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Hepatoprotective effect of Cymbopogon citratus aqueous extract against hydrogen peroxide-induced liver injury in male rats

Rahim SM, Taha EM, Al-janabi MS, Al-douri BI, Simon KD, Mazlan AG

Afr J Tradit Complement Altern Med, 2014;11(2):447-51.
PMID: 25435631

BACKGROUND: Cymbopogon citratus (Poaceae) a tropical perennial herb plant that is widely cultivated to be eaten either fresh with food or dried in tea or soft drink has been reported to possess a number of medicinal and aromatic properties. This study aimed at evaluating the protective effects of C. citratus aqueous extract against liver injury induced by hydrogen peroxide (H2O2), in male rats.
MATERIALS AND METHODS: Twenty-five rats were randomly divided into five different groups of five animals in each group; (1) Control. (2) Received H2O2 (0.5%) with drinking water. (3), and (4) received H2O2 and C. citratus (100 mg·kg(-1) b wt), vitamin C (250 mg·kg(-1) b wt) respectively. (5), was given C. citratus alone. The treatments were administered for 30 days. Blood samples were collected and serum was used for biochemical assay including liver enzymes activities, total protein, total bilirubin and malonaldehyde, glutathione in serum and liver homogenates. Liver was excised and routinely processed for histological examinations.
RESULTS: C. citratus attenuated liver damage due to H2O2 administration as indicated by the significant reduction (p<0.05), in the elevated levels of ALT, AST, ALP, LDH, TB, and MDA in serum and liver homogenates; increase in TP and GSH levels in serum and liver homogenates; and improvement of liver histo-pathological changes. These effects of the extract were similar to that of vitamin C which used as antioxidant reference.
CONCLUSION: C. citratus could effectively ameliorate H2O2-induced oxidative stress and prevent liver injury in male rats.

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
Relationship between markers of lipid peroxidation, thiol oxidation and Glasgow coma scale scores of moderate head injury patients in the 7 day post-traumatic period

Nayak C, Nayak D, Raja A, Rao A

Neurol Res, 2008 Jun;30(5):461-4.
PMID: 18953735

Epidemiologic works reveal that moderate head injury (MHI) is more frequent and a substantial number of these patients develop complications resulting in neurological disabilities. Reactive oxygen species (ROS) play a major role in post-traumatic neuronal damage following traumatic head injury. Thus, the current study analysed the post-traumatic changes in the erythrocyte markers of oxidative damage and the relationship between these parameters and Glasgow coma scale (GCS) scores of MHI patients during the 7 day study period.

Matched MeSH terms: Glutathione/metabolism*
Fulltext Amelioration of high-fat diet-induced obesity and its associated complications by a myricetin derivative-rich fraction from Syzygium malaccense in C57BL/6J mice

Nallappan D, Chua KH, Ong KC, Chong CW, Teh CSJ, Palanisamy UD, et al.

Food Funct, 2021 Jul 05;12(13):5876-5891.
PMID: 34019055 DOI: 10.1039/d1fo00539a

Obesity is a driving factor in the onset of metabolic disorders. This study aims to investigate the effects of the myricetin derivative-rich fraction (MD) from Syzygium malaccense leaf extract on high-fat diet (HFD)-induced obesity and its associated complications and its influence on uncoupling protein-1 (UCP-1) and gut microbiota in C57BL/6J mice. Mice were randomly assigned into four groups (n = 6) and given a normal diet (ND) or high-fat diet (HFD) for 10 weeks to induce obesity. The HFD groups (continued with HFD) were administered 50 mg kg-1 MD (treatment), 50 mg kg-1 metformin (positive control) and normal saline (HFD and ND controls) daily for four weeks via oral gavage. The ten-week HFD-feeding resulted in hyperglycemia and elevated urinary oxidative indices. The subsequent MD administration caused significant weight reduction without appetite suppression and amelioration of insulin resistance, steatosis and dyslipidemia. Besides, MD significantly reduced lipid hydroperoxides and protein carbonyls in tissue homogenates and urine and elevated Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and reduced glutathione (GSH) and thus, alleviated oxidative stress. The weight reduction was correlated with downregulation of inflammatory markers and the increased UCP-1 level, suggesting weight loss plausibly through thermogenesis. The Akkermansia genus (reflects improved metabolic status) in the HFD50 group was more abundant than that in the HFD group while the non-enzymatic antioxidant markers were strongly associated with UCP-1. In conclusion, MD ameliorates obesity and its related complications possibly via the upregulation of UCP-1 and increased abundance of Akkermansia genus and is promising as a therapeutic agent in the treatment of obesity and its associated metabolic disorders.

Matched MeSH terms: Glutathione/metabolism
Synthesis of α-hydroxyphosphonates and their antioxidant properties

Naidu KR, Kumar KS, Arulselvan P, Reddy CB, Lasekan O

Arch Pharm (Weinheim), 2012 Dec;345(12):957-63.
PMID: 23015406 DOI: 10.1002/ardp.201200192

A series of α-hydroxyphosphonates were synthesized from the reaction of aldehyde (1) with triethylphosphite (2) in the presence of oxone and evaluated for their antioxidant properties against lipid peroxidation, reduced glutathione, superoxide dismutase, and catalase. The majority of the compounds showed promising antioxidant activity. Diethyl anthracen-9-yl (hydroxy) methylphosphonate (3n) is the most potent and biologically active compound against free radicals.

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*
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
Rutin, a bioflavonoid antioxidant protects rat pheochromocytoma (PC-12) cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity

Magalingam KB, Radhakrishnan A, Haleagrahara N

Int J Mol Med, 2013 Jul;32(1):235-40.
PMID: 23670213 DOI: 10.3892/ijmm.2013.1375

Free radicals are widely known to be the major cause of human diseases such as neurodegenerative diseases, cancer, allergy and autoimmune diseases. Human cells are equipped with a powerful natural antioxidant enzyme network. However, antioxidants, particularly those originating from natural sources such as fruits and vegetables, are still considered essential. Rutin, a quercetin glycoside, has been proven to possess antioxidant potential. However, the neuroprotective effect of rutin in pheochromocytoma (PC-12) cells has not been studied extensively. Therefore, the present study was designed to establish the neuroprotective role of rutin as well as to elucidate the antioxidant mechanism of rutin in 6-hydroxydopamine (6-OHDA)-induced toxicity in PC-12 neuronal cells. PC-12 cells were pretreated with different concentrations of rutin for 4, 8 and 12 h and subsequently incubated with 6-OHDA for 24 h to induce oxidative stress. A significant cytoprotective activity was observed in rutin pretreated cells in a dose-dependent manner. Furthermore, there was marked activation of antioxidant enzymes including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and total glutathione (GSH) in rutin pretreated cells compared to cells incubated with 6-OHDA alone. Rutin significantly reduced lipid peroxidation in 6-OHDA-induced PC-12 cells. On the basis of these observations, it was concluded that the bioflavonoid rutin inhibited 6-OHDA-induced neurotoxicity in PC-12 cells by improving antioxidant enzyme levels and inhibiting lipid peroxidation.

Matched MeSH terms: Glutathione/metabolism
Activation of Nrf2 signaling by sitagliptin and quercetin combination against β-amyloid induced Alzheimer's disease in rats

Li Y, Tian Q, Li Z, Dang M, Lin Y, Hou X

Drug Dev Res, 2019 09;80(6):837-845.
PMID: 31301179 DOI: 10.1002/ddr.21567

The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β-amyloid (Aβ) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aβ1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.

Matched MeSH terms: Glutathione/metabolism
Lipid peroxidation and decline in antioxidant status as one of the toxicity measures of diazinon in the testis

Leong CT, D'Souza UJ, Iqbal M, Mustapha ZA

Redox Rep., 2013;18(4):155-64.
PMID: 23849340 DOI: 10.1179/1351000213Y.0000000054

The rapid emergence of various pesticides in the market is inevitable due to the demands from agriculture industries and domestic needs to control nuisance pests and to sustain green resources worldwide. However, long-term exposure to pesticide has led to adverse effects on male fertility. Organophosphate diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphorothiote) is an often abusively used pesticide, as it is effective and economical. This study is to determine the adverse effects of low-dose diazinon exposure on the male reproductive system. In this study, 72 Sprague-Dawley rats were segregated into 1, 2, and 8 weeks of exposure groups and further sub-grouped (n = 6) to receive 0, 10, 15, and 30 mg/kg body weight diazinon treatment. Rats were gavaged orally with diazinon and sacrificed under anaesthesia the day after the last exposure. Our results showed that consistent diazinon exposure decreased glutathione and catalase, and increased lipid peroxidation which together lead to diazinon-mediated oxidative stress. Additionally, diazinon increased serum lactate dehydrogenase and decreased serum testosterone, which may have caused sperm and histopathological anomalies. In conclusion, exposure to diazinon caused changes in lipid peroxidation and sperm, and these two effects might be causally linked.

Matched MeSH terms: Glutathione/metabolism
Glutathione system in young spontaneously hypertensive rats

Lee SK, Arunkumar S, Sirajudeen KN, Singh HJ

J Physiol Biochem, 2010 Dec;66(4):321-7.
PMID: 20680541 DOI: 10.1007/s13105-010-0038-2

Glutathione (GSH) forms a part of the antioxidant system that plays a vital role in preventing oxidative stress, and an imbalance in the oxidant/antioxidant system has been linked to the pathogenesis of hypertension. The aim of this study was to investigate the status of the GSH system in the kidney of spontaneously hypertensive rats (SHR). Components of the GSH system, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and total GSH content, were measured in the kidneys of 4, 6, 8, 12, and 16 weeks old SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure of SHR was significantly higher from the age of 6 weeks onwards compared with age-matched WKY rats. GPx activity in the SHR was significantly lower from the age of 8 weeks onwards when compared to that in age-matched WKY rats. No significant differences were evident in the GPx-1 protein abundance, and its relative mRNA levels, GR, GST activity, and total GSH content between SHR and age-matched WKY rats. The lower GPx activity suggests of an impairment of the GSH system in the SHR, which might be due to an abnormality in its protein rather than non-availability of a cofactor. Its role in the development of hypertension in SHR however remains unclear.

Matched MeSH terms: Glutathione/metabolism*
Therapeutic effect of pectin on octylphenol induced kidney dysfunction, oxidative stress and apoptosis in rats

Koriem KM, Arbid MS, Emam KR

Environ Toxicol Pharmacol, 2014 Jul;38(1):14-23.
PMID: 24860957 DOI: 10.1016/j.etap.2014.04.029

Octylphenol (OP) is one of ubiquitous pollutants in the environment. It belongs to endocrine-disrupting chemicals (EDC). It is used in many industrial and agricultural products. Pectin is a family of complex polysaccharides that function as a hydrating agent and cementing material for the cellulose network. The aim of this study was to evaluate the therapeutic effect of pectin in kidney dysfunction, oxidative stress and apoptosis induced by OP exposure. Thirty-two male albino rats were divided into four equal groups; group 1 control was injected intraperitoneally (i.p) with saline [1 ml/kg body weight (bwt)], groups 2, 3 & 4 were injected i.p with OP (50 mg/kg bwt) three days/week over two weeks period where groups 3 & 4 were injected i.p with pectin (25 or 50 mg/kg bwt) three days/week over three weeks period. The results of the present study revealed that OP significantly decreased glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) levels while increased significantly lipid peroxidation (MDA), nitric oxide (NO) and protein carbonyls (PC) levels in the kidney tissues. On the other hand, OP increased serum urea and creatinine. Furthermore, OP increased significantly serum uric acid but decreased significantly the kidney weight. Moreover, OP decreased p53 expression while increased bcl-2 expression in the kidney tissue. The treatment with either dose of pectin to OP-exposed rats restores all the above parameters to approach the normal values where pectin at higher dose was more effective than lower one. These results were supported by histopathological investigations. In conclusion, pectin has antioxidant and anti-apoptotic activities in kidney toxicity induced by OP and the effect was dose-dependent.

Matched MeSH terms: Glutathione/metabolism
Antioxidant potential of Cymbopogon citratus extract: alleviation of carbon tetrachloride-induced hepatic oxidative stress and toxicity

Koh PH, Mokhtar RA, Iqbal M

Hum Exp Toxicol, 2012 Jan;31(1):81-91.
PMID: 21508074 DOI: 10.1177/0960327111407226

This study was aimed to evaluate the effect of Cymbopogon citratus against carbon tetrachloride (CCl(4))-mediated hepatic oxidative damage in rats. Rats were administrated with C. citratus extract (100, 200 and 300 mg/kg b.w.) for 14 days before the challenge of CCl(4) (1.2 ml/kg b.w. p.o) on 13th and 14th days. Hepatic damage was evaluated by employing serum biochemical parameters (alanine aminotransferase-ALT, aspartate aminotransferase-AST and lactate dehydrogenase-LDH), malondialdehye (MDA) level, reduced GSH and antioxidant enzymes (catalase: CAT, glutathione peroxidase: GPX, quinone reductase: QR, glutathione S-transferase: GST, glutathione reductase: GR, glucose-6-phosphate dehyrogenase: G6PD). In addition, CCl(4)-mediated hepatic damage was further evaluated by histopathological examination. However, most of these changes were alleviated by prophylactic treatment of animals with C. citratus dose dependently (p < 0.05). The protection was further evident through decreased histopathological alterations in liver. The results of the present study indicated that the hepatoprotective effect of C. citratus might be ascribable to its antioxidant and free radical scavenging property.

Matched MeSH terms: Glutathione/metabolism
Andrographis paniculata ameliorates carbon tetrachloride (CCl(4))-dependent hepatic damage and toxicity: diminution of oxidative stress

Koh PH, Mokhtar RA, Iqbal M

Redox Rep., 2011;16(3):134-43.
PMID: 21801496 DOI: 10.1179/1351000211Y.0000000003

Andrographis paniculata (hempedu bumi) is a plant that possesses many medicinal values in treating several diseases and for health care maintenance. However, its hepatoprotective activity and mechanism of action have not been fully investigated. Therefore, this study aimed to evaluate the hepatoprotective effects of A. paniculata and its mechanism of action in rats. Carbon tetrachloride (CCl(4)) challenge of rats at a dose of 1.2 ml/kg body weight-induced oxidative stress in the liver. This was evidenced by augmentation in lipid peroxidation, which was accompanied by a decrease in the activities of antioxidant enzymes and depletion in the level of reduced glutathione (P < 0.05). Parrallel to these changes, CCl(4) challenge too, enhanced hepatic damage as evidenced by sharp increase in serum transaminases (e.g. alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) (P < 0.05). Additionally, the impairment of liver function corresponded to histolopathological changes. However, most of these changes were reversed in a dose-dependent fashion by pre-treatment of animals with A. paniculata (P < 0.05). The ability of A. paniculata to scavenge the 2,2-Diphenyl-2-picrylhydrazyl radical was determined through its EC(50) value. The EC(50) value of A. paniculata was 583.60 ± 4.25 µg/ml. In addition, A. paniculata was found to contain 65.37 ± 1.20 mg/g total phenolics expressed as gallic acid equivalent. From these studies, it is concluded that A. paniculata could be used as a hepatoprotective agent and possesses the potential to treat or prevent degenerative diseases where oxidative stress is implicated.

Matched MeSH terms: Glutathione/metabolism
Fulltext Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts

Khor SC, Wan Ngah WZ, Mohd Yusof YA, Abdul Karim N, Makpol S

Oxid Med Cell Longev, 2017;2017:3868305.
PMID: 28243354 DOI: 10.1155/2017/3868305

During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF) and N-acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPX1) was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts.

Matched MeSH terms: Glutathione/metabolism
Oxidised low density lipoprotein causes human macrophage cell death through oxidant generation and inhibition of key catabolic enzymes

Katouah H, Chen A, Othman I, Gieseg SP

Int J Biochem Cell Biol, 2015 Oct;67:34-42.
PMID: 26255116 DOI: 10.1016/j.biocel.2015.08.001

Oxidised low density lipoprotein (oxLDL) is thought to be a significant contributor to the death of macrophage cells observed in advanced atherosclerotic plaques. Using human-derived U937 cells we have examined the effect of cytotoxic oxLDL on oxidative stress and cellular catabolism. Within 3h of the addition of oxLDL, there was a rapid, concentration dependent rise in cellular reactive oxygen species followed by the loss of cellular GSH, and the enzyme activity of both glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aconitase. The loss of these catabolic enzymes was accompanied by the loss of cellular ATP and lower lactate generation. Addition of the macrophage antioxidant 7,8-dihydroneopterin inhibited the ROS generation, glutathione loss and catabolic inactivation. NOX was shown to be activated by oxLDL addition while apocynin inhibited the loss of GSH and cell viability. The data suggests that oxLDL triggers an excess of ROS production through NOX activation, and catabolic failure through thiol oxidation resulting in cell death.

Matched MeSH terms: Glutathione/metabolism
The effects of intramuscular and intraperitoneal injections of benzo[a]pyrene on selected biomarkers in Clarias gariepinus

Karami A, Christianus A, Ishak Z, Syed MA, Courtenay SC

Ecotoxicol Environ Saf, 2011 Sep;74(6):1558-66.
PMID: 21636131 DOI: 10.1016/j.ecoenv.2011.05.012

This study investigated the dose-dependent and time-course effects of intramuscular (i.m.) and intraperitoneal (i.p.) injection of benzo[a]pyrene (BaP) on the biomarkers EROD activity, GST activity, concentrations of BaP metabolites in bile, and visceral fat deposits (Lipid Somatic Index, LSI) in African catfish (Clarias gariepinus). Intraperitoneal injection resulted in 4.5 times higher accumulation of total selected biliary FACs than i.m. injection. Hepatic GST activities were inhibited by BaP via both injection methods. Dose-response relationships between BaP injection and both biliary FAC concentrations and hepatic GST activities were linear in the i.p. injected group but nonlinear in the i.m. injected fish. Hepatic EROD activity and LSI were not significantly affected by BaP exposure by either injection route. We conclude that i.p. is a more effective route of exposure than i.m. for future ecotoxicological studies of PAH exposure in C. gariepinus.

Matched MeSH terms: Glutathione/metabolism
The selective cytotoxicity of the alkenyl glucosinolate hydrolysis products and their presence in Brassica vegetables

Kadir NH, David R, Rossiter JT, Gooderham NJ

Toxicology, 2015 Aug 6;334:59-71.
PMID: 26066520 DOI: 10.1016/j.tox.2015.06.002

Cruciferous vegetable consumption correlates with reduced risk of cancer. This chemopreventative activity may involve glucosinolates and their hydrolysis products. Glucosinolate-derived isothiocyanates have been studied for their toxicity and chemopreventative properties, but other hydrolysis products (epithionitriles and nitriles) have not been thoroughly examined. We report that these hydrolysis products differ in their cytotoxicity to human cells, with toxicity most strongly associated with isothiocyanates rather than epithionitriles and nitriles. We explored mechanisms of this differential cytotoxicity by examining the role of oxidative metabolism, oxidative stress, mitochondrial permeability, reduced glutathione levels, cell cycle arrest and apoptosis. 2-Propenylisothiocyanate and 3-butenylisothiocyanate both inhibited cytochome P450 1A (CYP1A) enzyme activity in CYP expressing MCL-5 cells at high cytotoxic doses. Incubation of MCL-5 cells with non-cytotoxic doses of 2-propenylisothiocyanate for 24h resulted in a dose-dependent inhibition of ethoxyresorufin O-deethylase, yet failed to affect CYP1A1 mRNA expression indicating interference with enzyme activity rather than inhibition of transcription. Increased reactive oxygen species (ROS) production was observed only for 2-propenylisothiocyanate treatment. 2-Propenylisothiocyanate treatment lowered reduced glutathione levels whereas no changes were noted with 3,4-epithiobutylnitrile. Cell cycle analysis showed that 2-propenylisothiocyanate induced a G2/M block whereas other hydrolysis products showed only marginal effects. We found that 2-propenylisothiocyanate and 3-butenylisothiocyanate induced cell death predominantly via necrosis whereas, 3,4-epithiobutylnitrile promoted both necrosis and apoptosis. Thus the activity of glucosinolate hydrolysis products includes cytotoxicity that is compound-class specific and may contribute to their putative chemoprotection properties.

Matched MeSH terms: Glutathione/metabolism
Light-harvesting complexes in photosystem II regulate glutathione-induced sensitivity of Arabidopsis guard cells to abscisic acid

Jahan MS, Nozulaidi M, Khairi M, Mat N

J Plant Physiol, 2016 May 20;195:1-8.
PMID: 26970687 DOI: 10.1016/j.jplph.2016.03.002

Light-harvesting complexes (LHCs) in photosystem II (PSII) regulate glutathione (GSH) functions in plants. To investigate whether LHCs control GSH biosynthesis that modifies guard cell abscisic acid (ABA) sensitivity, we evaluated GSH content, stomatal aperture, reactive oxygen species (ROS), weight loss and plant growth using a ch1-1 mutant that was defective of LHCs and compared this with wild-type (WT) Arabidopsis thaliana plants. Glutathione monoethyl ester (GSHmee) increased but 1-chloro-2,4 dinitrobenzene (CDNB) decreased the GSH content in the guard cells. The guard cells of the ch1-1 mutants accumulated significantly less GSH than the WT plants. The guard cells of the ch1-1 mutants also showed higher sensitivity to ABA than the WT plants. The CDNB treatment increased but the GSHmee treatment decreased the ABA sensitivity of the guard cells without affecting ABA-induced ROS production. Dark and light treatments altered the GSH content and stomatal aperture of the guard cells of ch1-1 and WT plants, irrespective of CDNB and GSHmee. The ch1-1 mutant contained fewer guard cells and displayed poor growth, late flowering and stumpy weight loss compared with the WT plants. This study suggests that defective LHCs reduced the GSH content in the guard cells and increased sensitivity to ABA, resulting in stomatal closure.

Matched MeSH terms: Glutathione/metabolism
Fulltext Goniothalamin-induced oxidative stress, DNA damage and apoptosis via caspase-2 independent and Bcl-2 independent pathways in Jurkat T-cells

Inayat-Hussain SH, Chan KM, Rajab NF, Din LB, Chow SC, Kizilors A, et al.

Toxicol Lett, 2010 Mar 1;193(1):108-14.
PMID: 20026395 DOI: 10.1016/j.toxlet.2009.12.010

Goniothalamin (GTN) isolated from Goniothalamus sp. has been demonstrated to induce apoptosis in a variety of cancer cell lines including Jurkat T leukemia cells. However, the mechanism of GTN-induced apoptosis upstream of mitochondria is still poorly defined. In this study, GTN caused a decrease in GSH with an elevation of reactive oxygen species as early as 30 min and DNA damage as assessed by Comet assay. Analysis using topoisomerase II processing of supercoiled pBR 322 DNA showed that GTN caused DNA damage via a topoisomerase II-independent pathway suggesting that cellular oxidative stress may contribute to genotoxicity. A 12-fold increase of caspase-2 activity was observed in GTN-treated Jurkat cells after 4h treatment and this was confirmed using Western blotting. Although the caspase-2 inhibitor Z-VDVAD-FMK inhibited the proteolytic activity of caspase-2, apoptosis ensued confirming that caspase-2 activity was not crucial for GTN-induced apoptosis. However, GTN-induced apoptosis was completely abrogated by N-acetylcysteine further confirming the role of oxidative stress. Since cytochrome c release was observed as early as 1h without any appreciable change in Bcl-2 protein expression, we further investigated whether overexpression of Bcl-2 confers resistance in GTN-induced cytotoxicity. Using a panel of Jurkat Bcl-2 transfectants, GTN cytotoxicity was not abrogated in these cells. In conclusion, GTN induces DNA damage and oxidative stress resulting in apoptosis which is independent of both caspase-2 and Bcl-2.

Matched MeSH terms: Glutathione/metabolism

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