palm oil, reduces oxidative impairments in pathological conditions. This study aims to investigate the effects of palm oil tocotrienol rich fraction (TRF) on fenitrothion-induced oxidative damage in rat pancreas. Forty male Sprague-Dawley rats were divided into four groups: control group, FNT group, TRF group and FNT+TRF group. Regimens FNT (20 mg kg(-1) b.wt.) and TRF (200 mg kg(-1) b.wt.) were force-fed for 28 consecutive days with control group only receiving corn oil. Chronic administration of fenitrothion significantly (p < 0.05) induced oxidative damage in pancreas of rats with elevated malondialdehyde and protein carbonyl level. Depletion of glutathione and significant (p < 0.05) reduction in antioxidant enzyme activities in pancreas homogenate additionally suggested induction of oxidative stress. Despite these changes in pancreas of intoxicated rats, no significant (p < 0.05) changes in blood glucose and pancreas histology were observed. Co-administration of FNT with TRF alleviated these oxidative changes and significantly (p < 0.05) restored antioxidant status. Enzymatic activities of Superoxide Dismutase (SOD) and Catalase (CAT) were normalized. In conclusion, tocotrienol rich fraction of palm oil prevents fenitrothion-induced pancreatic oxidative damage in rats.

Matched MeSH terms: Glutathione/metabolism
Neuroprotective properties of Loranthus parasiticus aqueous fraction against oxidative stress-induced damage in NG108-15 cells

Wong DZ, Kadir HA, Lee CL, Goh BH

J Nat Med, 2012 Jul;66(3):544-51.
PMID: 22318341 DOI: 10.1007/s11418-011-0622-y

Loranthus parasiticus, a Chinese folk medicine, has been widely used for the treatment of brain diseases, particularly in southwest China. Hence, the present neuroprotection model was designed to investigate its neuroprotective properties against H(2)O(2)-induced oxidative stress in NG108-15 cells. L. parasiticus aqueous fraction (LPAF), which was selected in the present study, had proved to be the most active fraction among the other tested extracts and fractions in our previous screening. The restoration of depleted intracellular glutathione (GSH), a major endogenous antioxidant, by LPAF was observed after H(2)O(2) insult. Pretreatment with LPAF substantially reduced the production of intracellular reactive oxygen species generated from H(2)O(2). Apoptotic features such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential were significantly attenuated by LPAF. In addition, cell cycle analysis revealed a prominent decrease in the H(2)O(2)-induced sub-G(1) population by LPAF. Moreover, apoptotic morphological analysis by DAPI nuclear staining demonstrated that NG108-15 cells treated with H(2)O(2) exhibited apoptotic features, while such changes were greatly reduced in cells pretreated with LPAF. Taken together, these findings confirmed that LPAF exerts marked neuroprotective activity, which raises the possibility of potential therapeutic application of LPAF for managing oxidative stress-related neurological disorders and supports the traditional use of L. parasiticus in treating brain-related diseases.

Matched MeSH terms: Glutathione/metabolism
4-chloro-1,2-phenylenediamine induces apoptosis in Mardin-Darby canine kidney cells via activation of caspases

Onn LC, Ching CS, Lian TY, Foon LV, Chew Hee N, Moi CS

Environ Toxicol, 2014 Jun;29(6):655-64.
PMID: 22778066 DOI: 10.1002/tox.21792

4-Chloro-1,2-phenylenediamine (4-Cl-o-PD) is a halogenated aromatic diamine that was used as a precursor for manufacturing permanent hair dyes. Despite its well-documented mutagenic and carcinogenic effects in a number of in vitro and in vivo models, its cytotoxicity and mode of action have not received similar attention. Here, we investigated the effect of 4-Cl-o-PD on Mardin-Darby canine kidney cells. It induced apoptosis and the evidence suggests its initiation by reactive oxygen species (ROS). The results of various assays used show a dose-dependent (i) decrease in cell viability, (ii) increase in cells at sub-G1 phase and the G0/G1 phase arrested in cell cycle, (iii) increase in intracellular ROS accompanied by depletion of glutathione, and (iv) that apoptotic cell death probably involves activation of both intrinsic and extrinsic pathways.

Matched MeSH terms: Glutathione/metabolism
Fulltext Effect of Eurycoma longifolia extract on the Glutathione level in Plasmodium falciparum infected erythrocytes in vitro

Mohd Ridzuan MA, Noor Rain A, Zhari I, Zakiah I

Trop Biomed, 2005 Dec;22(2):155-63.
PMID: 16883282 MyJurnal

In the present study we examined the effect of E. longifolia methanol extract (TA164) on the GSH levels of P. falciparum infected erythrocytes and uninfected erythrocytes. Our study on parasite growth shows the IC50 and IC75 values of TA164 to be 0.17 g/ml and 6 g/ml respectively while for BSO was 25.5 g/ml and 46.5 g/ml respectively. About 95% to 100% growth inhibition of P. falciparum infected erythrocyte was observed when treated with TA164 and BSO at 16 g/ml and 64 g/ml respectively. The study on GSH contents indicated that non-infected erythrocytes treated with 6 g/ml (IC75 values) of TA164 at 24 hours incubation showed less GSH content as compared to non-treated erythrocytes. A similar observation was seen on treated trophozoite infected erythrocyte (10% parasitemia) when treated with 6 g/ml at 3 hours incubation. Analysis of the GSH contents of parasite compartments treated with TA164 at the same concentration (6 g/ml) for 3 hours incubation indicated a reduction of GSH contents. At the same concentration, TA164 did not affect the GSH contents of enriched trophozoite infected erythrocytes (60-70% parasitemia). TA164 did affect the GSH content of non-infected erythrocyte at 24 hours (accept IC50 value) as well as the parasite compartments (trophozoite infected erythrocyte and parasite itself) but fails to affect the GSH content of enriched trophozoite infected erythrocyte.

Matched MeSH terms: Glutathione/metabolism*
Fulltext Increased carbon dioxide concentration improves the antioxidative properties of the Malaysian herb kacip fatimah (Labisia pumila Blume)

Ibrahim MH, Jaafar HZ

Molecules, 2011 Jul 20;16(7):6068-81.
PMID: 21775936 DOI: 10.3390/molecules16076068

A randomized complete randomized design (RCBD) 3 by 3 experiment was designed to investigate and distinguish the relationships among production of secondary metabolites (total phenolics, TP; total flavonoids, TF), gluthatione (GSH), oxidized gluthatione (GSSG), soluble carbohydrate and antioxidant activities of the Malaysian medicinal herb Labisia pumila Blume under three levels of CO₂ enrichment (400, 800 and 1,200 µmol mol⁻¹) for 15 weeks. It was found that the treatment effects were solely contributed by interaction of CO₂ levels and secondary metabolites distribution in plant parts, GSH, GSHH and antioxidant activities (peroxyl radicals (ROO), superoxide radicals (O₂), hydrogen peroxide (H₂O₂) and hydroxyl radicals (OH). The records of secondary metabolites, glutahione, oxidized gluthathione and antioxidant activities in a descending manner came from the leaf enriched with 1,200 µmol/mol CO₂ > leaf 800 µmol/mol CO₂ > leaf 400 µmol/mol CO₂ > stem 1,200 µmol/mol CO₂ > stem 800 µmol/mol CO₂ > stem 400 µmol/mol CO₂ > root 1,200 µmol/mol CO₂ > root 800 µmol/mol CO₂ > root 400 µmol/mol CO₂. Correlation analyses revealed strong significant positive coefficients of antioxidant activities with total phenolics, flavonoids, GSH and GSHH indicating that an increase in antioxidative activity of L. pumila under elevated CO₂ might be up-regulated by the increase in production of total phenolics, total flavonoids, GSH, GSHH and soluble sugar. This study implied that the medicinal potential of herbal plant such as L. pumila can be enhanced under elevated CO₂, which had simultaneously improved the antioxidative activity that indicated by the high oxygen radical absorbance activity against ROO, O₂, H₂O₂, and OH radicals.

Matched MeSH terms: Glutathione/metabolism
Fulltext Effects of 1-methylcyclopropene and modified atmosphere packaging on the antioxidant capacity in pepper "Kulai" during low-temperature storage

Tan CK, Ali ZM, Ismail I, Zainal Z

ScientificWorldJournal, 2012;2012:474801.
PMID: 22919322 DOI: 10.1100/2012/474801

The objective of the present study was to simultaneously evaluate the effect of a postharvest treatment on the pepper's antioxidant content and its ability to retain its economical value during the postharvest period. The fruits were pretreated by modified atmosphere packaging (MAP) with or without treatment with 1-methylcyclopropene (1-MCP) before cold storage at 10°C. Changes in the levels of non-enzymatic antioxidants, including the total phenolic, ascorbic acid levels and the total glutathione level, as well as enzymatic antioxidants, including ascorbate peroxidase (APX), glutathione reductase (GR), and catalase (CAT), were determined. Both treatments successfully extended the shelf life of the fruit for up to 25 days, and a high level of antioxidant capacity was maintained throughout the storage period. However, 1-MCP treatment maintained the high antioxidant capacity for a longer period of time. The 1-MCP-treated peppers maintained high levels of phenolic content, a high reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio, decreased levels of ascorbic acid and CAT activity, and increased levels of APX and GR compared with the peppers that were not treated with 1-MCP. The overall results suggested that a combination of 1-MCP and MAP was the most effective treatment for extending shelf life while retaining the nutritional benefits.

Matched MeSH terms: Glutathione/metabolism
Glutathione conjugation of nitrogen mustards: In vitro study

Hamzah N, Kjellberg M, Vanninen P

Rapid Commun Mass Spectrom, 2023 May 15;37(9):e9495.
PMID: 36799074 DOI: 10.1002/rcm.9495

RATIONALE: This paper describes an in vitro study designed to identify metabolic biomarkers resulting from the conjugation of nitrogen mustards (NMs) with glutathione (GSH). The method developed is essential in providing evidence in the event of NM exposure in biomedical samples.
METHODS: The mass spectral characterization of the proposed NMs-GSH conjugates was performed with liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). The final reaction mixtures were analysed in positive electrospray ionisation (ESI) at different incubation times.
RESULTS: This study identified three types of conjugates in addition to ethanolamines, the hydrolysis products of NMs. Monoglutathionyl, diglutathionyl and phosphorylated conjugates were produced for each of the NMs, bis(2-chloroethyl)ethylamine (HN1), bis(2-chloroethyl)methylamine (HN2) and tris(2-chloroethyl)amine (HN3). The monoglutathionyl conjugates consisted of HN1-GSH, HN2-GSH and HN3-GSH. The spontaneous and primary conjugates of diglutathionyl were HN1-GSH2, HN2-GSH2 and HN3-GSH2. These included phosphorylated conjugates, namely HN1-GSH-PO4 , HN2-GSH-PO4 and HN3-GSH-PO4 , as might have formed due to hydrolysis in phosphate buffer.
CONCLUSIONS: The mass spectral data of all conjugates formed in the presence of all NMs and GSH are reported in this study. These GSH metabolites can be used to confirm NMs toxicity in biological samples such as urine.

Matched MeSH terms: Glutathione/metabolism
Development and application of fragment-based de novo inhibitor design approaches against Plasmodium falciparum GST

Al-Qattan MNM, Mordi MN

J Mol Model, 2023 Aug 16;29(9):281.
PMID: 37584781 DOI: 10.1007/s00894-023-05650-0

CONTEXT: Modulation of disease progression is frequently started by identifying biochemical pathway catalyzed by biomolecule that is prone to inhibition by small molecular weight ligands. Such ligands (leads) can be obtained from natural resources or synthetic libraries. However, de novo design based on fragments assembly and optimization is showing increasing success. Plasmodium falciparum parasite depends on glutathione-S-transferase (PfGST) in buffering oxidative heme as an approach to resist some antimalarials. Therefore, PfGST is considered an attractive target for drug development. In this research, fragment-based approaches were used to design molecules that can fit to glutathione (GSH) binding site (G-site) of PfGST.
METHODS: The involved approaches build molecules from fragments that are either isosteric to GSH sub-moieties (ligand-based) or successfully docked to GSH binding sub-pockets (structure-based). Compared to reference GST inhibitor of S-hexyl GSH, ligands with improved rigidity, synthetic accessibility, and affinity to receptor were successfully designed. The method involves joining fragments to create ligands. The ligands were then explored using molecular docking, Cartesian coordinate's optimization, and simplified free energy determination as well as MD simulation and MMPBSA calculations. Several tools were used which include OPENEYE toolkit, Open Babel, Autodock Vina, Gromacs, and SwissParam server, and molecular mechanics force field of MMFF94 for optimization and CHARMM27 for MD simulation. In addition, in-house scripts written in Matlab were used to control fragments connection and automation of the tools.

Matched MeSH terms: Glutathione/metabolism

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