Dietary intake of inorganic mercury: bioaccumulation and oxidative stress parameters in the neotropical fish Hoplias malabaricus

This study evaluated the effects of trophic and subchronic exposure to inorganic mercury (Hg) on the oxidative stress biomarkers and its bioaccumulation potential in the liver, gills, white muscle and heart of the freshwater top predator fish, Hoplias malabaricus, fed with contaminated live juveniles of matrinxã, Brycon amazonicus, as prey vehicle. Inorganic mercury increased superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase, and glutathione reductase (GR) activities in the liver, white muscle and heart. Gills CAT activity remained unchanged while GPx and GR values showed a significant decrease. In the liver and gills, Hg induced significant increase in the reduced (GSH) and oxidized (GSSG) glutathione content, concomitantly with a significant decrease in [GSH]/[GSSG] ratio. Differently, in cardiac tissue, the Hg caused an increase in GSH level and increase in [GSH]/[GSSG] ratio. Lipid and protein oxidation and metallothionein levels were significantly higher after Hg trophic exposure in the liver, gills and heart, but remained at control values in the white muscle. Tissue-specific responses against oxidative stress were observed, and the liver and gills were the most sensitive organs, showing signs of redox homeostasis failure. At the end of the experiment, dietary inorganic mercury accumulated through food chain levels. In order, Hg bioaccumulation was: gills > liver ? white muscle = heart. These results pointed out the potential of inorganic Hg to bioaccumulate in aquatic systems. Taken together, our findings suggest that Hg, even in the inorganic form and sublethal amounts, is a risk factor for aquatic biota.     

Inorganic mercury exposure: toxicological effects,oxidative stress biomarkers and bioaccumulation in the tropical freshwater fish matrinxã, <Emphasis Type="Italic">Brycon amazonicus</Emphasis> (Spix and Agassiz, 1829)

Alterations in the antioxidant cellular system have often been proposed as biomarkers of pollutant-mediated toxicity. This study evaluated the effects of mercury on oxidative stress biomarkers and bioaccumulation in the liver, gills, white muscle and heart of the freshwater fish matrinxã, Brycon amazonicus, exposed to a nominal and sub-lethal concentration (~20% of 96 h-LC₅₀) of 0.15 mg L^?1 of mercury chloride (HgCl₂) for 96 h in a static system. Increases in superoxide dismutase, catalase, glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) were observed in all tissues after HgCl₂ exposure, except for white muscle GR activity and hepatic GPx. In the liver and gills, the exposure to HgCl₂ also induced significant increases in reduced glutathione (GSH). Conversely, exposure to HgCl₂ caused a significant decrease in the GSH levels and an increase in the oxidized glutathione (GSSG) content in the white muscle, while both GSH and GSSG levels increased significantly in the heart muscle. Metallothionein concentrations were significantly high after HgCl₂ exposure in the liver, gills and heart, but remained at control values in the white muscle. HgCl₂ exposure induced oxidative damage, increasing the lipid peroxidation and protein carbonyl content in all tissues. Mercury accumulated significantly in all the fish tissue. The pattern of accumulation follows the order gills > liver ? heart > white muscle. In conclusion, these data suggest that oxidative stress in response to inorganic mercury exposure could be the main pathway of toxicity induced by this metal in fish.     

Effects of di(2‐ethylhexyl)phthalate on testicular oxidant/antioxidant status in selenium‐deficient and selenium‐supplemented rats

Di(ethylhexyl)phthalate (DEHP), the most widely used plasticizer, was investigated to determine whether an oxidative stress process was one of the underlying mechanisms for its testicular toxicity potential. To evaluate the effects of selenium (Se), status on the toxicity of DEHP was further objective of this study, as Se is known to play a critical role in testis and in the modulation of intracellular redox equilibrium. Se deficiency was produced in 3‐weeks‐old Sprague–Dawley rats feeding them ≤0.05 mg Se /kg diet for 5 weeks, and Se‐supplementation group was on 1 mg Se/kg diet. DEHP‐treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S‐transferase (GST); concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and thus the GSH/GSSG redox ratio; and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP was found to induce oxidative stress in rat testis, as evidenced by significant decrease in GSH/GSSG redox ratio (>10‐fold) and marked increase in TBARS levels, and its effects were more pronounced in Se‐deficient rats with ～18.5‐fold decrease in GSH/GSSG redox ratio and a significant decrease in GPx4 activity, whereas Se supplementation was protective by providing substantial elevation of redox ratio and reducing the lipid peroxidation. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting testicular tissue from the oxidant stressor activity of DEHP. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 98–107, 2014.     

Comparison of the effect of chronic cadmium exposure on the antioxidant defense systems of kidney and brain in rat

Abstract

Cadmium (Cd²⁺) produces toxic effects on various tissues as kidney and liver, so several studies have focused to explore the effect produced by different doses and exposure times of this metal. However, little has been reported about the effect that Cd²⁺ shows in the brain in vivo. Hence, this study aimed at comparing the effect of chronic Cd²⁺ exposure on antioxidant defense systems of kidney and brain in rats. Six groups of male rats were employed; five were administered for 45 days with different doses of cadmium chloride (0.187, 0.375, 0.562, 0.937 and 1.125?mg/kg; i.p.) and the other was used as control. Free radicals (FRs) were directly quantified by electron paramagnetic resonance (EPR) spectroscopy; malondialdehyde (MDA), reduced glutathione (GSH) and the activity expression of superoxide dismutase (SOD2) and catalase (CAT) were also measured. The EPR results showed that there was no increase in FR content in kidney or brain. MDA and GSH levels increased in kidney but not in the brain. The SOD2 activity was not altered, but its expression decreased in both tissues. On the other hand, CAT activity and expression tended to increase at low doses and decrease at high doses in both tissues. Therefore, these results suggest that there exist compensatory mechanisms in both kidney and brain that are capable of avoiding the toxic effects exerted by Cd²⁺ at these doses and exposure time.     

Occupational airborne contamination in South Brazil: 2. Oxidative stress detected in the blood of workers of incineration of hospital residues

One of the most useful methods for elimination of solid residues of health services (SRHS) is incineration. However, it also provokes the emission of several hazardous air pollutants such as heavy metals, furans and dioxins, which produce reactive oxygen species and oxidative stress. The present study, which is parallel to an accompanied paper (Ávila Jr. et al., this issue), investigated several enzymatic and non-enzymatic biomarkers of oxidative stress in the blood (contents of vitamin E, lipoperoxidation = TBARS, reduced glutathione = GSH, oxidized glutathione = GSSG, and activities of glutathione S-transferase = GST, glutathione reductase = GR, glutathione peroxidase = GPx, catalase = CAT and superoxide dismutase = SOD), in three different groups (n = 20 each) exposed to airborne contamination associated with incineration of SRHS: workers directly (ca. 100 m from the incinerator) and indirectly exposed (residents living ca. 5 km the incineration site), and controls (non-exposed subjects). TBARS and GSSG levels were increased whilst GSH, TG and α-tocopherol contents were decreased in workers and residents compared to controls. Increased GST and CAT activities and decreased GPx activities were detected in exposed subjects compared to controls, while GR did not show any difference among the groups. In conclusion, subjects directly or indirectly exposed to SRHS are facing an oxidative insult and health risk regarding fly ashes contamination from SRHS incineration.     

Influence of iron on modulation of the antioxidant system in rat brains exposed to lead

The objective of this study was to evaluate markers of oxidative stress in the brains of rats exposed to lead acetate (Pb(C₂H₃O₂)₂), either associated or not associated with ferrous sulfate (FeSO₄). A total of 36 weaning rats (Rattus norvegicus) were divided into 6 groups of six animals and exposed to lead acetate for six weeks. In the control group (control), the animals received deionized water. The Pb260 and Pb260 + Fe received 260 µM lead acetate, and the Pb1050 and Pb1050 + Fe received 1050 µM lead acetate. The Pb260 + Fe and Pb1050 + Fe were supplemented with 20 mg of ferrous sulfate/Kg body weight every 2 days. Group Fe received deionized water and ferrous sulfate. The rat brains were collected to analyze the enzymatic activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the concentration of reduced glutathione (GSH), lipid peroxidation (TBARS), and total antioxidant substance (TAS) (DPPH^? technique). The activity of SOD and GPx in the experimental groups decreased compared to the control, together with the concentration of GSH (p < 0.05). For CAT analysis, SOD tended to increase in concentration in the experimental groups without a concomitant exposure to FeSO₄, whereas GPx showed a slight tendency to increase in activity compared to the control. For TAS‐DPPH^?, there was a decrease in the experimental groups (p < 0.05). According to the results, SOD, GPx, and GSH were affected by lead acetate and exposure to ferrous sulfate changed this dynamic. However, further studies are needed to verify whether ferrous sulfate acts as a protectant against the toxic effects of lead. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 813–822, 2017.     

Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats

Abstract

The major side effect of gentamicin (GEN) is nephrotoxicity which in turn restricts the clinical use of this drug. In this study, the effect of gallic acid (GA) on gentamicin-induced nephrotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups: control, GEN (100 mg/kg/day), GEN + GA (30 mg/kg/day), GA (30 mg/kg/day). All drug administrations were done intraperitoneally (i.p) for eight consecutive days. Twenty-four hours after the last administration, blood samples were collected to determine serum creatinine (Cr), blood urea nitrogen (BUN). The right kidney was used for histological examination. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity were assayed in left renal tissue. Results showed a significant increase in the levels of MDA, NO, Cr, and BUN and decrease of GSH, CAT, GPx, and SOD by GEN administration. Co-administration with GA showed reduction in the levels of MDA, NO, Cr, and BUN and increase in GSH, CAT, GPx, and SOD. Also, the nephroprotective effect of GA was confirmed by the histological examination of the kidneys. The results of our study showed that GA exerts a significant nephroprotective effect against GEN-induced nephrotoxicity.     

Pro/antioxidant status in young healthy women using oral contraceptives

The aim of the study was to analyze the effects of oral contraceptives (OCs) on pro/antioxidant status in the blood of healthy women aged 20–25 years.Individuals were divided into OCs users and OCs nonusers. Markers of oxidative stress in the blood such as Cu, Cu/Zn ratio, malondialdehyde (MDA), glutathione oxidized (GSSG), and gamma-glutamyl transpeptidase (GGT) were determined. Antioxidants such as glutathione reduced (GSH), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione S-transferase (GST), and superoxide dismutase (SOD) were estimated.Higher Cu concentrations, Cu/Zn ratio and GGT activity in women taking OCs were noted. A significant increase in MDA concentrations in oral OCs users was observed. Heightened activity of CAT in plasma was observed in OCs users, whereas SOD activity remained unchanged in plasma and erythrocyte lysate. A decline of GSH and GSSG in whole blood and glutathiono-dependent enzymes (GPx in plasma, GR in plasma and GST in lysate) was shown.Use of OCs leads to a pro/antioxidant imbalance. The results in the present study confirmed that GGT is an early marker of oxidative stress. Catalase is the main antioxidant, involved in the removal of free radicals in OCs users.     

Modifications on Antioxidant Capacity and Lipid Peroxidation in Mice under Fraxetin Treatment

Fraxetin belongs to an extensive group of natural phenolic antioxidants. We have investigated the modifications in endogenous antioxidant capacity; superoxide dismutase (SOD), catalase (CAT), total and selenium-dependent glutathione peroxidases (GPx) and glutathione reductase (GR) and stress index; glutathione disulphide (GSSG)/reduced glutathione (GSH) ratio and thiobarbituric acid-reactive substances (TBARs) in liver and brain supernatants of C57BL/6J male 12-month-old mice under fraxetin treatment for 30 days. Liver SOD and GPx (total and Se-dependent) activities were not significantly affected by fraxetin, whereas they were increased in the brain compared with control animals. GR activity increased significantly only in the liver of treated mice. Fraxetin treatment-related decreases were shown for GSSG/GSH ratio and rate of accumulation of TBARs (not significant in TBARs) in both tissues. We concluded that the net effect of fraxetin treatment on endogenous antioxidant capacity suggests that this compound might provide an important resistance to, or protection against, free-radical-mediated events which contribute to degenerative diseases of ageing.     

Oxidative damage effects in the copepod Tigriopus japonicus Mori experimentally exposed to nickel

Tigriopus japonicus Mori has been recognized as a good model for toxicological testing of marine pollutants. Recently, a large number of genes have been identified from this copepod, and their mRNA expression has been studied independently against exposure to marine pollutants; however, biochemical-response information is relatively scarce. The response of T. japonicus to nickel (Ni) additions was examined under laboratory-controlled conditions in 12 days exposure. Superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), acetylcholinesterase (AchE), reduced glutathione (GSH), the ratio of reduced to oxidized glutathione (GSH/GSSG) and metallothionein (MT) were analyzed for Ni treatments (0, 0.125, 0.25, 0.75 and 3.0 mg/L) after 1, 4, 7 and 12 days. The thiobarbituric reactive species assay was used to evaluate lipid peroxidation (LPO) level in copepods after exposure. The results showed that Ni remarkably affected the biochemical parameters (SOD, GPx, GST, GSH, and GSH/GSSG) after certain exposure durations. However, the copepod’s LPO level was significantly decreased under metal treatments after exposure, hinting that the factors involved in LPO might not significantly depend on the operations and functions in the antioxidant system. Ni exhibited the neurotoxicity to copepods, because its use obviously elevated AchE activity. During exposure, Ni initially displayed an inhibition effect but induced MT synthesis in T. japonicus by day 12, probably being responsible for metal detoxification. Thus, Ni had intervened in the detoxification process and antioxidant system of this copepod, and it could be used as a suitable bioindicator of Ni exposure via measuring SOD, GPx, GST, and MT as biomarkers.     

EGCG inhibits Cd2+-induced apoptosis through scavenging ROS rather than chelating Cd2+ in HL-7702 cells

Context and objective: Epigallocatechin-3-gallat (EGCG), the major catechin in green tea, shows a potential protective effect against heavy metal toxicity to humans. Apoptosis is one of the key events in cadmium (Cd²⁺)-induced cytotoxicity. Nevertheless, the study of EGCG on Cd²⁺-induced apoptosis is rarely reported. The objective of this study was to clarify the effect and detailed mechanism of EGCG on Cd²⁺-induced apoptosis.

Methods: Normal human liver cells (HL-7702) were treated with Cd²⁺ for 21?h, and then co-treated with EGCG for 3?h. Cell viability, apoptosis, intracellular reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (MMP) and caspase-3 activity were detected. On the other hand, the chelation of Cd²⁺ with EGCG was tested by UV-Vis spectroscopy analysis and Nuclear Magnetic Resonance (¹H NMR) spectroscopy under neutral condition (pH 7.2).

Results and conclusion: Cd²⁺ significantly decreased the cell viability and induced apoptosis in HL-7702 cells. Conversely, EGCG co-treatment resulted in significant inhibition of Cd²⁺-induced reduction of cell viability and apoptosis, implying a rescue effect of EGCG against Cd²⁺ poisoning. The protective effect most likely arises from scavenging ROS and maintaining redox homeostasis, as the generation of intracellular ROS and MDA is significantly reduced by EGCG, which further prevents MMP collapse and suppresses caspase-3 activity. However, no evidence is observed for the chelation of EGCG with Cd²⁺ under neutral condition. Therefore, a clear conclusion from this work can be made that EGCG could inhibit Cd²⁺-induced apoptosis by acting as a ROS scavenger rather than a metal chelating agent.     

Yellow eel (Anguilla anguilla) development in NW Portuguese estuaries with different contamination levels

The aims of the present study were to compare the health status of yellow eels (Anguilla anguilla) developing in three estuaries of the NW Portuguese coast with different levels of pollution and their physiological responses to combined effects of environmental variation and pollution. For this, a field study was performed using a multi-parameter approach, including eels condition indexes and biomarkers, water quality variables and other environmental factors. Sixteen biological parameters were assessed, namely: hepatosomatic index (LSI), Fulton’s condition index (K), lipid peroxidation (LPO), total glutathione (TG), reduced glutathione (GSH), oxidised glutathione (GSSG), GSH/GSSG, and the activity of the enzymes acetylcholinesterase (AChE), lactate dehydrogenase (LDH), sodium-potassium ATPase (Na⁺/K⁺-ATPase), ethoxyresorufin O-deethylase (EROD), glutathione S-transferases (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR). Ten environmental factors were also measured in water: temperature, salinity, pH, phosphates, nitrates, nitrites, ammonium, silica, phenol and hardness. Globally, the biomarkers indicate exposure and toxic effects of pollutants on eels living in contaminated estuaries. The relationships between biological and environmental variables were assessed through redundancy analysis. K and LSI indexes, AChE and Na⁺/K⁺-ATPase, total glutathione levels and the antioxidant enzymes CAT, GR, and SOD where the factors most discriminating reference (Minho River estuary) from contaminated estuaries (Lima and Douro Rivers estuaries). Moreover, the most striking outcomes of pollutants exposure on biological responses were observed during winter, probably due to a joint effect of cold weather and pollution stress. Altogether, the results indicate that the development of eels in the polluted estuaries of Lima and Douro rivers is interfering with physiological functions determinant for their survival and performance. This may increase the mortality rates during the continental life-phase of the species and decrease the percentage of animals able to successfully complete their oceanic migration and, thus, reduce the contribution of each generation to the next one.     

Glutathione redox status of control and cadmium oxide-exposed rat lungs during oxidant stress

Activities of enzymes responsible for the maintenance of reduced glutathione (GSH) levels have been shown in a previous study to be increased in rat lungs following a 3-h exposure to cadmium oxide aerosols at 5.0 mg/m3. In this study, the ability of the lung to maintain levels of GSH during challenge with tert-butyl hydroperoxide (tBuOOH) was evaluated in isolated perfused lungs from control and cadmium oxide-exposed rats. Changes in glutathione redox status were indicated by measurements of nonprotein sulfhydryls (NPSH), total glutathione (1/2 GSH + GSSG), and glutathione disulfide (GSSG) in liquid nitrogen freeze-clamped lungs after 3-min infusions with 0-0.6 mM tBuOOH. In control and cadmium oxide-exposed lungs, levels of 1/2 GSH + GSSG remained constant over the range of 0-0.6 mM tBuOOH, indicating that no loss of glutathione from the system had occurred. In experiments with control lungs, levels of NPSH fell from 8.04 +/- 0.22 to 3.09 +/- 0.40 mumol/g dry weight when tBuOOH concentrations were increased from 0 to 0.6 mM (n = 20-23). In cadmium oxide-exposed lungs, NPSH levels also decreased proportionally to increases in GSSG. However, at concentrations of 0.075 and 0.15 mM tBuOOH, significantly smaller decreases in NPSH levels were observed in cadmium oxide-exposed lungs compared with controls. This protection against the GSH-depleting effects of tBuOOH might be explained by increased tissue levels of GSH-related enzymes.     

Comparative study of natural antioxidants - curcumin, resveratrol and melatonin - in cadmium-induced oxidative damage in mice

The present study was designed to examine the antioxidative effect of curcumin, resveratrol and melatonin pre-treatment on cadmium-induced oxidative damage and cadmium distribution in an experimental model in mice. Male CD mice were treated once daily for 3 days with curcumin (50mg/kg b.w., p.o.), resveratrol (20mg/kg b.w., p.o.) or melatonin (12mg/kg, p.o.), dispersed in 0.5% methylcellulose. One hour after the last dose of antioxidants cadmium chloride was administered (7mg/kg b.w., s.c.) to pre-treated animals and control animals receiving methylcellulose. At 24th h after Cd administration the lipid peroxidation (LP - expressed as malondialdehyde production), reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx) were estimated in liver homogenates. Cadmium concentration was measured in the liver, kidneys, testes and brain by AAS. Cadmium chloride administration to mice induced hepatic lipid peroxidation (to 133%, p<0.001), decreased GSH content (to 65%, p<0.001) and inhibited catalase (to 68%, p<0.001) and GPx activity (to 60%, p<0.001) in the liver. Curcumin, resveratrol and melatonin oral pre-treatment completely prevented the Cd-induced lipid peroxidation and Cd-induced inhibition of GPx hepatic activity. Resveratrol was effective against Cd-induced inhibition of catalase activity (p<0.001). The decrease in hepatic GSH level was not prevented by curcumin, resveratrol or melatonin pre-treatment. In mice treated with antioxidants alone the level of LP, GSH, GPx or CAT was not different from control levels. The pre-treatment with antioxidants did not affect cadmium distribution in the tissues of Cd-intoxicated mice. The results demonstrate that curcumin, resveratrol and melatonin pre-treatment effectively protect against cadmium-induced lipid peroxidation and ameliorate the adverse effect of cadmium on antioxidant status without any reduction in tissue Cd burden.     

Caffeic acid phenethyl ester protects against tamoxifen-induced hepatotoxicity in rats

Tamoxifen (TAM) is widely used in the treatment and prevention of breast cancer. Adverse effects of TAM include hepatotoxicity. Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been used in folk medicine for diverse ailments. In the current study, the protective effects of CAPE against TAM-induced hepatotoxicity in female rats were evaluated. TAM (45 mg/kg/day, i.p., for 10 consecutive days) resulted in an elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), depletion of liver reduced glutathione (GSH) and accumulation of oxidized glutathione (GSSG) and lipid peroxidation (LPO). Also, TAM treatment resulted in inhibition of hepatic activity of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT). Further, it raised liver tumor necrosis factor-alpha (TNF-α) level and induced histopathological changes. Pretreatment with CAPE (2.84 mg/kg/day; i.p., for 20 consecutive days, starting 10 days before TAM injection) significantly prevented the elevation in serum activity of the assessed enzymes. CAPE significantly inhibited TAM-induced hepatic GSH depletion and GSSG and LPO accumulation. Consistently, CAPE normalized the activity of GR, GPx, SOD and CAT, inhibited the rise in TNF-α and ameliorated the histopathological changes. In conclusion, CAPE protects against TAM-induced hepatotoxicity.     

Roles of Glutathione in Antioxidant Defense,Inflammation, and Neuron Differentiation in the Thalamus of HIV-1 Transgenic Rats

Inflammation and oxidative stress in the brain are major causes of HIV-associated neurocognitive disorders. Previously we have reported high content of glutathione (GSH) in the thalamus of rats with F344 genetic background. In this study, we investigated the changes of GSH metabolism and GSH-dependent antioxidant enzymes in the rat thalamus in response to HIV-1 transgenesis, and their associations with oxidative stress, inflammation, and neuronal development. Male HIV-1 transgenic (HIV-1Tg) rats and wild type F344 rats at 10 months were used in this study, with 5 rats in each group. Parameters measured in this study included: total and oxidized GSH, glutathione peroxidase (GPx), glutathione-S-transferase (GST), gamma-glutamylcysteine synthetase (GCS), gamma-glutamyl transferase (GGT), cysteine/cystine transporters, 4-hydroxynonenal (HNE), interleukin 12 (IL12), neuronal nuclei (NeuN), microtubule-associated protein (MAP2), and glia fibrillary acidic protein (GFAP). The levels of total GSH, oxidized GSH (GSSG) and MAP2 protein, and enzymatic activities of GCS, GPx and GST were significantly higher in HIV-1Tg rats compared with F344 rats, but the ratio of GSSG/GSH, activity of GGT and levels of HNE, NeuN protein and GFAP protein did not change. HIV-1Tg rats showed a lower level of IL12 protein. GSH positively correlated with GCS, GST and MAP2, GSSG/GSH ratio positively correlated with HNE and IL12, the activities of GPx, GST and GCS positively correlated with each other, and negatively correlated with HNE. These findings suggest an important role of the GSH-centered system in reducing oxidative stress and neuroinflammation, and enhancing neuron differentiation in the thalamus of HIV-1Tg rats.     

Changes in antioxidant defense systems induced by thiram in V79 Chinese hamster fibroblasts.

The role of antioxidant defence systems in protection against oxidative damage of lipids and proteins induced by fungicide thiram during in vitro exposure was investigated in cultured Chinese hamster V79 cells with normal, depleted, and elevated glutathione (GSH) levels. We analyzed the catalytic activities of superoxide dismutases (SOD1 and SOD2), Se-dependent and Se-independent glutathione peroxidases (GSH-Px), glutathione reductase (GR), and catalase (CAT), as well as total glutathione/glutathione disulfide ratio (GSH(total)/GSSG). Thiram treatment resulted in an increase in activities of SOD1, Se-dependent GSH-Px, and GR at the highest tested dose (150 microM). On the contrary, inhibition of CAT and Se-independent GSH-Px activities, and no significant changes in the level of SOD2 activity was observed at any tested doses (100-150 microM). GSH(total)/GSSG ratio in the 100 microM thiram treated cells was not significantly changed comparing to the control, despite significant decrease of GSH total (50%). In 150 microM thiram treated cells the ratio falls to 43% of control value. Pretreatment with l-buthionine sulfoximine (L-BSO), an inhibitor of GSH synthesis, significantly enhanced decrease in CAT and Se-independent GSH-Px activities, as well as GSH(total)/GSSG ratio, and reduced Se-dependent GSH-Px activity, following exposure to thiram. Simultaneously, L-BSO pretreatment enhanced increase in SOD1 activity, and had no effect on SOD2, following thiram exposure. Pretreatment with N-acetyl cysteine (NAC), a GSH precursor, prevented enzymatic changes in CAT, Se-dependent GSH-Px, GR, SOD1 activities, and significantly decreased SOD2 activity following exposure to thiram. GSH(total)/GSSG ratio was restored to the control value. This study suggests that following the changes in antioxidant defense systems thiram can act through the production of free radicals.     

(E)‐2‐Benzylidene‐4‐phenyl‐1,3‐diselenole ameliorates signals of renal injury induced by cisplatin in rats

The present study investigated the protective role of antioxidant (E)‐2‐benzylidene‐4‐phenyl‐1,3‐diselenole (BPD), an organoselenium compound, against the renal injury induced by cisplatin in rats. Canola oil or BPD (50 mg kg^?1) was administered orally by gavage once a day for 6 days to rats. The first dose of BPD was given 24 h before a single intraperitoneal injection of saline or cisplatin (7 mg kg^?1). At day 7, animals were killed and parameters related to renal injury were determined. The histological analysis showed that cisplatin caused renal injury in rats, which was accompanied by an increase in urea and creatinine levels in plasma. The increase of plasma creatinine levels negatively correlated with renal antioxidant defenses including ascorbic acid (AA) and reduced glutathione (GSH) content as well as glutathione S‐transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities. As revealed by histological analysis, BPD ameliorated tubular injury in rat kidney and reduced plasma markers altered by cisplatin. The administration of BPD to rats attenuated the reduction of renal AA and GSH content in animals exposed to cisplatin. The decrease of GST activity, but not GPx and CAT activities, in rats exposed to cisplatin was totally reversed by BPD administration. BPD was also effective in attenuating the inhibition of a sulfhydryl enzyme sensitive to oxidative stress, δ‐aminolevulinic dehydratase, in kidneys of rats exposed to cisplatin. The present study demonstrated that BPD reduced renal injury induced by cisplatin in rats and this effect seems to be related to antioxidant mechanisms. Copyright © 2012 John Wiley & Sons, Ltd.     

Genotoxicity assessment and oxidative stress responses in freshwater African catfish Clarias gariepinus exposed to fenthion formulations

Fenthion is one of the most widely used organophosphate insecticides for the control of many varieties of pests in Nigeria. The genotoxic effect of the pesticide was evaluated in the blood erythrocytes of Clarias gariepinus using the micronucleus (MN) test. The oxidative stress parameters were also studied in the liver and gill tissues. Fish were exposed to 2.0, 4.0, and 8.0?mgL^?1 of fenthion and sampling was done on days 1, 7, 14, 21 and after 7-day recovery. Micronuclei induction was highest (7.55) on day 14 at all concentrations in the peripheral blood cells. Oxidative stress was evidenced by increased lipid peroxidation (LPO). Maximum LPO values of 62.47% and 71.17% were observed in the gill and liver tissues respectively in C. gariepinus exposed to 8.0?mgL^?1 concentration of fenthion. There were alterations in the values of reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) during the exposure and recovery periods. The 7-day recovery period was not adequate to eliminate fenthion-induced changes as LPO, CAT, and GR activity remain elevated. However, MN frequency and activity of SOD, GSH, and GPx (except at 8.0?mgL^?1) recovered. The present findings give further credence on the integrated use of MN test and oxidative stress parameters in risk assessment of pollutants in aquatic ecosystem.