GSH) Level And Glutathione Peroxidase Research Articles

The Protective Effect of Sonneratia apetala Fruit Extract on Acetaminophen-Induced Liver Injury in Mice.

Acute liver injury is a common consequence of taking overdose of acetaminophen (APAP). The aim of this study was to evaluate the antioxidant activity and hepatoprotective effect of a mangrove plant Sonneratia apetala fruit extract (SAFE) on APAP-induced liver injury in mice. Mice were orally pretreated with SAFE (100, 200, and 400 mg/kg) daily for one week. The control and APAP groups were intragastrically administered with distilled water, and NAC group was treated with N-Acetyl-L-cysteine (NAC) before APAP exposure. The results manifested that SAFE significantly improved survival rates, attenuated hepatic histological damage, and decreased the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum in APAP-exposed mice. SAFE treatment also increased glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity, enhanced catalase (CAT), and total antioxidant capacity (T-AOC), as well as reducing malondialdehyde (MDA) level in liver. In addition, the formation of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and elevation of myeloperoxidase (MPO) in APAP-exposed mice were inhibited after SAFE treatment. And SAFE also displayed high DPPH radical scavenging activity and reducing power in vitro. The main bioactive components of SAFE such as total phenol, flavonoid, condensed tannin, and carbohydrate were determined. The current study proved that SAFE exerted potential protective effect against APAP-induced acute liver injury, which might be associated with the antioxidant and anti-inflammatory activities of SAFE.

Modulator role of infliximab and methotrexate through the transient receptor potential melastatin 2 (TRPM2) channel in neutrophils of patients with rheumatoid arthritis: a pilot study.

IntroductionRheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease causing symmetric polyarthritis. In this study, we aimed to investigate the effects of infliximab (INF) and methotrexate (MTX) on apoptosis, oxidative stress, and calcium signaling in the neutrophils of RA patients.Material and methodsNeutrophils were isolated from 10 patients with newly diagnosed RA and 10 healthy controls. They were divided into four groups (control, RA, RA + MTX, RA + INF) and incubated with MTX and INF. In the cell viability (MTT) test, the ideal non-toxic dose and incubation time of MTX were found to be 0.1 mM and 1 h, respectively. The neutrophils were also incubated with the TRPM2 channel blocker N-(p-amylcinnamoyl) anthranilic acid (ACA).ResultsIntracellular free Ca2+ concentration, intracellular reactive oxygen species (ROS) production, mitochondrial depolarization, lipid peroxidation, apoptosis, and caspase 3 and caspase 9 activities were found to be significantly higher in the neutrophils of RA patients compared to controls. MTT, reduced glutathione (GSH) level, and glutathione peroxidase (GSHPx) activity were significantly lower in the neutrophils of RA patients. However, MTT, GSH and GSHPx values were detected to be significantly increased with INF and MTX therapies. The Ca2+ concentrations were further decreased by the ACA therapy.ConclusionsOur results suggest that INF and MTX are useful antagonists in apoptosis and mitochondrial oxidative stress in the neutrophils of RA patients. INF and MTX decreased the Ca2+ concentration through inhibition of the TRPM2 channel in the neutrophils of RA patients. It may be a new pathway in the mechanisms of anti-rheumatic drugs.

Protective effect of Hesperidin and Tiger nut against Acrylamide toxicity in female rats

Phytochemicals that have antioxidant effect play important role in protection against several diseases in humans. This study was carried out to evaluate the efficacy of hesperidin and tiger nut against the early changes that may be related to the toxicity of acrylamide in female rats. 72 Sprague Dawley female rats were divided into six groups (12 rat/group): control group (I); hesperidin (HES) treated group (II); tiger nut (TN) treated group (III); Acrylamide (ACR) treated group (IV); HES-ACR treated group (V); and TN-ACR treated group (VI). There was a significant increase in the levels of serum carcino embryonic antigen (CEA), malondialdehyde (MDA), protein carbonyls (CO), ALT, AST, LDH, urea and creatinine while no significant changes of serum total sialic acid, progesterone (prog) and estradiol (E2) levels, and significant decreases of body weights, catalase (Cat) activity, superoxide dismutase (SOD) activity, reduced glutathione (GSH) level, and glutathione peroxidase (GSH-Px) activity of ACR treated group compared with the control. Our results suggested that supplementation of a diet with hesperidin provided antioxidant defense more significant than tiger nut against the toxicity of ACR in breast, liver and kidney tissues.

Role of oxidative stress and inducible nitric oxide synthase in morphine-induced tolerance and dependence in mice. Effect of alpha-lipoic acid

In this study, the possible role of oxidative stress and nitric oxide (NO) synthase isoforms in the development of morphine tolerance and dependence, and effect of alpha-lipoic acid on these parameters were investigated in mice. The development of morphine tolerance as measured by the hot plate test and dependence, as assessed by naloxone-precipitated withdrawal manifestations, produced an increase in brain glutamate and malondialdehyde (MDA) levels and NO production as well as a decrease in brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity. Also, the development of these syndromes increased inducible but not neuronal NO synthase mRNA and protein expressions in mice brain. Co-administration of alpha-lipoic acid (α-LA) inhibited the development of morphine tolerance and dependence, their associated biochemical alterations, except elevation of brain glutamate level, and their associated increase in brain inducible NO synthase mRNA and protein expressions. The inhibitory effect of α-LA on morphine-induced tolerance and dependence and on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent administration of the NMDA receptor antagonist, dizocilpine, the antioxidant, N-acetylcysteine or the selective inducible NO synthase inhibitor, aminoguanidine. On the other hand, this inhibitory effect of α-LA was not changed by concurrent administration of the selective neuronal NO synthase inhibitor, 7-nitroindazole but antagonized by concurrent administration of the NO precursor, l-arginine. These results suggest that α-LA through inhibition of morphine-induced oxidative stress and increase in the expression and activity of inducible NO synthase in the brain can attenuate the development of morphine tolerance and dependence.

Inhibition of brain oxidative stress and inducible nitric oxide synthase expression by thymoquinone attenuates the development of morphine tolerance and dependence in mice

In this study, the effect of thymoquinone on morphine-induced tolerance and dependence in mice was investigated. Repeated administration of thymoquinone along with morphine attenuated the development of morphine tolerance, as measured by the hot plate test, and dependence, as assessed by naloxone-precipitated withdrawal manifestations. Concurrently, morphine-induced progressive increase in brain malondialdehyde (MDA) level and nitric oxide (NO) production as well as progressive decrease in brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity were inhibited by co-administration of thymoquinone. Morphine-induced progressive increase in brain glutamate level was not inhibited by concomitant administration of thymoquinone. Similarly, co-administration of thymoquinone inhibited naloxone-induced increase in brain MDA level, NO overproduction and decrease in brain intracellular GSH level and GSH-Px activities but it did not inhibit naloxone-induced elevation of brain glutamate level in morphine-dependent mice. The inhibitory effect of thymoquinone on morphine-induced tolerance and dependence on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine, the antioxidant, N-acetylcysteine or the NO synthase inhibitor, L-N (G)-nitroarginine methyl ester. On the other hand, this inhibitory effect of thymoquinone was antagonized by concurrent i.p. administration of NO precursor, l-arginine. In addition, concomitant administration of thymoquinone inhibited morphine tolerance and dependence-induced increase in inducible but not in neuronal NO synthase mRNA expression in mice brain. These results demonstrate that inhibition of morphine-induced oxidative stress, increase in the expression of brain inducible NO synthase and NO overproduction by thymoquinone can attenuate the development of morphine tolerance and dependence.

Acute phase response and oxidative stress status in familial Mediterranean fever (FMF)

We aimed to determine acute phase response (APR) and oxidative stress in patients with familial Mediterranean fever (FMF) and compare these characteristics with those in healthy controls; 20 patients with FMF and 15 healthy controls were enrolled in the study. The erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), fibrinogen, and leukocyte levels were determined as markers of APR. Thiobarbituric acid reactive substances (TBARS), conjugated diene, and lipid hydroperoxide levels were measured as markers of lipid peroxidation. Carbonyl group and thiol (T-SH) levels were analyzed to determine the oxidative damage to proteins, and 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to reflect DNA oxidation. The erythrocyte glutathione (GSH) level, and glutathione peroxidase (GSH-Px), CuZn superoxide dismutase (CuZn SOD), and catalase activities were measured as markers of antioxidant status. Conjugated diene (p < 0.001) and carbonyl group (p < 0.05) levels were significantly higher and GSH-Px activity (p < 0.01) was significantly lower in FMF patients compared with controls. FMF patients in the attack period (n = 8) had significantly higher CRP, ESR, fibrinogen, and leukocyte levels (p < 0.001) than patients in the attack-free period (n = 12). The T-SH level (p < 0.05) was significantly higher and CuZn SOD activity was significantly lower (p < 0.05) in FMF patients in the attack period. The findings revealed upregulated APR during the attack period in FMF patients and enhanced oxidative stress in the FMF patients as compared to controls.

Involvement of glutamate, oxidative stress and inducible nitric oxide synthase in the convulsant activity of ciprofloxacin in mice

This study investigated the potential convulsive activity of ciprofloxacin in mice and the possible mechanism(s) of this activity. Intraperitoneal (i.p.) administration of ciprofloxacin into mice resulted in convulsive seizures in a dose-dependent manner. The clonic median convulsant dose (CD50) of ciprofloxacin in mice was increased by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine, not changed by pretreatment with 7-nitroindazole and decreased by pretreatment with l-arginine and fenbufen. The increase in nitric oxide (NO) production and malondialdehyde (MDA) level as well as the decrease in intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity induced by the estimated clonic CD50 of ciprofloxacin in mice brain was inhibited by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine. These biochemical alterations were not changed by pretreatment with 7-nitroindazole but enhanced by pretreatment with l-arginine. The elevation induced by the clonic CD50 of ciprofloxacin in brain glutamate level was not changed by pretreatment with MK-801, alpha-lipoic acid, aminoguanidine or l-arginine. Combined treatment of mice with fenbufen and ciprofloxacin produced elevation of brain NO production and glutamate and MDA levels as well as inhibition of brain intracellular GSH level and GSH-Px activity. In addition, i.p. administration of the clonic CD50 of ciprofloxacin produced an increase in inducible but not in neuronal NO synthase mRNA and protein expressions in mice brain. These results suggest that elevation of brain glutamate levels with consequent oxidative stress and increase in the expression and activity of brain inducible NO synthase may play a pivotal role in ciprofloxacin-induced convulsive seizures.

Acute phase response and oxidative stress status in familial Mediterranean fever (FMF)

We aimed to determine acute phase response (APR) and oxidative stress in patients with familial Mediterranean fever (FMF) and compare these characteristics with those in healthy controls; 20 patients with FMF and 15 healthy controls were enrolled in the study. The erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), fibrinogen, and leukocyte levels were determined as markers of APR. Thiobarbituric acid reactive substances (TBARS), conjugated diene, and lipid hydroperoxide levels were measured as markers of lipid peroxidation. Carbonyl group and thiol (T-SH) levels were analyzed to determine the oxidative damage to proteins, and 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to reflect DNA oxidation. The erythrocyte glutathione (GSH) level, and glutathione peroxidase (GSH-Px), CuZn superoxide dismutase (CuZn SOD), and catalase activities were measured as markers of antioxidant status. Conjugated diene (p < 0.001) and carbonyl group (p < 0.05) levels were significantly higher and GSH-Px activity (p < 0.01) was significantly lower in FMF patients compared with controls. FMF patients in the attack period (n = 8) had significantly higher CRP, ESR, fibrinogen, and leukocyte levels (p < 0.001) than patients in the attack-free period (n = 12). The T-SH level (p < 0.05) was significantly higher and CuZn SOD activity was significantly lower (p < 0.05) in FMF patients in the attack period. The findings revealed upregulated APR during the attack period in FMF patients and enhanced oxidative stress in the FMF patients as compared to controls.

Effect of Pregnancy and Foetal Number on Diameter of Corpus Luteum, Maternal Progesterone Concentration and Oxidant/Antioxidant Balance in Ewes

The aim of this study was to determine the changes in diameter of corpus luteum (CL), maternal progesterone (P) concentration, lipid peroxidation and non-enzymatic antioxidant levels along with enzymatic antioxidant activities in pregnant ewes bearing single and twin foetuses. The ewes were selected from healthy animals that were brought to the abattoir for slaughtering. The ewes were divided into three groups: Group 1 (non-pregnant, non-oestrous, n = 30), Group 2 (pregnant bearing a single foetus, n = 30) and Group 3 (pregnant bearing twin foetuses, n = 12) after they were slaughtered. Pregnant ewes were in the first half of the pregnancy. The diameter of CL and P concentration of pregnant ewes bearing a single foetus or twin foetuses were found higher than that found in non-pregnant ewes. Similarly, the P concentration of pregnant ewes bearing twin foetuses was higher than that found in pregnant ewes bearing a single foetus. Malondialdehyde (MDA) level in pregnant ewes bearing twin foetuses was higher than that found in both non-pregnant and pregnant ewes bearing a single foetus. The serum glutathione (GSH) level and glutathione-peroxidase (GSH-Px) activity of pregnant ewes bearing twin foetuses were found lower than that found in non-pregnant ewes. Additionally, the GSH-Px activity of pregnant ewes bearing twin foetuses was found lower than that found in pregnant ewes bearing a single foetus. No significant difference was found between pregnant ewes bearing female and male foetus with respect to diameter of CL, P concentration and oxidative stress parameters. There were significant positive correlations between foetal number (0, 1, 2) and diameter of CL, P concentration, MDA level, and between P concentration and diameter of CL, MDA level. However, significant negative correlations were found between foetal number (0, 1, 2) and GSH level, GSH-Px activity, and between P concentration and GSH-Px activity. In conclusion, the diameter of CL enlarges, P production increases and oxidant/antioxidant balance impairs because of the gestation stress in ewes during pregnancy.

Alpha-lipoic acid protects against potassium cyanide-induced seizures and mortality

This study was proposed to investigate the potential protective effect of alpha-lipoic acid (α-LA) against potassium cyanide (KCN)-induced seizures and lethality in mice. The intraperitoneal ED 50 value of KCN, as measured by induction of clonic and tonic seizures was increased by pretreatment of mice with α-LA (25, 50 and 100 mg/kg) intraperitoneally in a dose-dependent manner. Similarly, the intraperitoneal LD 50 value of KCN, based on 24 h mortality, was increased by pretreatment with α-LA in a dose-dependent manner. Intraperitoneal injection of the estimated ED 50 of KCN (4.8 mg/kg) into mice increased, 1 h later, nitric oxide (NO) production and brain glutamate and malondialdehyde (MDA) levels. The estimated ED 50 of KCN also decreased brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity in these animals. Administration of the estimated LD 50 of KCN (6 mg/kg) produced, 24 h later, similar marked biochemical alterations in surviving animals. Pretreatment of mice with α-LA inhibited; dose-dependently KCN (ED 50 and LD 50)-induced an increase in NO production and brain MDA level as well as a decrease in brain intracellular GSH level and GSH-Px activity. The elevation induced by KCN in brain glutamate level was not inhibited by α-LA. It can be concluded that the protective effect of α-LA against KCN-induced seizures and lethality may be due to inhibition of NO overproduction and maintenance of intracellular antioxidant defense mechanisms.

Oxidative stress and thyroid hormones in patients with liver diseases

Background The liver metabolizes the thyroid hormones and regulates their systemic endocrine effects so liver disease could affect thyroid hormone metabolism. Oxidative stress could play a role in the pathogenesis and progression of liver diseases. The objective of this study was to investigate serum levels of oxidative stress and antioxidant in liver diseases as prognostic markers and know the importance of these antioxidants level in relation to thyroid hormones. Methods Serum nitric oxide (NO), malondialdehyde (MDA) and triiodothyronine (T 3), thyroxine (T 4), thyroid stimulating hormone (TSH), apolipoprotein-1 (APOA1) levels and erythrocyte reduced glutathione (GSH) level and glutathione peroxidase (GSHPx) and glutathione reductase (GR) activities were determined in 20 control subjects, 13 patients with non-alcoholic steatohepatitis (NASH), 18 patients with chronic HCV, 17 patients with compensated cirrhotic HCV and 42 patients with decompensated cirrhotic HCV. Results Cirrhotic patients with HCV had higher NO and MDA levels while lower T 3 and erythrocyte GSH levels, and GSHPx activity than the chronic. Serum T 3 showed negative correlation with serum NO and MDA whereas positive correlation with APOA1, GSH, and GSHPx in cirrhotic patients with HCV. Conclusion The measurement of the total T 3, NO, MDA, GSH reduced and GSHPx as biomarkers for liver diseases might be a beneficial tool, helping in monitoring the state of liver disease patients.

Caffeic acid phenethyl ester prevents ovary ischemia/reperfusion injury in rabbits

Protective effect of caffeic acid phenethyl ester (CAPE) on ovary ischemia/reperfusion (IR) injury was investigated in this study. Twenty four New Zealand rabbits were divided into 4 groups as follows: group S served as sham. Group C was intraperitoneally injected with CAPE (8.5 mg/kg). In groups E + IR and C + IR, 1% ethanol and CAPE was given intraperitoneally before torsion, respectively. Then, the ovaries were subjected to IR in both groups. Ovary reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity in group E + IR were significantly reduced compared to that of group S. GSH level and GSH-Px activity was significantly increased in group C + I/R. Thiobarbituric acid reactive substances (TBARS) and catalase (CAT) activity in group E + I/R was significantly higher than in group S. CAT activity was decreased to normal levels by CAPE treatment in group C + I/R, while TBARS in group C + IR was significantly reduced compared to that of E + IR. According to histopathological examination, severe congestion, hemorrhage, edema and leukocyte infiltration were observed in E + I/R group. CAPE prominently reduced degenerative effects of IR injury thus it alleviates free radical damage. In conclusion, CAPE which is able to prevent IR-induced injury in the ovaries may be of therapeutic value before the surgical correction.

Alpha- Lipoic Acid Protects against Potassium Cyanide-Induced Seizures and Mortality

This study was proposed to investigate the potential protective effect of alpha-lipoic acid ( α -LA) against potassium cyanide (KCN) -induced seizures and lethality in mice. The intraperitoneal ED50 value of KCN, as measured by induction of clonic and tonic seizures was increased by pretreatment of mice with α -LA (25, 50 and 100 mg/kg) intraperitoneally in a dose-dependent manner. Similarly, the intraperitoneal LD50 value of KCN, based on 24 h mortality, was increased by pretreatment with α -LA in a dose -dependent manner. Intraperitoneal injection of the estimated ED50 of KCN (4.8 mg/kg) increased, 1h later, nitric oxide (NO) production and brain glutamate and lipid peroxidation levels and reduced intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity in mice showing convulsions. Also, administration of the estimated LD50 of KCN (6 mg/kg) produced, 24 h later, similar marked changes in these parameters in surviving animals. Pretreatment of mice with α -LA inhibited, dose- dependently KCN (ED50 and LD50 ) - induced an increase in NO production and lipid peroxidation level as well as a decrease in intracellular GSH level and GSH-Px activity. It can be concluded that the protective effect of α -LA against KCN - induced seizures and lethality may be due to inhibition of NO overproduction and maintenance of intracellular antioxidant defense mechanisms.

Effect of anti-oxidants and oxidative stress parameters on ram semen after the freeze–thawing process

Oxidative damage to sperm resulting from reactive oxygen species generated by the cellular components of semen is one of the main causes for the decline in motility and fertility of sperm during the freeze–thawing process. The aim of this study was thus to determine the effects of anti-oxidants on standard semen parameters, lipid peroxidation (LPO) and anti-oxidant activities after the freeze–thawing of ram semen. Ejaculates collected from four Akkaraman rams, were pooled and evaluated at 33 °C. Semen samples were diluted in a Tris-based extender containing the anti-oxidants glutathione (GSH) (5 mM), oxidized glutathione (GSSG) (5 mM) or cysteine (5 mM) and an extender containing no anti-oxidants (control), cooled to 5 °C and frozen in 0.25 ml French straws. Frozen straws were thawed individually for 20 s in a water bath (37 °C) for microscopic evaluation. The use of an extender supplemented with cysteine led to the highest ( P < 0.01) post-thaw motility (61.0 ± 1.9%), compared to the other treatment groups. No significant differences were observed in viability, acrosome damage and total abnormalities, and following the hypo-osmotic swelling test (HOST), following supplementation with anti-oxidants after the thawing of the semen. Following the thawing process, the levels of malondialdehyde (MDA) did not change with the addition of anti-oxidants, compared to the control. The GSH level and glutathione peroxidase (GSH-PX) activity remained significantly higher upon the addition of GSH (3.33 ± 0.14 nmol/ml and 22.02 ± 1.27 IU/g protein) and GSSG (3.24 ± 0.08 nmol/ml and 20.17 ± 3.38 IU/g protein) compared to the other treatment ( P < 0.001) groups. Only cysteine significantly elevated the activity of catalase (CAT, 842.40 ± 90.42 kU/l) following the freeze–thawing process. The Vitamin E (VitE) level was significantly higher, when compared to GSSG, cysteine and the control, when GSH (4.21 ± 0.20 mg/dl) was added to the freezing extender ( P < 0.001). It could be concluded that future efforts aimed on improving the efficiency of cryopreservation of ram sperm should concentrate on the use of anti-oxidant additives. The results obtained provide a new approach to the cryopreservation of ram semen, and could positively contribute to intensive sheep production.

The effects of hormone replacement therapy on lipid peroxidation and antioxidant status

Objective: A number of studies have consistently shown a lower cardiovascular risk in women who received postmenopausal hormone replacement therapy (HRT). The aim of our study was to examine the effects of HRT on lipid peroxidation and antioxidant status, which were likely to be involved in the pathophysiology of atherosclerosis. Methods: We measured erythrocyte and plasma thiobarbituric acid reactive substances (TBARS) levels as expression of lipid peroxidation-end product malondialdehyde, and also erythrocyte reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity as indicators of the antioxidant status of the 35 postmenopausal women with HRT (mean age: 51.81±4.57 yr; body mass index (BMI): 26.56±3.78 kg/m 2) and 35 postmenopausal women without HRT (mean age: 47.50±3.64; BMI: 27.42±3.43 kg/m 2). Results: In the group with HRT, erythrocyte and plasma TBARS levels were significantly lower than in the group without HRT ( P<0.003 and P<0.001, respectively). Erythrocyte GSH level and GSH-Px activity was found to be increased significantly in the group with HRT in comparison with the group without HRT ( P<0.001 and P<0.001, respectively). There was not any correlation between the erythrocyte and plasma TBARS and erythrocyte GSH levels and GSH-Px activity with duration of HRT (mean 3.5±1.3 yr). Conclusion: Our results show that HRT is beneficial in the protection against oxidative damage and can prevent atherosclerotic complications.