Galangin,a dietary flavonoid,improves antioxidant status and reduces hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats

Objective: To examine the effect of galangin on hyperglycemia-mediated oxidative stress in streptozotocin (STZ)-induced diabetic rats.

Methods: Diabetes was induced by intraperitoneal administration of low-dose STZ (40?mg/kg body weight (BW)) into male albino Wistar rats. Galangin (8?mg/kg BW) or glibenclamide (600?µg/kg BW) was given orally, once daily for 45 days to normal and STZ-induced diabetic rats.

Results: Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes. The levels of insulin and non-enzymatic antioxidants (vitamin C, vitamin E, reduced glutathione) and the activity of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase (GST)) were decreased significantly in diabetic control rats. These altered plasma glucose, insulin, lipid peroxidation products, enzymatic and non-enzymatic antioxidants ions were reverted to near-normal level after the administration of galangin and glibenclamide.

Conclusion: The present study shows that galangin decreased oxidative stress and increased antioxidant status in diabetic rats, which may be due to its antidiabetic and antioxidant potential.     

Prevention of diabetic nephropathy in rats through enhanced renal antioxidative capacity by inhibition of the proteasome

AimsOxidative stress may play an important role in the pathogenesis of diabetic nephropathy (DN). Recent studies have shown that the ubiquitin–proteasome pathway (UPP) and oxidative stress have interaction. We aimed to investigate whether inhibiting the proteasome has a preventive effect on DN through suppression of renal oxidative stress.Main methodsMale Sprague–Dawley rats were randomly divided into three groups: a normal control (NC) group, a streptozotocin-induced DN model group, and a DN plus MG132 (10 μg/kg) treatment group.Key findingsIncreased 24-h urinary protein excretion rate (UPER) and renal pathological changes were all improved after MG132 administration. Furthermore, enhanced renal 26S proteasome activity and concentration in DN rats were effectively reduced after MG132 administration. Increased p47phox and nitrotyrosine (NT) expressions in kidneys of DN rats were decreased after MG132 treatment. Renal mRNA and protein expressions of NF-E2 related factor 2 (Nrf2) were up-regulated by MG132 in comparison to DN alone. Decreased renal mRNA expression of superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione peroxidase (GPx) in DN rats was heightened after MG132 intervention. Depressed activities of renal SOD, CAT and GPx in DN rats were also improved by MG132 treatment. Increased renal nuclear factor κB (NF-κB) activity was inhibited after MG132 administration in DN rats at the end of 12 weeks.SignificanceOur present data suggest that inhibition of the proteasome by low-dose MG132 has a preventive effect on DN development and progression in rats through the up-regulation of antioxidant genes.     

Oxidative Damage Induced by Arsenic in Mice or Rats: A Systematic Review and Meta-Analysis

In this meta-analysis, studies reporting arsenic-induced oxidative damage in mouse models were systematically evaluated to provide a scientific understanding of oxidative stress mechanisms associated with arsenic poisoning. Fifty-eight relevant peer-reviewed publications were identified through exhaustive database searching. Oxidative stress indexes assessed included superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST), glutathione reductase (GR), oxidized glutathione (GSSG), malondialdehyde (MDA), and reactive oxygen species (ROS). Our meta-analysis showed that arsenic exposure generally suppressed measured levels of the antioxidants, SOD, CAT, GSH, GPx, GST, and GR, but increased levels of the oxidants, GSSG, MDA, and ROS. Arsenic valence was important and GR and MDA levels increased to a significantly (P < 0.05) greater extent upon exposure to As³⁺ than to As⁵⁺. Other factors that contributed to a greater overall oxidative effect from arsenic exposure included intervention time, intervention method, dosage, age of animals, and the sample source from which the indexes were estimated. Our meta-analysis effectively summarized a wide range of studies and detected a positive relationship between arsenic exposure and oxidative damage. These data provide a scientific basis for the prevention and treatment of arsenic poisoning.     

Markers of oxidative stress in diabetic mothers and their infants during delivery

Oxidative stress is probably a pathophysiological process leading to disadvantageous outcomes in diabetic pregnancies. We aimed to map a complex of potential markers of oxidative stress in this condition. Diabetic mothers had significantly higher concentrations of thiobarbituric acid reactive substances in the plasma [TBARS] both before (p<0.0001) and after (p<0.001) delivery and also their newborns showed higher values of TBARS (p<0.0001) in comparison with the control group. Diabetic mothers also showed lower concentrations of reduced glutathione in erythrocytes [GSH] both before (p<0.05) and after (p<0.01) delivery and their infants also had lower levels of GSH (p<0.0001). We found a lower total antioxidative capacity of plasma [AOC] before delivery (p<0.05) in the diabetic group in comparison with the control group. Newborns of diabetic mothers had higher plasmatic concentrations of apolipoproteine B [apo B] (p<0.05), higher erythrocyte glutathione peroxidase [GPx] activity (p<0.05) and lower pH (p<0.001) in the umbilical cord blood, when compared with infants of control non-diabetic mothers. We conclude that pregestational and gestational diabetes mellitus represent increased oxidative stress for both mother and her infant. TBARS in plasma are a valuable marker of oxidative stress in this condition. Disruption of glutathione peroxidase/glutathione pattern can be involved in pathophysiology of enhanced oxidative stress in diabetic pregnancies.     

Critical role of exposure time to endogenous oxidative stress in hepatocyte apoptosis

Abstract

We have previously shown that inhibition of catalase and glutathione peroxidase activities in rat primary hepatocytes by 3-amino-1,2,4-triazole (ATZ) and mercaptosuccinic acid (MS) results in sustained oxidative stress, followed by apoptosis. To examine the effects of duration of oxidative stress, ATZ and MS were removed from culture medium at 3, 6 and 9 h after treatment with both inhibitors. Oxidative stress was induced for periods of time by ATZ and MS exposures in primary hepatocytes. Treatment with ATZ and MS reduced catalase (CAT) and glutathione peroxidase (GPx) activities, and decreased CAT and GPx activities recovered to normal values upon withdrawal. Although oxidative stress of up to 6 h duration did not cause cell death, sustained oxidative stress (over 9 h) induced apoptosis. The increase in the glutathione disulfide/reduced glutathione ratio under oxidative stress up to 6 h was transient and reversible, while that due to sustained oxidative stress was irreversible. These results suggest that irreversible redox shifts resulting from sustained oxidative stress play a critical role in the induction of hepatocyte apoptosis in this experimental system.     

Antiperoxidative and antioxidant effects of Casearia esculenta root extract in streptozotocin-induced diabetic rats

Oxidative stress is currently suggested to play as a pathogenesis in the development of diabetes mellitus. The present study was designed to evaluate the effect of Casearia esculenta root extract on oxidative stress-related parameters in streptozotocin (STZ) -induced diabetic rats. Antidiabetic treatment with C. esculenta root extract (45 days) significantly (p < .05) decreased thiobarbituric acid reactive substances (TBARS) and remarkably improved tissue antioxidants status such as glutathione (GSH), ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) in liver and kidney of STZ-diabetic rats. In diabetics rats, the activities of enzymatic antioxidants such as superoxide dismutase (SOD, EC 1.11.1.1) catalase (CAT, EC 1.11.1.6) were decreased significantly while the activity of glutathione peroxidase (GPx, EC 1.11.1.9) decreased in the liver and increased in the kidney. The treatment of diabetic rats with C. esculenta root extract over a 45-day period returned these levels close to normal. These results suggest that C. esculenta root extracts exhibit antiperoxidative as well as antioxidant effects in STZ-induced diabetic rats.     

The quality of the antioxidant defence system in term and preterm twin neonates

Abstract

Objective: Multiple pregnancy is associated with an enhanced metabolism and demand for O2, which may lead to the overproduction of reactive oxygen species and the development of oxidative stress. The degree of oxidative damage depends on the level of the antioxidant protection system of the foetus. The objective of the study was to identify the relationship between the state of the maturity and the antioxidant status of twin neonates. Investigations of the umbilical cord blood were carried out to detect differences in the antioxidant defence system between mature and premature twin neonates.

Methods: The activities of the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes, the levels of reduced glutathione (GSH), protein carbonyls and oxidized lipids and the total antioxidant capacity of the plasma were determined.

Results: The level of lipid peroxidation was significantly higher in the premature neonates. An increase in the total antioxidant capacity was accompanied by a decrease in the damaged protein concentration. Significantly elevated activities of GPx alone were observed in the premature twins, though the GSH content too tended to be increased. The activity of SOD was decreased in the premature neonates.

Discussion: The antioxidant status of twin neonates are mainly influenced by maturity. We suggest that the level of lipid peroxidation might be of clinical value as a marker of pre- and perinatal distress in twins.     

Impact of umbelliferone on erythrocyte redox status in STZ-diabetic rats

Oxidative stress is currently hypothesized to be a mechanism underlying diabetes. The present study was designed to evaluate the effect of umbelliferone (UMB), a derivative of coumarin, on erythrocyte lipid peroxidation, antioxidants, and lipid profile in normal and streptozotocin (STZ) diabetic rats. Diabetes was induced in adult male albino rats of Wistar strain, weighing 180 to 200 g, by the administration of STZ (40 mg/kg/b-wt) intraperitonially. The normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) dissolved in water for 45 days. The diabetic rats had elevated levels of blood glucose and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and lipid hydroperoxide (HP) and decreased levels of nonenzymatic antioxidants (Vitamin C and reduced glutathione [GSH]), elevated levels of vitamin E, and elevated levels of enzymatic antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), elevated glucose-6-phosphate dehydrogenase activity, and altered lipid profile (cholesterol and phospholipids) in erythrocytes. These changes were reversed by treatment with UMB. Thus, our results indicate that the administration of UMB shows promising potential for the restoration of normal blood glucose levels, erythrocyte lipid peroxidation, antioxidants, and lipid profile in STZ-diabetic.     

Hypertension aggravates glomerular dysfunction with oxidative stress in a rat model of diabetic nephropathy

Oxidative stress may contribute to the pathogenesis of diabetic nephropathy (DN), although the detailed mechanism of reactive oxygen species (ROS) regulation is still unclear. This study examined the effect of high-salt diet on ROS production and expression of antioxidant enzymes in control and experimentally diabetic rats. Wistar fatty rats (WFR) as a type 2 diabetes mellitus model and Wistar lean rats (WLR) as a control were fed a normal-salt diet (NS) and high-salt diet (HS) from the age of 6 to 14 weeks. We then examined the blood pressure, urinary albumin excretion (UAE), and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. The expression of antioxidant enzymes including α-catalase (CAT), Cu-Zn superoxide dismutase (SOD), Mn SOD, and glutathione peroxidase (GPx) were analyzed in the glomeruli of the rats using Western blotting. The expression of NAD(P)H oxidase p47^phox and NFκB p65 was evaluated using immunohistochemical staining. By 14 weeks of age, the WFR-HS group exhibited hypertension and markedly increased UAE. The level of 8-OHdG, a marker of oxidative damage, in the WFR-HS group was also higher than that in the WLR groups or WFR-NS group. The expression of α-CAT and Mn SOD proteins was significantly decreased in isolated glomeruli in the WFR-HS group. GPx and Cu-Zn SOD expression did not differ between the WFR and WLR groups. High expression of ROS and decreases in antioxidants were seen in the glomeruli of diabetic rats with hypertension, suggesting that oxidative stress may be involved in the development of DN.     

Attenuation of N-methyl-N'-nitro-N-nitrosoguanidine induced genotoxicity and oxidative stress by tomato and garlic combination

The protective effect of pretreatment with tomato and garlic against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced genotoxicity and oxidative stress was investigated in male Swiss mice. In vivo bone marrow micronucleus test was performed to assess the antigenotoxic effect of tomato and garlic. Oxidative stress was monitored by estimating the extent of lipid peroxidation and the status of the glutathione redox cycle antioxidants. Increased frequency of bone marrow micronuclei with enhanced lipid peroxidation was associated with compromised antioxidant defenses in MNNG treated animals. Although pretreatment with tomato and garlic significantly reduced the frequencies of MNNG-induced bone marrow micronuclei, the combination of tomato and garlic exerted a greater protective effect. This was associated with modulation of lipid peroxidation as well as reduced glutathione (GSH) and the GSH-dependent enzymes glutathione peroxidase (GPx) and glutathione-S-transferase (GST). These findings suggest that a diet containing even low levels of different naturally occurring compounds is effective in exerting antigenotoxic effects by modulating oxidative stress.     

Lead-induced oxidative damage in rats/mice: A meta-analysis

BackgroundLead (Pb) is ubiquitous in the environment and is an environmental genotoxic metal. Pb accumulation in the body could cause the oxidative stress.ObjectiveThis meta-analysis aimed to perform a systematic evaluation of the extent of oxidative damage in rats/mice induced by lead.MethodsAll relevant articles in English or Chinese were retrieved from Embase, PubMed, Web of Science, Medline, China National Knowledge Infrastructure, and Chinese Biological Medicine databases from their inception date until July 22, 2018.ResultsA total of 108 eligible articles were included in this study. The indicators of oxidative stress included malondialdehyde (MDA), glutathione disulfide (GSSG), reactive oxygen species (ROS), hydrogen peroxide (H₂O₂), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione-s-transferase (GST). The meta-analysis showed that lead significantly increased oxidants levels, such as MDA, GSSG, ROS, and H₂O₂ (P < 0.05), and significantly reduced the level of antioxidants, such as CAT, GPx, GR, GSH, SOD, and GST (P < 0.05). The intraperitoneal mode was more effective than water drinking mode in reducing the levels of CAT, GPx, GSH, and SOD (P < 0.05). Other factors that influenced the overall oxidative stress, including species of animals, type of tissues, and intervention dosage and time, were comprehensively evaluated.ConclusionThe results of meta-analysis indicated that mice were more sensitive to lead than rats, and intraperitoneal mode was an effective intervention mean. High doses and long periods of lead treatment can cause serious oxidative damage. Moreover, testicular was more vulnerable to lead than other tissues. These results provided scientific evidence for preventing and treating lead toxicity.     

Influence of treatment of diabetic rats with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid on parameters of oxidative stress

Treatment with antioxidants may act more effectively to alter markers of free radical damage in combinations than singly. This study has determined whether treatment with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid was more effective at reducing oxidative stress in diabetic rats than treatment with these antioxidants alone. It is not feasible, based on this study, to assume that there are interactive effects that make combinations of these antioxidants more effective than any one alone to combat oxidative stress. Female Sprague-Dawley rats, normal and streptozotocin-induced diabetic, were treated (10 mg/kg/day ip for 14 days) with pycnogenol, beta-carotene, pycnogenol + beta-carotene, or pycnogenol + beta-carotene + alpha-lipoic acid; controls were untreated. Concentrations of thiobarbituric acid reactive substances, glutathione and glutathione disulfide, and activities of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase were measured in liver, kidney, and heart. Four types of effects were observed: (1) treatment with beta-carotene alone either reversed (cardiac glutathione disulfide) or elevated (cardiac glutathione, hepatic glutathione peroxidase activity) levels seen in diabetic animals; (2) beta-carotene alone produced no effect, but pycnogenol both alone and in combinations elevated (renal glutathione peroxidase and glutathione reductase activities, hepatic glutathione reductase activity and glutathione disulfide) or depressed (cardiac glutathione disulfide) levels seen in untreated diabetic animals; (3) all treatments with antioxidants, either alone or in combination, either normalized (lipid peroxidation in all tissues), elevated (hepatic GSH, cardiac glutathione peroxidase activity), or had no effect on (activities of hepatic catalase and superoxide dismutase in all tissues) levels seen in diabetic animals; (4) in only one case (cardiac glutathione reductase activity) levels in diabetic animals treated with combinations of antioxidants were normal, but elevated in animals treated with either antioxidant alone. Antioxidant effects seem to be dependent on the nature of the antioxidant used and not on combination effects.     

Effects of new antioxidant compounds PNU-104067F and PNU-74389G on antioxidant defense in normal and diabetic rats

Diabetes mellitus and its complications are associated with elevated oxidative stress, leading to much interest in antioxidant compounds as possible therapeutic agents. Two new classes of antioxidant compounds, the pyrrolopyrimidines and the 21-aminosteroids, are known to inhibit lipid peroxidation and other biomolecular oxidation. We hypothesized that in the presence of excess oxidants or the impaired antioxidant defense seen in diabetes mellitus, administration of antioxidants such as these may reverse the effects of diabetes on antioxidant parameters. This study measured the effects of subchronic (14 day) treatment with a pyrrolopyrimidine (PNU-104067F) or a 21-aminosteroid (PNU-74389G) in normal and diabetic Sprague-Dawley rats. Activity levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, concentrations of oxidized and reduced glutathione, and lipid peroxidation were used as measures of antioxidant defense in liver, kidney, heart, and brain tissue. In normal rats, the only effect was a 43% increase in cardiac lipid peroxidation after treatment with PNU-104067F. In diabetic rats, the only reversals of the effects of diabetes were a 30% decrease in hepatic glutathione peroxidase activity after PNU-74389G treatment and a 33% increase in cardiac glutathione disulfide concentration after PNU-104067F treatment. In contrast to these effects, increased cardiac glutathione peroxidase and catalase activities, increased brain glutathione peroxidase activity, increased hepatic lipid peroxidation, decreased hepatic glutathione content, and decreased hepatic catalase activity were seen in diabetic rats, reflecting an exacerbation of the effects of diabetes.     

Protective effect of green tea extract against the erythrocytic oxidative stress injury during Mycobacterium tuberculosis infection in mice

The present study has been undertaken to monitor the extent of oxidative stress in mice infected with M. tuberculosis and the role of crude green tea extract in repairing the oxidative damage. The mice were divided into three groups of 9 each; normal, infected-untreated and infected-treated. The infected group of animals exhibited significant enhancement of erythrocytic catalase and glutathione peroxidase activities along with elevated levels of erythrocytic total thiols and plasma lipid peroxidation as compared to normal animals. The infected group also exhibited significantly decreased activity of superoxide dismutase and levels of glutathione in erythrocytes. Upon oral administration of green tea extract for seven days the oxidative stress parameters were reverted back to near normal levels as evidenced by a fall in catalase, glutathione peroxidase, total thiol and extent of lipid peroxidation with concomitant increase in the levels of SOD and reduced glutathione in infected animals. The findings thus, portray that there is a high oxidative stress during early stages of tuberculosis and antioxidants such as green tea extract, can play a vital role by reducing stress through adjuvant therapy.     

Insulin resistance and not steatosis is associated with modifications in oxidative stress markers in chronic hepatitis C,non-3 genotype

Abstract

Background: Modifications of oxidative stress are reported in hepatitis C. The relationship between insulin resistance (IR), steatosis and oxidative stress is not established. Materials and methods: One hundred and eighty-seven HCV-RNA patients were assessed by determination of biochemical, metabolic and viral features, HOMA-IR and morphological alterations. In the 52-non-3 genotypes sub-group and 35 healthy individuals, thiobarbituric acid (TBARS), total glutathione (total-GSH), vitamins C and E, lycopene, β-carotene, glutathione peroxidase (GPx), catalase and superoxide dismutase were determined. Results: In non-3 genotype patients, steatosis was associated with higher values of BMI, HOMA-IR and triglycerides. In the 52-HCV sub-group, values of TBARS, GPx and total-GSH differ from the control group. Despite these, differences could not be observed according to the presence of steatosis, patients with IR presented significant differences regarding total-GSH (p=0.019), β-carotene (p=0.006), lycopene (p=0.005) and GPx (p=0.009). Conclusion: In non-3 genotype HCV carries, IR, and not steatosis, is associated with modifications in serum levels of oxidative stress.     

Neuroprotective effect of carvedilol and melatonin on 3-nitropropionic acid-induced neurotoxicity in neuroblastoma

In neurodegenerative diseases, progressive oxidative stress is a major event that precedes neuronal death. Oxidative stress is characterized by an imbalance between oxidants and antioxidants. This imbalance induced oxidative molecular and cell damage, reducing cellular viability. 3-Nitropropionic acid (3NP) causes oxidative stress and other molecular and cellular changes similar to those observed in neurons of patients with Huntington’s disease. Since carvedilol and melatonin act as free-radical scavengers, this study examined the effect of carvedilol (10^?5 M) and melatonin (10^?5 M) on oxidative and cell damage induced by 3NP in N1E-115 neuroblastoma cells. Carvedilol and melatonin prevented the increases in lipid peroxidation and total LDH activity, as well as the depletion of reduced glutathione (GSH) and the reduction of antioxidative enzymes activities in N1E-115 cells incubated with 100 mM 3NP. All these carvedilol and melatonin effects were more intense when the drugs were added before rather than after inducing the damage by 3NP. These results also provided evidence supporting the hypothesis that carvedilol and melatonin can be useful for treating neurodegenerative diseases, such as Huntington’s disease.     

Impact of d-pinitol on the attenuation of proinflammatory cytokines,hyperglycemia-mediated oxidative stress and protection of kidney tissue ultrastructure in streptozotocin-induced diabetic rats

Oxidative stress plays a crucial role in the progression and development of diabetes and its complications due to chronic hyperglycemia. The present study was aimed to investigate the kidney tissue protective nature of d-pinitol, a cyclitol present in soybean, by assessing the key markers of hyperglycemia-mediated oxidative stress, proinflammatory cytokines and ultrastructural alterations in streptozotocin-induced diabetic rats. Oral administration of d-pinitol (50 mg/kg body weight/day) for 30 days to diabetic group of rats showed a significant elevation in the level of total protein and significant decline in the levels of blood urea, serum uric acid, creatinine and advanced glycation endproducts (AGEs) and kidney proinflammatory cytokines such as TNF-α, IL-1β, IL-6, NF-κB p65 subunit and nitrite. Further, d-pinitol administration elicited a significant attenuation in the activities of kidney enzymatic antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and the levels of kidney non-enzymatic antioxidants such as vitamin E, vitamin C and reduced glutathione (GSH) in the diabetic group of rats, with a concomitant decline in the levels of kidney lipid peroxides, hydroperoxides and protein carbonyls. The histological and ultrastructural observations on the kidney tissues also confirmed the renoprotective nature of d-pinitol. Thus the present study demonstrated the renoprotective nature of d-pinitol by attenuating the hyperglycemia-mediated proinflammatory cytokines and antioxidant competence in kidney tissues of streptozotocin-induced diabetic rats.     

Effect of zinc and paraquat co-exposure on neurodegeneration: Modulation of oxidative stress and expression of metallothioneins,toxicant responsive and transporter genes in rats

Abstract

Oxidative stress is implicated in Parkinson's disease (PD). Metallothioneins (MT), cytochrome P450 IIE1 (CYP2E1) and glutathione S-transferases alpha4-4 (GSTA4-4) are involved in oxidative stress-mediated damage. Altered dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) are also documented in PD. The present study was undertaken to investigate the effect of Zn and PQ co-exposure on neurodegeneration in rats. A significant reduction was observed in spontaneous locomotor activity (SLA), striatal dopamine (DA) levels, tyrosine hydroxylase (TH) immunoreactivity, glutathione reductase (GR) and catalase activity along with increased lipid peroxidation (LPO) and glutathione peroxidase (GPx) activity after Zn and/or PQ exposure. Zn and/or PQ exposure increased gene expression of DAT, CYP2E1, GSTA4-4, MT-I and MT-II, but reduced the expression of VMAT-2. Protein expression analysis of TH, VMAT-2 and DAT showed results similar to those obtained with gene expression study. Zn and PQ co-exposure caused a more pronounced effect than that of individual exposure. The results obtained in this study suggest that, similar to PQ, Zn induced neurodegeneration via alterations in oxidative stress and expression of the above-mentioned genes. However, the effect of Zn+PQ was only slightly higher than that of alone, indicating that probably Zn and PQ follow some different molecular events leading to neurodegeneration.     

Protective effect of 4,4′-diaminodiphenylsulphone against oxidative stress but not to apoptotic stress in human diploid fibroblasts

Abstract

The antibiotic drug 4,4′-diaminodiphenylsulphone (DDS) is used to treat several dermatologic diseases, including Hansen's disease. This study confirmed the antioxidant nature of DDS in hydrogen peroxide (H₂O₂)-induced oxidative stress and assessed its role in other apoptotic stresses in human diploid fibroblasts (HDFs). Oxidative stress was effectively reduced by DDS in a dose-dependent manner. Moreover, the oxidative stress-induced increases in the levels of the p53 and p21 proteins were inhibited by pre-treatment with DDS. In addition, H₂O₂ and DDS increased the level of cytochrome P450 (CYP450) IIE1 in HDFs, implicating a role for DDS in H₂O₂ scavenging via the activation of CYP450. DDS treatment increased the activity of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the GSH/GSSG ratio, indicating activation of the glutathione system against oxidative stress. However, DDS showed no protective effects on HDFs against other apoptotic stimuli, such as thapsigargin and staurosporine, suggesting that DDS would act only against oxidative stress. Therefore, in addition to its antibiotic function, DDS is a potent antioxidant against H₂O₂-induced oxidative stress in HDFs.     

Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum

Oxidative stress is a hypothesis for the association of reactive oxygen species with cerebrovascular and neurodegenerative diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the cerebellum of rats. Thirty-two adult male Sprague–Dawley rats were divided into four equal groups (control, ethanol, betaine, and betaine plus ethanol) with different dietary regimens and were followed up for 1 month. Total homocysteine (tHcy) of plasma and cerebellum homogenate was determined by an Axis^® homocysteine EIA kit, and antioxidant enzyme (glutathione peroxidase (GPx), SOD, and CAT) activities of cerebellum homogenate were measured chemically by a spectrophotometer. Lipid peroxidation of cerebellum was shown by the measurement of thiobarbituric reactive substances (TBARS) via a spectrophotometer. Ethanol-induced hyperhomocysteinemia was manifested by an increase in the concentrations of tHcy in the plasma and cerebellum homogenates of the ethanol group, while ethanol-induced oxidative stress was indicated via an increase in lipid peroxidation marker (TBARS) in cerebellum homogenates of ethanol-treated rats. In contrast, betaine prevented hyperhomocysteinemia and oxidative stress in the betaine plus ethanol group as well as the betaine group. The results of the present investigation indicated that the protective effect of betaine is probably related to its ability to strengthen the cerebellum membrane cells by enhancement of antioxidant enzyme activity principally GPx, while the methyl donor effect of betaine to reduce hyperhomocysteinemia has been explained previously and confirmed in the present study.