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.     

Parameters related to oxygen free radicals in erythrocytes,plasma and epidermis of the hairless rat

The following parameters related to oxygen free radicals (OFR) were determined in erythrocytes and the epidermis of hairless rats: catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced (GSH) and oxidized (GSSG) glutathione, glutathione S-transferase (GST), superoxide dismutase (SOD) and thiobarbituric acid reactive substances (TBARS). GSH, GSSG and TBARS were also analyzed in plasma. In erythrocytes, the Pearson correlation coefficients (r) were significant (p < 0.001) between glutathione and other parameters as follows: GSH correlated negatively with GSSG (r = -0.665) and TBARS (r = -0.669); GSSG correlated positively with SOD (r = 0.709) and TBARS (r = 0.752). Plasma GSSG correlated negatively with erythrocytic thermostable GST activity (r = -0.608; p=0.001) and with erythrocytic total GST activity (r = -0.677; p < 0.001). In epidermis (p < 0.001 in all cases), GSH content correlated with GSSG (r = 0.682) and with GPx (r = 0.663); GSSG correlated with GPx (r = 0.731) and with GR (r = 0.794). By multiple linear regression analysis some predictor variables (R(2)) were found: in erythrocytes, thermostable GST was predicted by total GST activity and GSSG, GSSG content was predicted by GSH and by the GSH/GSSG ratio and GPx activity was predicted by GST, CAT and SOD activities; in epidermis, GSSG was predicted by GR and SOD activities and GR was predicted by GSSG, TBARS and GPx. It is concluded that the hairless rat is a good model for studying OFR-related parameters simultaneously in blood and skin, and that it may provide valuable information about other animals under 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.     

Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury

Understanding the molecular pathway(s) of antioxidant gene regulation is of crucial importance for developing antioxidant-inducing agents for the intervention of oxidative cardiac disorders. Accordingly, this study was undertaken to determine the role of Nrf2 signaling in the basal expression as well as the chemical inducibility of endogenous antioxidants and phase 2 enzymes in cardiac fibroblasts. The basal expression of a scope of key cellular antioxidants and phase 2 enzymes was significantly lower in cardiac fibroblasts derived from Nrf2-/- mice than those from wild type control. These include catalase, reduced glutathione (GSH), glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). Incubation of Nrf2+/+ cardiac fibroblasts with 3H-1,2-dithiole-3-thione (D3T) led to a significant induction of superoxide dismutase (SOD), catalase, GSH, GR, glutathione peroxidase (GPx), GST, and NQO1. The inducibility of SOD, catalase, GSH, GR, GST, and NQO1, but not GPx by D3T was completely abolished in Nrf2-/- cells. The Nrf2-/- cardiac fibroblasts were much more sensitive to reactive oxygen and nitrogen species-mediated cytotoxicity. Upregulation of antioxidants and phase 2 enzymes by D3T in Nrf2+/+ cardiac fibroblasts resulted in a dramatically increased resistance to the above species-induced cytotoxicity. In contrast, D3T-treatment of the Nrf2-/- cells only provided a slight cytoprotection. Taken together, this study demonstrates for the first time that Nrf2 is critically involved in the regulation of the basal expression and chemical induction of a number of antioxidants and phase 2 enzymes in cardiac fibroblasts, and is an important factor in controlling cardiac cellular susceptibility to reactive oxygen and nitrogen species-induced cytotoxicity.     

Effect of copper exposure on GST activity and on the expression of four GSTs under oxidative stress condition in the monogonont rotifer, Brachionus koreanus

Glutathione S-transferases (GSTs; EC 2.5.1.18) are major enzymes that function in Phase II detoxification reactions by catalyzing the conjugation of reduced glutathione through cysteine thiol. In this study, we cloned and sequenced four GST genes from the monogonont rotifer Brachionus koreanus. The domain regions of four Bk-GSTs showed a high similarity to those of other species. In addition, to evaluate the potential of GST genes as an early warning signal for oxidative stress, we exposed sublethal concentrations of copper (Cu) to B. koreanus and measured glutathione (GSH) contents and several antioxidant enzymes such as glutathione S-transferase (GST), glutathione peroxidase (GPx; EC 1.11.1.9), and glutathione reductase (GR; EC 1.8.1.7). The reactive oxygen species (ROS) at 12 h and 24 h after copper exposure increased significantly. GSH contents however did not increase significantly and even it decreased at 0.24 mg/L at 12 h. The activities of several antioxidant enzymes, particularly GPx and GR, showed a dramatic increase in 0.24 mg/L of CuCl₂. Messenger RNAs of each Bk-GST showed different patterns of modulations according to GST types, and particularly, Bk-GST-omega, Bk-GST-sigma, and Bk-GST zeta genes were highly sensitive to Cu. These results indicate that Bk-GSTs, functioning as one of the enzymatic defense mechanisms particularly in the early stage of oxidative stress response, were induced by Cu exposure. This also suggests that these genes and related enzymes have a potential as biomarkers for a more sensitive initial stress response.     

The chemical inducibility of mouse cardiac antioxidants and phase 2 enzymes in vivo

The recognition of the critical involvement of oxidative and electrophilic stress in cardiac disorders has led to extensive investigation of the protective effects of exogenous antioxidants on cardiac injury. On the other hand, another strategy for protecting against oxidative/electrophilic cardiac injury may be through induction of the endogenous antioxidants and phase 2 enzymes in myocardium by chemical inducers. However, our understanding of the chemical inducibility of cardiac antioxidants/phase 2 enzymes in vivo is very limited. In addition, careful studies on the basal levels of a scope of endogenous antioxidants/phase 2 enzymes in myocardium as compared with other tissues, such as liver, are lacking. Accordingly, this study was undertaken to determine the basal levels of endogenous antioxidants/phase 2 enzymes, including superoxide dismutase (SOD), catalase, reduced glutathione (GSH), GSH peroxidase (GPx), glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1), and investigate the inducibility of the above antioxidants/phase 2 enzymes by the chemoprotectant, 1,2-dithiole-3-thione (D3T), in cardiac as well as hepatic tissues in C57BL/6 mice. Our results demonstrated that in C57BL/6 mice, the levels of catalase, GSH, GPx, GR, and GST were significantly lower in cardiac tissue than in hepatic tissue. The level of total SOD did not differ significantly between mouse heart and liver. Notably, heart contained a much higher NQO1 activity than liver. Immunoblotting and RT-PCR analyses further demonstrated the high expression of NQO1 protein and mRNA in myocardium. Oral administration of D3T at 0.25 and 0.5 mmol/kg body weight for 3 consecutive days resulted in a significant induction of cardiac SOD, catalase, GR, GST, and NQO1. No significant induction of cardiac GSH and GPx was observed with the above D3T treatment. Only GR, GST, and NQO1 in mouse liver were induced by the D3T treatment. Unexpectedly, we observed a significant D3T dose-dependent decrease in hepatic GPx activity. Taken together, this study demonstrates for the first time that: (1) the expression of NQO1 is remarkably high in mouse myocardium though other cardiac antioxidants/phase 2 enzymes are relatively lower as compared with liver; (2) a number of endogenous antioxidants/phase 2 enzymes in mouse cardiac tissue can be significantly induced by D3T following oral administration; and (3) the inducibility of endogenous antioxidants/phase 2 enzymes by D3T differs between mouse cardiac and hepatic tissues. This study provides a basis for future investigation of the cardioprotection of chemically induced endogenous antioxidants and phase 2 enzymes in myocardium in animal models of oxidative/electrophilic cardiac disorders.     

Alteration in Glutathione Content and Associated Enzyme Activities in the Synaptic Terminals but not in the Non-synaptic Mitochondria from the Frontal Cortex of Parkinson’s Disease Brains

Altered redox dynamics contribute to physiological aging and Parkinson’s disease (PD). This is reflected in the substantia nigra (SN) of PD patients as lowered antioxidant levels and elevated oxidative damage. Contrary to this observation, we previously reported that non-SN regions such as caudate nucleus and frontal cortex (FC) exhibited elevated antioxidants and lowered mitochondrial and oxidative damage indicating constitutive protective mechanisms in PD brains. To investigate whether the sub-cellular distribution of antioxidants could contribute to these protective effects, we examined the distribution of antioxidant/oxidant markers in the neuropil fractions [synaptosomes, non-synaptic mitochondria and cytosol] of FC from PD (n = 9) and controls (n = 8). In the control FC, all the antioxidant activities [Superoxide dismutase (SOD), glutathione (GSH), GSH peroxidase (GPx), GSH-S-transferase (GST)] except glutathione reductase (GR) were the highest in cytosol, but several fold lower in mitochondria and much lower in synaptosomes. However, FC synaptosomes from PD brains had significantly higher levels of GSH (p = 0.01) and related enzymes [GPx (p = 0.02), GR (p = 0.06), GST (p = 0.0001)] compared to controls. Conversely, mitochondria from the FC of PD cases displayed elevated SOD activity (p = 0.02) while the GSH and related enzymes were relatively unaltered. These changes in the neuropil fractions were associated with unchanged or lowered oxidative damage. Further, the mitochondrial content in the synaptosomes of both PD and control brains was ≥five-fold lower compared to the non-synaptic mitochondrial fraction. Altered distribution of oxidant/antioxidant markers in the neuropil fractions of the human brain during aging and PD has implications for (1) degenerative and protective mechanisms (2) distinct antioxidant mechanisms in synaptic terminals compared to other compartments.     

Protective effect of black tea extract on the levels of lipid peroxidation and antioxidant enzymes in liver of mice with pesticide-induced liver injury

Sub-acute hepatotoxicity was induced in mice by exposure to pesticides. The effect of pretreatment with aqueous black tea extract on lipid peroxidation and antioxidants in the liver was investigated. Administering a combination dose of chlorpyriphos and cypermethrin (20 mg kg(-1) each) on alternate days over a 15-day period to male mice resulted in induction of sub-acute toxicity as reflected by elevated levels of liver damage marker enzymes alkaline phosphatase(ALP), aspartate transaminase(AST) and alanine transaminase(ALT). Significantly elevated levels of lipid peroxidation were observed in the experimental group (group III) as compared with control mice. Decreased activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total thiol, glutathione peroxidase (GPx), glutathione reductase(GR) and glutathione-S-transferase (GST) were also observed in pesticide-treated as compared to control mice. Aqueous black tea extract was given as a pretreatment to group IV mice at a dose of 200 mg ml(-1) polyphenols before the pesticide dose, which significantly decreased the levels of lipid peroxidation and significantly elevated the activities of SOD, CAT, GSH, total thiol, GPx, GR and GST in liver to levels similar to the controls. Thus, the data offer support for the claim that the central mechanism of pesticide action occurs via changes in cellular oxidative status and shows conclusively that supplementation with black tea extract protects against the free radical-mediated oxidative stress in hepatocytes of animals with pesticide-induced liver injury.     

Susceptibility to oxidative stress and modulated expression of antioxidant genes in the copper-exposed polychaete Perinereis nuntia

To identify and evaluate potentially useful biomarkers for oxidative stress as early warning indices in the polychaete, Perinereis nuntia, we exposed P. nuntia to copper (Cu) and measured several biomarker enzymes (glutathione S-transferase; GST, glutathione peroxidase; GPx, Metallothionein-like protein; MTLPs, and catalase; CAT) and genes (Pn-GSTs, Pn-CAT, and Pn-MT) with a cellular oxidative index, reactive oxygen species (ROS) level. Accumulated Cu concentrations in P. nuntia increased in a time-dependent manner. Intracellular ROS reached high levels 6h after exposure in P. nuntia with an increase of GST activity and glutathione (GSH) content. Particularly, GSH in polychaetes showed a positive correlation with Cu contents accumulated in P. nuntia. Messenger RNA expressions of GST sigma and GST omega showed relatively high expressions at 50 μg/L of Cu exposure, even though the moderate increase of rest of GST isoforms was also observed. Also regarding long-term exposure, we reared P. nuntia in sediments for 15 days, and found that there was an obvious increase of Pn-GSTs, Pn-CAT, and Pn-MT genes with elevated concentrations of Cu and Cd in polychaete body, compared to initial levels, suggesting that P. nuntia in sediment was affected by metals as well as by other organic pollutants to induce oxidative stress genes and enzymes. These findings suggest that oxidative stress is a potential modulator of defense system of P. nuntia. Several potential biomarker genes are available as early warning signals for environmental biomonitoring.     

Time-dependent oxidative stress caused by benznidazole

Abstract

Benznidazole (BZN) is a nitroimidazole derivative which has a notable trypanocide activity, and it is the only drug used in Brazil and Argentina for the treatment of Chagas' disease. The drug in current use is thought to act, at least in part, by inducing oxidative stress within the parasite. Imidazolic compounds are involved in the production of reactive oxygen species (ROS). In order to evaluate the effect of BZN on ROS production and on the antioxidant status of the host, male rats were treated for different periods of time (2, 4, 6, 10 and 30 days) with 40 mg BZN/kg body weight. After treatment, biomarkers of oxidative stress such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione reductase (GR), and also thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH), total glutathione (TG) and oxidized glutathione (GSSG) concentrations, were measured in crude hepatic homogenates. Our results revealed that BZN is able to cause tissue damage as shown by increased TBARS content, inhibition of some antioxidants and induction of other antioxidants in a concentration- and time-dependent manner. The tissue damage measured as TBARS increased up to the 10th day of treatment. GST activity was inhibited during the BZN treatment. On the other hand, CAT and GR showed similar increased activities at the beginning, followed by decreased activities at the end of the treatment. After 30 days of treatment, GR activity remained low while CAT activity was high, compared to controls. The SOD activities remained unchanged throughout the experimental period. GSH showed lower values at the beginning of BZN treatment but the hepatic concentrations were enhanced at the end of the experimental period. Total glutathione showed a similar profile, and oxidized glutathione showed higher values in rats treated with BZN. In conclusion, these results indicate that, at therapeutic doses, BZN treatment elicits an oxidative stress in rat hepatocytes.     

Systemic oxidative stress in children and teenagers with Down syndrome

Aims

The aim of this study was to evaluate the antioxidant status and oxidative stress biomarkers in the blood of children and teenagers with Down syndrome.

Main methods

The analysis of enzymatic antioxidant defenses, such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST), non-enzymatic antioxidants, such as levels of reduced glutathione (GSH), uric acid (UA) and vitamin E, as well as oxidative damage indicators, such as protein carbonyls (PC) levels and lipoperoxidation (TBARS), of DS individuals (n = 20) compared to healthy controls (n = 18). Except the vitamin E was measured by HPLC, all other markers were measured spectrophotometrically.

Key Findings

Antioxidant enzymes analysis showed significant increases in the SOD (47.2%), CAT (24.7%) and GR (49.6%) activities in DS subjects. No significant difference in GPx activity was detected while GST activity (61.2%) was decreased, and both responses may be consequence of the depletion of GSH (24.9%) levels. There were no significant differences in TBARS levels, while PC levels showed decreased (31.7%) levels compared to healthy controls, which may be related to the increase (16.1%) found in serum UA. Levels of vitamin E showed no significant differences between DS individuals compared to controls.

Significance

The results revealed a systemic pro-oxidant status in DS individuals, evidenced by the increased activity of some important antioxidant enzymes, together with decreased GSH levels in whole blood and elevated UA levels in plasma, probably as an antioxidant compensation related to the redox imbalance in DS individuals.     

Time-dependent oxidative stress caused by benznidazole

Benznidazole (BZN) is a nitroimidazole derivative which has a notable trypanocide activity, and it is the only drug used in Brazil and Argentina for the treatment of Chagas' disease. The drug in current use is thought to act, at least in part, by inducing oxidative stress within the parasite. Imidazolic compounds are involved in the production of reactive oxygen species (ROS). In order to evaluate the effect of BZN on ROS production and on the antioxidant status of the host, male rats were treated for different periods of time (2, 4, 6, 10 and 30 days) with 40 mg BZN/kg body weight. After treatment, biomarkers of oxidative stress such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione reductase (GR), and also thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH), total glutathione (TG) and oxidized glutathione (GSSG) concentrations, were measured in crude hepatic homogenates. Our results revealed that BZN is able to cause tissue damage as shown by increased TBARS content, inhibition of some antioxidants and induction of other antioxidants in a concentration- and time-dependent manner. The tissue damage measured as TBARS increased up to the 10th day of treatment. GST activity was inhibited during the BZN treatment. On the other hand, CAT and GR showed similar increased activities at the beginning, followed by decreased activities at the end of the treatment. After 30 days of treatment, GR activity remained low while CAT activity was high, compared to controls. The SOD activities remained unchanged throughout the experimental period. GSH showed lower values at the beginning of BZN treatment but the hepatic concentrations were enhanced at the end of the experimental period. Total glutathione showed a similar profile, and oxidized glutathione showed higher values in rats treated with BZN. In conclusion, these results indicate that, at therapeutic doses, BZN treatment elicits an oxidative stress in rat hepatocytes.     

Oxidative Stress in the Heart of Rats Infected with Trypanosoma evansi

This study was conducted to investigate the occurrence of oxidative stress in the heart tissue of rats infected with Trypanosoma evansi. Rats were divided into 2 groups (A and B) with 12 animals each, and further subdivided into 4 subgroups (A1 and A2, 6 animals/each; and B1 and B2, 6 animals/each). Animals in the groups B1 and B2 were subcutaneously inoculated with T. evansi. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase activity (SOD), glutathione S-transferase activity (GST), reduced glutathione activity (GSH), and non-protein thiols (NPSH) in the heart tissue were evaluated. At day 5 and 15 post-infection (PI), an increase in the TBARS levels and a decrease in the SOD activity (P<0.05) were observed. GSH and GST activities were decreased in infected animals at day 15 PI (P<0.05). Considering the proper functioning of the heart, it is possible that the changes in the activity of these enzymes involved in the oxidative stress may be related, at least in part, in the pathophysiology of rats infected with T. evansi.     

Oxidative stress in digestive gland and gill of the brown mussel (Perna perna) exposed to air and re-submersed

Mussels Perna perna were exposed to air for 24 h showing a clear increase in the levels of lipid peroxidation and oxidative DNA damage, measured as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo). The levels of lipid peroxidation increased both in the digestive gland and gills, while oxidative DNA damage increased only in the gills. After the 24 h of air exposure, mussels were re-submersed for a period of 3 h, leading values to return to a pre-aerial exposure levels. Control animals were kept immersed during the whole period. Several antioxidant and complementary enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), glutathione S-transferase (GST) and the levels of total glutathione (Total GSH) were assayed in a second set of experiments where one group of mussels were exposed to air for 18 h and other to 1 h re-submersion after 18 h aerial exposure. Only a 52% increase in the glutathione S-transferase activity was observed in the digestive gland, which remained elevated to about 40% after 1 h re-submersion, showing that defense systems can be modulated even during oxygen deprivation in P. perna. The DNA and lipid oxidative damage observed after aerial exposure indicates that mussels face an oxidative challenge, and are able to counteract such an “insult” as values of lipid peroxidation and DNA damage returned to control values after 3 h re-submersion.     

Biochemical markers of oxidative stress in Perna viridis exposed to mercury and temperature

Oxidative damage and antioxidant properties have been studied in Perna viridis subjected to short-term exposure to Hg along with temperature (72h) and long-term temperature exposures (14 days) as pollution biomarkers. The elevated thiobarbituric acid reactive substances (TBA-RS) levels observed in gills and digestive gland under exposure to Hg, individually and combined with temperature, as also long-term temperature stress have been assigned to the oxidative damage resulting in lipid peroxidation (LPX). Increased activities of antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-S-transferase (GST) both in gills and digestive glands under long-term exposures to temperatures are more prominent to heat rather than cold stress suggesting activation of physiological mechanism to scavenge the ROS produced during heat stress. Also decreased values of reduced glutathione (GSH) on long exposures to temperature stress indicate utilisation of this antioxidant, either to scavenge oxiradicals or act in combination with other enzymes, was more than its production capacity under heat stress. The results suggest that temperature variation does alter the active oxygen metabolism by modulating antioxidant enzyme activities, which can be used as biomarker to detect sublethal effects of pollution.     

Vitamins E and C ameliorate the oxidative stresses induced by zinc oxide nanoparticles on liver and gills of Oreochromis niloticus

The current study evaluated the hazards of Zinc oxide nanoparticles (ZnONPs) on Nile Tilapia liver and gill antioxidants enzymes activities and antioxidants genes expressions. The ameliorative action of vitamins E and C mixture was investigated. Two hundred males of Nile Tilapia were exposed to one and two mg?L^?1 of ZnONPs either with or without vitamin C and E mixture for 7 and 15?days. Glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities and gene expression as well glutathione (GSH) and lipid peroxide (LPO) levels were investigated. The results revealed that the exposure to ZnONPs could induce alterations in the liver and gills antioxidants and LPO of Nile Tilapia. Moreover, the mixture of vitamin E and C highly effective in alleviation the toxic effect of ZnONPs.     

Mutated glutathione S-transferase in combination with reduced glutathione shows a synergistic effect in ameliorating oxidative stress and airway inflammation

Oxidative stress is implicated in the pathogenesis of asthma, and antioxidant levels are reduced in asthma patients. Previously, glutathione S-transferase (GST) with reduced IgE binding suppressed oxidative stress and modulated airway inflammation to some extent in mice. GST catalyzes the quenching of reactive oxygen species by reduced glutathione (GSH) and the absence of any one of them may limit antioxidative behavior. This study evaluates the effects of mutated (m) GST with GSH in combination and individually in limiting oxidative stress and inflammatory responses in a mouse model. BALB/c mice were immunized and challenged with ovalbumin. The mice were treated with mGST, GSH, mGST + GSH, or α-lipoic acid by inhalation and sacrificed to evaluate inflammation and oxidative stress parameters. Treatment with the mGST + GSH combination showed significantly reduced total cell (p < 0.01) and eosinophil (p < 0.01) counts in BALF compared to other groups. The lung inflammation score was lowest for the mGST + GSH group, along with reduced IL-4 (p < 0.01) and OVA-specific IgE compared to the other treatment groups. Oxidative stress as per the lipid peroxidation and 8-isoprostane level in BALF of mGST + GSH mice was reduced significantly compared to the individual antioxidants. In conclusion, mGST in combination with GSH has a synergistic effect in reducing airway inflammation compared to the individual antioxidants and has potential for the treatment of asthma.     

Role of antioxidant defense during different stages of preadult life cycle in European corn borer (Ostrinia nubilalis, Hubn.): Diapause and metamorphosis

Antioxidant enzymes, total glutathione (GSH), and ascorbic acid (ASA) were determined in whole body homogenates of nondiapausing larvae, diapausing larvae during the diapausing period (October, December, and February), and in pupae emerged from both diapausing and nondiapausing larvae of the European corn borer (Ostrinia nubilalis, Hubn., Lepidoptera: Pyralidae). The activities of catalase, selenium nondependent glutathione peroxidase (GPx), and glutathione-S-transferase (GST), as well as the content of GSH and ASA, were found to vary throughout the larval diapause. Compared to diapausing larvae, nondiapausing larvae were higher in levels of catalase, GPx, GST, and dehydroascorbate reductase (DHAR) activity. GSH content was also increased. However, nondiapausing larvae contained less ASA than diapausing ones. Pupae had higher GPx and GST activity and an increased ASA content compared to larvae. The pupae emerged from nondiapausing larvae had higher GST, glutathione reductase (GR), and DHAR activities, but lower GPx activity and ASA content than those emerged from diapausing larvae. Correlation analysis revealed differences in the way the antioxidant level is equilibrated for a particular stage and developmental pattern. The results suggest that cellular antioxidants are involved in both the protection of cells and the regulation of redox levels during the pre-adult stages of Ostrinia nubilalis. Arch. Insect Biochem. Physiol. 55:79-89, 2004.     

The use of pentoxifylline as adjuvant therapy with praziquantel downregulates profibrogenic cytokines, collagen deposition and oxidative stress in experimental schistosomiasis mansoni

This study investigates the possible use of pentoxifylline (PTX), with antifibrotic and anti-inflammatory properties, as adjuvant in treatment of schistosomal liver fibrosis through determination of some profibrogenic cytokines, oxidative stress and collagen deposition. Animals were classified into seven groups: normal control (i), Schistosoma mansoni-infected untreated (ii), infected treated with praziquantel (PZQ) curative, 1000 mg/kg (iii) or sub curative, 200 mg/kg dose (iv), infected treated with PTX alone (10 mg/kg/day; 5 days/wk) for 8 weeks starting from the 2nd to the 10th week post infection (v), or in addition to curative (vi) or sub curative dose of PZQ (vii). Serum transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), matrix metalloproteinases-2 (MMP-2) and hepatic hydroxyproline (Hyp) content, glutathione related antioxidant enzymes and malondialdehyde (MDA) were determined. Results showed that S. mansoni infection produced remarkable elevations in the serum levels of TGF-β1, TNF-α, MMP-2 and the hepatic contents of Hyp, glutathione reductase (GR), MDA with significant reduction in reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD) when compared with their corresponding normal controls. Treatment of infected mice with PTX in addition to PZQ curative rather than its sub curative dose produced the best results evidenced by complete normalization in the previously mentioned serum and hepatic parameters. Conclusion: PTX could attenuate liver fibrosis in early stages of S. mansoni infection through downregulation of profibrogenic cytokines, oxidative stress and collagen deposition.