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Fulltext α -Mangostin from Cratoxylum arborescens (Vahl) Blume Demonstrates Anti-Ulcerogenic Property: A Mechanistic Study

Sidahmed HM, Abdelwahab SI, Mohan S, Abdulla MA, Mohamed Elhassan Taha M, Hashim NM, et al.

Evid Based Complement Alternat Med, 2013;2013:450840.
PMID: 23634169 DOI: 10.1155/2013/450840

Cratoxylum arborescens (Vahl) Blume is an Asian herbal medicine with versatile ethnobiological properties including treatment of gastric ulcer. This study evaluated the antiulcerogenic mechanism(s) of α -mangostin (AM) in a rat model of ulcer. AM is a prenylated xanthone derived through biologically guided fractionation of C. arborescens. Rats were orally pretreated with AM and subsequently exposed to acute gastric lesions induced by ethanol. Following treatment, ulcer index, gastric juice acidity, mucus content, histological and immunohistochemical analyses, glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and nonprotein sulfhydryl groups (NP-SH) were evaluated. The anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitory effect, and antioxidant activity of AM were also investigated in vitro. AM (10 and 30 mg/kg) inhibited significantly (P < 0.05) ethanol-induced gastric lesions by 66.04% and 74.39 %, respectively. The compound induces the expression of Hsp70, restores GSH levels, decreases lipid peroxidation, and inhibits COX-2 activity. The minimum inhibitory concentration (MIC) of AM showed an effective in vitro anti-H. pylori activity. The efficacy of the AM was accomplished safely without presenting any toxicological parameters. The results of the present study indicate that the antioxidant properties and the potent anti-H. pylori, in addition to activation of Hsp70 protein, may contribute to the gastroprotective activity of α -mangostin.

Matched MeSH terms: Glutathione
[FEATURES MANIFESTATIONS COMORBID CURRENTS OF GASTROESOPHAGEAL REFLUX DISEASE AND ARTERIAL HYPERTENSION DEPENDING ON THE DEGREE OF ARTERIAL HYPERTENSION]

Fadieienko G, Gridniev O

Georgian Med News, 2015 Nov.
PMID: 26656546

The purpose of research - to study the features of circadian profile of blood pressure (BP), the data of echocardiography, pH-monitoring, lipid spectrum, level of apelin and the state of the system "lipid peroxidation-antioxidant protection" in patients with a combination of arterial hypertension (AH) and gastroesophageal reflux disease (GERD) depending on the level of AH. It was examined 126 patients with combination of AH II stage, 2-3 degrees, and GERD, 70 (55.56%) men and 56 (44.44%) women, mean age 56.84 ± 1.17. The anthropometric indicators, a condition of "lipid peroxidation- antioxidant protection", the level of apelin, ambulatory blood pressure monitoring (ABPM), echocardiography, esophageal pH-monitoring were evaluated. Analysis of the results was performed using a computer program IBM SPSS Statistics 21.0 for Windows XP. According to the daily averages ABPM systolic BP/diastolic BP in the I group were 141.2 ± 0.8/90.4 ± 0.4 mm Hg., in II group - 163.3 ± 0.9/101.0 ± 0.5 mm Hg., in III group - 185.6 ± 0.8/112.1 ± 0.5 mm Hg., p = 0.001. There are only 25.39% of patients had normal indicators of the variability of BP among individuals with comorbidity. Transformation from mild AH to moderate was accompanied by a significant increase in the severity of left ventricular remodeling by type of concentric hypertrophy. The data of esophageal pH-monitoring allow us to classify the disorders as severe gastroesophageal reflux in patients with a combination of AH and GERD (DeMeester, 1993). In the group with first degree of AH the average rate of circulating apelin was 930.58 ± 56.27 pg/mL, for the patients with 2nd degree of AH - 880.56 ± 17.97 pg/ml, p>0.05, in patients with third degree of AH - 650.91 ± 12.87 pg/ml (p = 0.001). Assessment of lipid profile has allowed to establish the worse dyslipidemia in patients with 3rd degree of AH combined with GERD (atherogenic ratio - 3.11 ± 0.09). The deterioration of degree of AH combined with GERD accompanied by an increase of oxidative stress with increase of nitrites plasma and malondialdehyde concentration, and decrease of glutathione peroxidase and of SH-groups concentration. Increased degree of AH in patients with severe GERD accompanied by worsening of left ventricular remodeling, reduction of apelin levels, progression of dyslipidemia, and imbalances in the system of "lipid peroxidation-antioxidant protection."

Matched MeSH terms: Glutathione Peroxidase/blood
Vitamin E, glutathione S-transferase and gamma-glutamyl transpeptidase activities in cultured hepatocytes of rats treated with carcinogens

Ong FB, Wan Ngah WZ, Top AG, Khalid BA, Shamaan NA

Int. J. Biochem., 1994 Mar;26(3):397-402.
PMID: 7910569

1. The effects of alpha-tocopherol and gamma-tocotrienol on glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT) activities in cultured hepatocytes prepared from rats treated with diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated. 2. Both the alpha-tocopherol and gamma-tocotrienol treated hepatocytes showed significantly higher (P < 0.05) GST activities than untreated hepatocytes prepared from the carcinogen treated rats in the first 3 days of culture. Treatment with alpha-tocopherol and gamma-tocotrienol generally resulted in a tendency to increase the GST activities above that in the untreated hepatocytes. 3. Treatment with high doses (125-250 microM) of alpha-tocopherol and low doses (12.5-25 microM) of gamma-tocotrienol generally resulted in a significant reduction in gamma-GT activities at 1-3 days. gamma-GT activities are reduced as the dose of alpha-tocopherol and gamma-tocotrienol are increased.

Matched MeSH terms: Glutathione Transferase/metabolism*
Vitamin C and aloe vera supplementation protects from chemical hepatocarcinogenesis in the rat

Shamaan NA, Kadir KA, Rahmat A, Ngah WZ

Nutrition, 1998 12 3;14(11-12):846-52.
PMID: 9834927

The effects of vitamin C and aloe vera gel extract supplementation on induced hepatocarcinogenesis in male Sprague-Dawley rats (120-150 g) by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) was investigated. The severity of the carcinogenesis process was determined by measuring gamma-glutamyl transpeptidase (GGT) and the placental form of glutathione S-transferase (GSTP) histochemically in situ and in plasma and liver fractions. In addition, plasma alkaline phosphatase (ALP) and liver microsomal uridine diphosphate glucuronyl transferase (UDPGT) activity were also determined. Administration of DEN/AAF caused an increase in the surface area and number of enzyme-positive foci (both GGT and GSTP) compared with control. Supplementation of vitamin C or aloe vera gel extract to the cancer-induced rats suppressed this increase significantly (P < 0.05; P < 0.001). Increases in liver UDPGT, GGT, and GSTP activities were also observed with cancer induction that were again suppressed with either vitamin C or aloe vera gel supplementation. Plasma GGT in the DEN/AAF rats were determined monthly for the duration of the experiment and found to be reduced as early as 1 mo with aloe vera gel supplementation and 2 mo with vitamin C supplementation. In conclusion, vitamin C and aloe vera gel extract supplementation were found to be able to reduce the severity of chemical hepatocarcinogenesis.

Matched MeSH terms: Glutathione Transferase/metabolism
Use of intestinal Pseudomonas aeruginosa in fish to detect the environmental pollutant benzo[a]pyrene

Karami A, Christianus A, Ishak Z, Shamsuddin ZH, Masoumian M, Courtenay SC

J Hazard Mater, 2012 May 15;215-216:108-14.
PMID: 22417397 DOI: 10.1016/j.jhazmat.2012.02.038

This study examined the potential of Pseudomonas aeruginosa abundance in the intestines of fish as an indicator of exposure to benzo[a]pyrene (BaP). P. aeruginosa populations were enumerated in juvenile African catfish (Clarias gariepinus) injected intramuscularly three days previous with 0, 10, 30, 40, 50 or 70mg/kg of BaP. Hepatic EROD and GST activities and biliary fluorescent aromatic compounds (FACs) 1-OH BaP, 3-OH BaP, 7,8-D BaP and BaP were quantified to investigate agreements between the new indicator and established fish biomarkers. The shape of bacterial population (logarithm of colony-forming unit) dose-response curve generally matched those of biliary FACs concentrations. Conversely, the EROD and GST dose-response curves were generally the mirror images of the bacterial population curve. Changes in intestinal P. aeruginosa population appear to be an indirect effect of BaP exposure because exposure to 0-100μg/ml BaP had no effect on P. aeruginosa populations grown on agar plates containing BaP. Using intestinal P. aeruginosa population of fish as a universal indicator of BaP pollution in aquatic environments is discussed.Conversely, the EROD and GST dose-response curves were generally the mirror images of the bacterial population curve.

Matched MeSH terms: Glutathione Transferase/metabolism
Upregulation of catalase and downregulation of glutathione peroxidase activity in the kidney precede the development of hypertension in pre-hypertensive SHR

Sundaram A, Siew Keah L, Sirajudeen KN, Singh HJ

Hypertens Res, 2013 Mar;36(3):213-8.
PMID: 23096233 DOI: 10.1038/hr.2012.163

Although oxidative stress has been implicated in the pathogenesis of hypertension in spontaneously hypertensive rats (SHRs), there is little information on the levels of primary antioxidant enzymes status (AOEs) in pre-hypertensive SHR. This study therefore determined the activities of primary AOEs and their mRNA levels, levels of hydrogen peroxide (H2O2), malondialdehyde (MDA) and total antioxidant status (TAS) in whole kidneys of SHR and age-matched Wistar-Kyoto (WKY) rats aged between 2 and 16 weeks. Compared with age-matched WKY rats, catalase (CAT) activity was significantly higher from the age of 2 weeks (P<0.001) and glutathione peroxide (GPx) activity was lower from the age of 3 weeks (P<0.001) in SHR. CAT mRNA levels were significantly higher in SHR aged 2, 4, 6 and 12 weeks. GPx mRNA levels were significantly lower in SHR at 8 and 12 weeks. Superoxide dismutase activity or its mRNA levels were not different between the two strains. H2O2 levels were significantly lower in SHR from the age of 8 weeks (P<0.01). TAS was significantly higher in SHR from the age of 3 weeks (P<0.05). MDA levels were only significantly higher at 16 weeks of age in the SHR (P<0.05). The data suggest that altered renal CAT and GPx mRNA expression and activity precede the development of hypertension in SHR. The raised CAT activity perhaps contributes to the higher TAS and lower H2O2 levels in SHR. In view of these findings, the precise role of oxidative stress in the pathogenesis of hypertension in SHR needs to be investigated further.

Matched MeSH terms: Glutathione Peroxidase/genetics; Glutathione Peroxidase/metabolism*
Fulltext Unstable haemoglobin Köln disease in members of a Malay family

Eng LL, Lopez CG, Eapen JS, Eravelly J, Wiltshire BG, Lehmann H

J Med Genet, 1972 Sep;9(3):340-3.
PMID: 5079107 DOI: 10.1136/jmg.9.3.340
Matched MeSH terms: Glutathione
Tryptophan-tagged peptide from serine threonine-protein kinase of Channa striatus improves antioxidant defence in L6 myotubes and attenuates caspase 3-dependent apoptotic response in zebrafish larvae

Issac PK, Lite C, Guru A, Velayutham M, Kuppusamy G, Saraswathi NT, et al.

Fish Physiol Biochem, 2021 Apr;47(2):293-311.
PMID: 33394283 DOI: 10.1007/s10695-020-00912-7

This study reports the antioxidant property and molecular mechanism of a tryptophan-tagged peptide derived from a teleost fish Channa striatus of serine threonine-protein kinase (STPK). The peptide was tagged with tryptophan to enhance the antioxidant property of STPK and named as IW13. The antioxidant activity of IW13 peptide was investigated using in vitro methods such as DPPH, ABTS, superoxide anion radical scavenging and hydrogen peroxide scavenging assay. Furthermore, to investigate the toxicity and dose response of IW13 peptide on antioxidant defence in vitro, L6 myotubes were induced with generic oxidative stress due to exposure of hydrogen peroxide (H2O2). IW13 peptide exposure was found to be non-cytotoxic to L6 cells in the tested concentration (10, 20, 30, 40 and 50 μM). Also, the pre-treatment of IW13 peptide decreased the lipid peroxidation level and increased glutathione enzyme activity. IW13 peptide treatment upregulated the antioxidant enzyme genes: GPx (glutathione peroxidase), GST (glutathione S transferase) and GCS (glutamine cysteine synthase), in vitro in L6 myotubes and in vivo in zebrafish larvae against the H2O2-induced oxidative stress. The results demonstrated that IW13 renders protection against the H2O2-induced oxidative stress through a cellular antioxidant defence mechanism by upregulating the gene expression, thus enhancing the antioxidant activity in the cellular or organismal level. The findings exhibited that the tryptophan-tagged IW13 peptide from STPK of C. striatus could be a promising candidate for the treatment of oxidative stress-associated diseases.

Matched MeSH terms: Glutathione; Glutathione Peroxidase; Glutathione Transferase
Fulltext Trihoney reduces lipid peroxidation and enhances antioxidant enzyme activities in hypercholesterolaemic atherosclerotic rabbits

Alfarisi, H. A. H., Ibrahim, M.,, Mohamed, Z. B. H., Hamdan, A. H., Che Mohamad, C. A.

International Food Research Journal, 2020;27(3):568-575.
MyJurnal

Oxidative stress and reactive oxygen species (ROS) constitute a major pathogenic mechanism
for the development of atherosclerosis. In the present work, the antioxidant potential of
Trihoney was investigated in hypercholesterolaemic rabbits. Thirty-six male New Zealand
white (NZW) rabbits were grouped into: normal diet (C), normal diet with 0.6 g/kg/day of
Trihoney (C+H), 1% cholesterol diet (HCD), 1% cholesterol diet with 0.3 g/kg/day of
Trihoney (HCD+H1
), 1% cholesterol diet with 0.6 g/kg/day of Trihoney (HCD+H2
), and 1%
cholesterol diet with 2 mg/kg/day of atorvastatin (HCD+At.). Animals were sacrificed following 12 weeks of treatment, and their serum was analysed for oxidised-low density lipoprotein
(Ox-LDL). Serum and aortic tissue homogenate were assayed for superoxide dismutase
(SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Hypercholesterolemia
caused a significant (p < 0.05) elevation in serum Ox-LDL and a significant (p < 0.05) reduction of antioxidant enzyme activities in serum of the HCD group. Trihoney induced a significant (p < 0.05) increase in antioxidant enzyme activities in serum as compared to the HCD
group. The high cholesterol diet suppressed both antioxidant enzymes in aortic homogenate.
Trihoney significantly (p < 0.05) enhanced both antioxidant enzymes in aortic homogenate.
Hypercholesterolemia induced a significant (p < 0.05) elevation of serum lipid peroxidation in
the HCD group. Trihoney caused a significant (p < 0.05) reduction of lipid peroxidation in
aortic homogenate. These results demonstrated that Trihoney has the potential to ameliorate
oxidative stress systemically, as well as locally in the atherosclerotic aorta.

Matched MeSH terms: Glutathione Peroxidase
Fulltext Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease

Anwar F, Saleem U, Rehman AU, Ahmad B, Froeyen M, Mirza MU, et al.

Front Pharmacol, 2021;12:607026.
PMID: 34040515 DOI: 10.3389/fphar.2021.607026

The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a significant rise in Alkaline Phosphatases (ALP), bilirubin, white blood cells (WBC), and lymphocyte levels with a decrease in platelet count. Furthermore, the reduction in urea, uric acid, and aspartate transaminase (AST) levels and an increase in total protein levels were measured in subacute toxicity. SF1 increased spermatogenesis at 5 and 10 mg/kg doses. Teratogenicity study depicted no resorptions, early abortions, cleft palate, spina bifida and any skeletal abnormalities in the fetuses. Oxidative stress markers (Superoxide dismutase (SOD), Catalase (CAT), and glutathione (GSH) were increased in all the experiments, whereas the effect on melanoaldehyde Malondialdehyde (MDA) levels was variable. Histopathology further corroborated these results with no change in the architectures of selected organs. Consequently, a 2000 mg/kg dose of SF1 tends to induce minor liver dysfunction along with immunomodulation, and it is well below its LD
50
. Moreover, it can be safely used in pregnancy owing to its no detectable teratogenicity.

Matched MeSH terms: Glutathione
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
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
Time-relative changes in the erythrocyte antioxidant enzyme activities and their relationship with Glasgow Coma Scale scores in severe head injury patients in the 21-day posttraumatic study period

Nayak CD, Nayak DM, Raja A, Rao A

Indian J Med Sci, 2007 Jul;61(7):381-9.
PMID: 17611343

BACKGROUND: Reactive oxygen species are indicated to play a prime role in the pathophysiology of brain damage following a severe head injury (SHI).
AIM: The current study was designed to understand the time-relative changes and relationship between erythrocyte antioxidant enzyme activities and Glasgow Coma Scale (GCS) scores of SHI patients in the 21-day posttraumatic study period.
SETTINGS AND DESIGN: The study included 24 SHI patients and 25 age- and sex-matched normal controls (NC). Activities of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) were assayed in these patients and controls. The GCS scores of these patients were also recorded for the comparative study.
MATERIALS AND METHODS: Venous blood samples were collected on day 7 (D7) and D21 from SHI patients and NC for the assay of SOD, GR and GSH-Px activities. These changes were correlated with age and changes in GCS scores of patients.
STATISTICAL ANALYSIS: A one-way analysis of variance (ANOVA) was used to compare mean values of each parameter between group 1 (NC), group 2 (D7 changes in SHI patients) and group 3 (D21 changes in SHI patients). ANOVA was followed by Bonferroni post hoc tests. The Pearson correlation was applied to correlate between the antioxidant parameters and age and GCS scores of these patients.
RESULTS: A significant increase in erythrocyte SOD and GSH-Px activities was observed in group 3 as compared to groups 1 and 2. The increase in GSH-Px activity was significant in group 2 as compared to group 1. Although not significant, there was an increase in mean GR activity in groups 2 and 3 as compared to group 1.
CONCLUSION: These findings indicate that SHI patients have shown significantly enhanced erythrocyte SOD and GSH-Px activities during the 21-day posttraumatic study period.

Matched MeSH terms: Glutathione Peroxidase
Time- and dose-related effects of amyloid beta1-40 on retina and optic nerve morphology in rats

Mohd Lazaldin MA, Iezhitsa I, Agarwal R, Bakar NS, Agarwal P, Mohd Ismail N

Int J Neurosci, 2018 Oct;128(10):952-965.
PMID: 29488424 DOI: 10.1080/00207454.2018.1446953

PURPOSE: Amyloid beta (Aβ) is known to contribute to the pathophysiology of retinal neurodegenerative diseases such as glaucoma. Effects of intravitreal Aβ(1-42) on retinal and optic nerve morphology in animal models have widely been studied but not those of Aβ(1-40). Hence, we evaluated the time- and dose-related effects of intravitreal Aβ(1-40) on retinal and optic nerve morphology. Since oxidative stress and brain derived neurotrophic factor (BDNF) are associated with Aβ-induced neuronal damage, we also studied dose and time-related effects of Aβ(1-40) on retinal oxidative stress and BDNF levels.
MATERIALS AND METHODS: Five groups of rats were intravitreally administered with vehicle or Aβ(1-40) in doses of 1.0, 2.5, 5 and 10 nmol. Animals were sacrificed and eyes were enucleated at weeks 1, 2 and 4 post-injection. The retinae were subjected to morphometric analysis and TUNEL staining. Optic nerve sections were stained with toluidine blue and were graded for neurodegenerative effects. The estimation of BDNF and markers of oxidative stress in retina were done using ELISA technique.
RESULTS AND CONCLUSIONS: It was observed that intravitreal Aβ(1-40) causes significant retinal and optic nerve damage up to day 14 post-injection and there was increasing damage with increase in dose. However, on day 30 post-injection both the retinal and optic nerve morphology showed a trend towards normalization. The observations made for retinal cell apoptosis, retinal glutathione, superoxide dismutase activity and BDNF were in accordance with those of morphological changes with deterioration till day 14 and recovery by day 30 post-injection. The findings of this study may provide a guide for selection of appropriate experimental conditions for future studies.

Matched MeSH terms: Glutathione
Fulltext Time and dose-dependent effects of Labisia pumila on bone oxidative status of postmenopausal osteoporosis rat model

Effendy NM, Shuid AN

Nutrients, 2014 Aug;6(8):3288-302.
PMID: 25195641 DOI: 10.3390/nu6083288

Postmenopausal osteoporosis can be associated with oxidative stress and deterioration of antioxidant enzymes. It is mainly treated with estrogen replacement therapy (ERT). Although effective, ERT may cause adverse effects such as breast cancer and pulmonary embolism. Labisia pumila var. alata (LP), a herb used traditionally for women's health was found to protect against estrogen-deficient osteoporosis. An extensive study was conducted in a postmenopausal osteoporosis rat model using several LP doses and duration of treatments to determine if anti-oxidative mechanisms were involved in its bone protective effects. Ninety-six female Sprague-Dawley rats were randomly divided into six groups; baseline group (BL), sham-operated (Sham), ovariectomised control (OVXC), ovariectomised (OVX) and given 64.5 μg/kg of Premarin (ERT), ovariectomised and given 20 mg/kg of LP (LP20) and ovariectomised and given 100 mg/kg of LP (LP100). The groups were further subdivided to receive their respective treatments via daily oral gavages for three, six or nine weeks of treatment periods. Following euthanization, the femora were dissected out for bone oxidative measurements which include superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) levels.

Matched MeSH terms: Glutathione Peroxidase/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; Glutathione Peroxidase/metabolism; Glutathione Reductase/metabolism; Glutathione Transferase/metabolism
Fulltext The therapeutic potential of curcumin in alleviating N-diethylnitrosamine and iron nitrilotriacetate induced renal cell tumours in mice via inhibition of oxidative stress: Implications for cancer chemoprevention

Iqbal M, Shah MD, Vun-Sang S, Okazaki Y, Okada S

Biomed Pharmacother, 2021 Jul;139:111636.
PMID: 33957566 DOI: 10.1016/j.biopha.2021.111636

This study was designed to reveal the protective effects of dietary supplementation of curcumin against renal cell tumours and oxidative stress induced by renal carcinogen iron nitrilotriacetate (Fe-NTA) in ddY male mice. The results showed that mice treated with a renal carcinogen, Fe-NTA, a 35% renal cell tumour incidence was noticed, whereas renal cell tumour occurrence was elevated to 80% in Fe-NTA promoted and N-diethylnitrosamine (DEN)-initiated mice as compared with saline- treated mice. No incidence of tumours has been observed in DEN-initiated non-promoted mice. Diet complemented with 0.5% and 1.0% curcumin fed prior to, during and after treatment with Fe-NTA in DEN-initiated animals, tumour incidence was reduced dose-dependently to about 45% and 30% respectively. Immunohistochemical studies also revealed the increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney tissue of mice treated with an intraperitoneal injection of Fe-NTA (6.0 mg Fe/kg body weight.). Furthermore, Fe-NTA treatment of mice also resulted in significant elevation of malondialdehyde (MDA), serum urea, and creatinine and decreases renal glutathione. However, the changes in most of these parameters were attenuated dose-dependently by prophylactic treatment of animals with 0.5% and 1% curcumin diet, this may be due to its antioxidative impact of curcumin. These results suggest that intake of curcumin is beneficial for the prevention of renal cell tumours and oxidative stress damage mediated by renal carcinogen, Fe-NTA.

Matched MeSH terms: Glutathione
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
The inhibition of human T cell proliferation by the caspase inhibitor z-VAD-FMK is mediated through oxidative stress

Rajah T, Chow SC

Toxicol Appl Pharmacol, 2014 Jul 15;278(2):100-6.
PMID: 24768707 DOI: 10.1016/j.taap.2014.04.014

The caspase inhibitor benzyloxycarbony (Cbz)-l-Val-Ala-Asp (OMe)-fluoromethylketone (z-VAD-FMK) has recently been shown to inhibit T cell proliferation without blocking caspase-8 and caspase-3 activation in primary T cells. We showed in this study that z-VAD-FMK treatment leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in activated T cells. The inhibition of anti-CD3-mediated T cell proliferation induced by z-VAD-FMK was abolished by the presence of low molecular weight thiols such as GSH, N-acetylcysteine (NAC) and l-cysteine, whereas d-cysteine which cannot be metabolised to GSH has no effect. These results suggest that the depletion of intracellular GSH is the underlying cause of z-VAD-FMK-mediated inhibition of T cell activation and proliferation. The presence of exogenous GSH also attenuated the inhibition of anti-CD3-induced CD25 and CD69 expression mediated by z-VAD-FMK. However, none of the low molecular weight thiols were able to restore the caspase-inhibitory properties of z-VAD-FMK in activated T cells where caspase-8 and caspase-3 remain activated and processed into their respective subunits in the presence of the caspase inhibitor. This suggests that the inhibition of T cell proliferation can be uncoupled from the caspase-inhibitory properties of z-VAD-FMK. Taken together, the immunosuppressive effects in primary T cells mediated by z-VAD-FMK are due to oxidative stress via the depletion of GSH.

Matched MeSH terms: Glutathione/metabolism
Fulltext The improvement of the endogenous antioxidant property of stone fish (Actinopyga lecanora) tissue using enzymatic proteolysis

Bordbar S, Ebrahimpour A, Abdul Hamid A, Abdul Manap MY, Anwar F, Saari N

Biomed Res Int, 2013;2013:849529.
PMID: 23586061 DOI: 10.1155/2013/849529

The stone fish (Actinopyga lecanora) ethanolic and methanolic tissue extracts were investigated for total phenolic contents (TPCs) as well as antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH(•)) radical scavenging activity and ferric reducing antioxidant power (FRAP) assays. Both extracts showed low amount of phenolics (20.33 to 17.03 mg of gallic acid equivalents/100 g dried sample) and moderate antioxidant activity (39% to 34% DPPH(•) radical scavenging activity and 23.95 to 22.30 mmol/100 mL FeSO4 FRAP value). Enzymatic proteolysis was carried out in order to improve the antioxidant activity using six commercially available proteases under their optimum conditions. The results revealed that the highest increase in antioxidant activity up to 85% was obtained for papain-generated proteolysate, followed by alcalase (77%), trypsin (75%), pepsin (68%), bromelain (68%), and flavourzyme (50%) as measured by DPPH(•) radical scavenging activity, whilst for the FRAP value, the highest increase in the antioxidant activity up to 39.2 mmol/100 mL FeSO4 was obtained for alcalase-generated proteolysate, followed by papain (29.5 mmol/100 mL FeSO4), trypsin (23.2 mmol/100 mL FeSO4), flavourzyme (24.7 mmol/100 mL FeSO4), bromelain (22.9 mmol/100 mL FeSO4), and pepsin (20.8 mmol/100 mL FeSO4). It is obvious that proteolysis of stone fish tissue by proteolytic enzymes can considerably enhance its antioxidant activity.

Matched MeSH terms: Glutathione/chemistry

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