The susceptibility to stress-induced gastric injury of rats exposed to cadmium

In this experimental study, the effect of cadmium on cold and restraint stress-induced gastric lesions has been studied. Rats received 15 μg/mL cadmium-containing water for 30 d, and at the end of this period, they were subjected to cold and restraint stress. Cadmium accumulation in gastric mucosa was associated with increased mucosal lesions, as well as decreased mucin and PGE₂ levels in rats exposed to cadmium. Stress-induced mucosal injury was more pronounced, and the hemoglobin leakage into gastric lumen owing to breakdown in the barrier was 17.30±3.45 μg/mL in control and 35.71±6.18 μg/mL in treated rats. Our data suggest that high cadmium intake facilitates the occurence of stress-induced mucosal lesions by diminishing the mucin content and PGE₂ generation in gastric mucosa.     

Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition

The role of oxidative stress as a mechanism of hepatic injury caused by isoniazid (INH) was investigated in young growing rats. The interaction of moderate and severe degree of protein-energy malnutrition (PEM) was also investigated. Hepatic injury was produced by giving 50 mg/kg/day of INH for 2 weeks. Liver showed kupffer cell hyperplasia along with patchy sinusoidal congestion in hematoxylin (H) and eosin (E) staining. However, diffuse microglobules of oil red O′ positive fat globules could be demonstrated in frozen sections stained with oil red O′. The concomitant elevation of serum ALT/AST added support to the histopathologic injury. Electronmicroscopic analysis revealed the proliferation of rough endoplasmic reticulum in INH-treated groups. The glutathione and related thiols were decreased significantly by INH both in blood and liver tissues, indicating a decrease in protective mechanism. Glutathione reductase activity was elevated concomitantly in both the tissues. A significant decrease in the activity of glutathione peroxidase and catalase is again indicative of diminished capacity to handle the disposal of hydrogen peroxide (H₂O₂) and lipid peroxides. All these alterations indicated that the damage to the liver cell could well be operating through the inefficient disposal of superoxides (O⁻₂) and H₂O₂. A profound decrease in the protective mechanism further aggravated the picture in moderate and severe PEM, which was observed with INH alone. © 1997 John Wiley & Sons, Inc.     

Protective effect of zinc supplementation on blood antioxidant defense system in rats exposed to cadmium

The aim of this study was to assess the effects of subchronic exposure to cadmium (Cd) on the antioxidant defense system of red blood cells (RBCs) and lipid peroxide concentration in the plasma, as well as the possible protective role of zinc (Zn). For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl₂, administered in five doses (each of 0.4 mg Cd/kg BW) on days 5, 10, 15, 20 and 25, giving a total dose of 2 mg Cd/kg BW, i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl₂, administered in doses of 0.8 mg Zn/kg BW, giving a total dose of 4 mg Zn/kg BW, i.p.; a control group received 0.5 mL of physiological saline in an identical manner.

It was shown that exposure to Cd induced a significant decrease (p<0.05) in superoxide dismutase (Zn/Cu SOD) and catalase (CAT) activities in RBCs. Increased lipid peroxide concentration, measured by thiobarbituric acid reactive substances (TBARS), was also observed in the plasma of cadmium-exposed rats. Cd had no effect on glutathione peroxidase (GSH-Px) activity. Zn administration had a beneficial effect on the Cd-induced decrease in Zn/Cu SOD activity (p<0.05) but not on CAT activity. Animals receiving Cd and Zn simultaneously had significantly (p<0.05) lower concentrations of lipid peroxides than rats exposed to Cd alone. Our results indicate that Cd causes oxidative stress and that Zn supply in conditions of exposure to Cd can partially protect against Cd-induced oxidative stress.     

Differential ultrastructural changes in tomato hormonal mutants exposed to cadmium

Cadmium (Cd) is a toxic heavy metal, which can cause severe damage to plant development. The aim of this work was to characterize ultrastructural changes induced by Cd in miniature tomato cultivar Micro-Tom (MT) mutants and their wild-type counterpart. Leaves of diageotropica (dgt) and Never ripe (Nr) tomato hormonal mutants and wild-type MT were analysed by light, scanning and transmission electron microscopy in order to characterize the structural changes caused by the exposure to 1 mM CdCl₂. The effect of Cd on leaf ultrastructure was observed most noticeably in the chloroplasts, which exhibited changes in organelle shape and internal organization, of the thylakoid membranes and stroma. Cd caused an increase in the intercellular spaces in Nr leaves, but a decrease in the intercellular spaces in dgt leaves, as well as a decrease in the size of mesophyll cells in the mutants. Roots of the tomato hormonal mutants, when analysed by light microscopy, exhibited alterations in root diameter and disintegration of the epidermis and the external layers of the cortex. A comparative analysis has allowed the identification of specific Cd-induced ultrastructural changes in wild-type tomato, the pattern of which was not always exhibited by the mutants.     

Grafting of watermelon (Citrullus lanatus cv. Mahbubi) onto different squash rootstocks as a means to minimize cadmium toxicity

To test the possibility that using appropriate rootstocks could improve the tolerance of watermelon to cadmium (Cd) toxicity, a greenhouse experiment was conducted to determine growth and antioxidant activities of watermelons, either nongrafted or grafted onto summer squash and winter squash. We provided nutrient solutions having four levels (0, 50, 100, and 200 μM) of cadmium to treat the plants. Shoot and root biomass reduction were significantly lower in summer squash rootstock-grafted watermelon than winter squash rootstock-grafted and nongrafted watermelons. Cadmium induced a smaller decrease in leaf area index in grafted watermelons compared with nongrafted plants. The Cd- related reductions in chlorophyll content and efficiency of photosynthesis were more severe in nongrafted watermelons compared with dose grafted onto summer squash. Cd accumulation in shoot at the highest dose (200 µM) of CdCl₂ was significantly lower (19.76 mg/kg) in summer squash rootstock-grafted watermelon compared with winter squash rootstock-grafted (37.58 mg/kg) and nongrafted watermelon (72.12 mg/kg). H₂O₂, MDA production and electrolyte leakage of summer squash rootstock-grafted watermelon showed less increase, which was associated with a significant increase in the activities of antioxidant. The improved crop performance of grafted watermelons was attributed to their strong capacity to inhibit Cd accumulation in the aerial parts.     

镉染毒大鼠胫骨骨微结构的活体Micro-CT观察

目的应用Micro-CT研究不同剂量CdCl2染毒后大鼠胫骨松质骨骨小梁密度和骨微结构的差异。方法 24只3月龄雄性SD大鼠随机分成4组,对照组、低剂量组、中剂量组和高剂量组,分别背部皮下注射生理盐水(0.5 mL)和0.1、0.5、1.5 mg/(kg.bw)CdCl2,每周称体重,并根据体重调整注射量。染毒后第8周对所有大鼠左侧胫骨近端进行活体Micro-CT扫描及三维重建。选取距生长板远端0.8、1.2 mm厚的骨组织为感兴趣区域,进行骨形态计量分析。结果镉染毒组大鼠体重和对照组相比有不同程度下降,高剂量组和其他组相比差异有显著性(P<0.05);镉染毒组大鼠骨密度、骨体积分数及骨小梁数量较对照组明显减少,高剂量组与对照组相比差异有显著性(P<0.01);镉染毒组大鼠胫骨骨小梁分离度及骨结构模型指数都较对照组有明显增高,并且随着染毒剂量的增加而升高。二维及三维图象显示,镉作用后大鼠胫骨骨髓腔增宽,骨量、骨小梁数量及骨小梁连接明显减少,板状骨数量减少,杆状骨数量增加。结论镉染毒对大鼠胫骨骨量及骨微观结构有明显损害。     

Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation

The use of cyclosporine A (CsA) as an immunosuppressive agent is often limited owing to its hepatotoxic and nephrotoxic properties. The present study was designed to evaluate the protective effect of metformin and silymarin in a rat model of CsA induced hepatorenal toxicity. The study included seven groups of Wistar albino rats (n = 6 per group): normal control, experimental control (CsA alone, 25 mg/kg), CsA + metformin (50 and 500 mg/kg), CsA + silymarin (50 and 200 mg/kg) and CsA + vitamin E (100 mg/kg). All the drugs were given daily for a period of 21 days by oral gavage and their effect was evaluated on serum levels of organ function markers (serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, bilirubin, urea/blood urea nitrogen, creatinine), markers of oxidative stress (thiobarbituric acid reactive substances, glutathione, superoxide dismutase), inflammation (nitrite, myeloperoxidase, tumour necrosis factor‐alpha, prostaglandin E₂), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling positivity) in addition to tissue histology, cyclooxygenase (COX)‐2 and inducible nitric oxide synthase (iNOS) immunoreactivity. Administration of metformin and silymarin along with CsA ameliorated functional damage to liver and kidneys in a dose‐dependent manner. Significant and comparable improvement in the tissue levels of oxidative stress, inflammation, apoptotic markers was also observed following treatment with both the test drugs. Normalization of histology scores, as well as COX‐2 and iNOS immunoreactivity scores, further strengthened these findings. The hepatoprotective and nephroprotective effects of metformin and silymarin were comparable and matched with that of reference drug, vitamin E. The findings of the present study suggest that both metformin and silymarin have a potential for clinical use in patients receiving long‐term CsA treatment to maintain their liver and kidney functions.     

Effects of ingestion of cadmium-polluted rice or low-dose cadmium-supplemented diet on the endogenous metal balance in female rats

The concentrations of endogenous metal ions in liver, kidney, and bone tissues of female rats were measured after ingestion of cadmium-polluted rice (1.24 ppm as Cd) or cadmium-supplemented rice (1.24 and 4.96 ppm) for 2 or 4 mo. The metal accumulated mainly in the kidneys and in the liver. The concentration of cadmium (Cd) in the kidneys of rats fed a 1.24-ppm Cd-supplemented diet was significantly higher than in the Cd-polluted rice group. After 2 mo, the levels of iron and sodium in the liver were elevated in the Cd-polluted rice group, but not in the 1.24-ppm Cd-supplemented group, as compared to controls. The zinc concentration in the Cd-polluted rice group was decreased. The concentration of copper in the kidneys was increased for all Cd-containing diet groups. After 4 mo, the effects of Cd on essential metals in the Cd-polluted and 1.24-ppm Cd-supplemented groups had almost disappeared, although several metal ions in selected organs in the 4.96-ppm Cd-supplemented group showed more prominent changes than in the group exposed for 2 mo. These results suggest that the effects of short-term exposure to Cd on essential metal balance are stronger for rice-bound Cd than for inorganic Cd, although the absorption rate of Cd in Cd-polluted rice may be lower than that of cadmium chloride added to rice.     

Induction of a putative metallothionein gene in the blood cockle, Anadara granosa, exposed to cadmium

The relationship between a putative metallothionein gene (MT) and exposure to cadmium (Cd) in blood cockles (Anadara granosa) is reported. In a 96-h dose-response experiment, mortality of cockles was found to proportionately increase in the range of 0.2-5.0 mg/l Cd with a calculated LC(50) of 2.94 mg/l. Exposure to 0.25 mg/l Cd for 16 days caused significant increases (P<0.05) in Cd concentrations in whole tissues, gills and hepatopancreas, and the accumulation of Cd in these tissues increased with the duration of exposure. Two cDNA libraries constructed using the hepatopancreas from control and Cd-treated cockles gave titres of 5.62 x 10(5) and 1.94 x 10(5) pfu/microg vector, respectively. A putative MT gene, AnaMT, of 510 nucleotides in length, was isolated from the treated cDNA library using a heterologous probe MT20 from the blue mussel, Mytilus edulis. Northern analyses using AnaMT as a probe indicated low expression of the MT mRNA in control animals. In cockles treated with 0.25 mg/l Cd for 4 days, MT mRNA level increased to approximately 168%, but declined to 108% at day 8. After 12 and 16 days of Cd treatment, expression of the MT gene was 138% and 187%, respectively, compared to the controls. These observations suggest that induction of the MT gene by a sublethal dose of Cd is rapid, occurring within 4 days of treatment.     

Effect of cadmium on antioxidant status in alloxane-induced diabetic rats

Fifty-two healthy Swiss Male Albino rats aged two mo were used in this study. They were divided into four groups: control (C), diabetic (D), cadmium (Cd), and diabetic+Cd (D+Cd) groups. Diabetic condition was induced in D and D+Cd groups by administration of alloxane (5 mg/100 g). After this treatment, CD and D+Cd groups were injected with CdCl₂ ip (2 mg/kg/wk). At the end of the 2-mo experimental period, thiobarbituric acid reactive substances (TBARS), plasma and erythrocyte selenium (SE), plasma ceruloplasmin (Cp), and vitamin E (vit E) were determined in four groups of rats. The erythrocyte Se was lower in the experimental groups than in the controls. Plasma Se was significantly decreased in the D and D+Cd groups compared with the control group. Plasma Cp was unaltered. Plasma vit E was significantly decreased in Cd group in comparison with the C, D, and D+Cd groups.     

Restorative effects of Chrysin pretreatment on oxidant–antioxidant status,inflammatory cytokine production,and apoptotic and autophagic markers in acute paracetamol‐induced hepatotoxicity in rats: An experimental and biochemical study

Paracetamol (PC) is a widely used analgesic and antipyretic drug, but it leads to acute hepatotoxicity at high doses intakes. This study was aimed to investigate the effects of Chrysin (CR) on hepatotoxicity constituted at high doses of PC in rats. Rats were subjected to oral pretreatment of CR (25 and 50 mg/kg b.w.) via feeding needle for 6 days against hepatotoxicity induced by a single dose of PC (500 mg/kg b.w.) administered orally via feeding needles. Although PC increases lipid peroxidation and liver enzyme activities, it has led to reduction of antioxidant enzyme activities. PC induced inflammatory responses by increasing the levels of TNF‐α and IL‐1β. Furthermore, PC caused apoptosis and autophagy by increasing activity of Caspase‐3 and LC3B level. On the other hand, CR therapy significantly regulated these values in rats. This study demonstrated that CR possesses restorative effect against PC‐induced hepatotoxicity by suppressing oxidative stress, inflammation, and apoptotic and autophagic tissue damage.     

Vascular redox imbalance in rats submitted to chronic exercise

Exercise training has been used for treatment/prevention of many cardiovascular diseases, but the mechanisms need to be clarified. Thus, our aim was to compare oxidative stress parameters between rats submitted to a swimming training and sedentary rats (control). Twelve male rats were divided into two groups: control and exercise training. The exercise training had daily 1 h swimming sessions for 8 weeks and a load (5% of its body mass) was placed in rat's tail. Thereafter the animals were killed, aorta and heart were surgically removed and blood was collected. Body mass gain, thiobarbituric acid reactive species (TBARS), carbonyl content, total reactive antioxidant potential (TRAP), total antioxidant reactivity (TAR), superoxide dismutase (SOD) activity and catalase (CAT) activity were evaluted. The trained rats showed a lower body mass gain and no modifications on heart. An increased SOD activity was observed on aorta after the training, but no changes were seen for CAT activity, which led to an increased SOD/CAT ratio. The arterial TBARS was also increased for trained rats. The decrease in TRAP in exercise training was the single modification on plasma. Our findings suggest that the increased SOD activity could play a role in vascular adaptations to exercise training. Copyright © 2010 John Wiley & Sons, Ltd.     

Protective effect of resveratrol against pembrolizumab-induced hepatotoxicity and neurotoxicity in male rats

The present study investigates the effects of resveratrol (RSV) on brain and liver tissues in rats with pembrolizumab (PEMB)-induced toxicity. Obtained for the study were 28 male Sprague-Dawley rats (3–4 months old) which were divided into four groups: Group 1: Control. Group 2: Administered PEMB at 5 mg/kg/day i.p. for a week. Group 3: Administered RSV orally at the dose of 20 mg/kg/day for 30 days by gavage. Group 4: Administered PEMB and RSV at 20 and 5 mg/kg/day RSV, respectively, for 30 days. The results of this study revealed that PEMB leads to a significant increase in thiobarbituric acid reactive substance (TBARS) levels and a significant decrease in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) activities, and glutathione (GSH) levels in the liver and brain tissues. The decreased SOD, CAT, GPx activities, and GSH levels increased significantly following RSV treatment in Group 4. The PEMB treatment showed histopathological alterations associated with strong positive cysteinyl aspartic acid-protease-3 (caspase-3) immunoreactivity, while RSV treatment reduced both the expression of caspase-3 protein and the histopathological changes. RSV administration prevents the biochemical, immunological, and histological alterations induced by PEMB. It can be suggested that the lower caspase-3 immunoreactivity in the PEMB + RSV group than in the PEMB group led to an inhibition of RSV on apoptosis.     

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/ kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats. Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.     

Study on the potential way of hepatic cytotoxicity of N,N‐dimethylformamide

The intermediate metabolites and redox status imbalance were supported as the two major points for N,N‐dimethylformamide (DMF)‐induced hepatotoxicity. However, the potential mechanism has not yet been concerned. By applying two inhibitors, this study tried to seek the major role in DMF‐induced toxicity on HL7702 cell. We observed that DMF induced cell apoptosis through mitochondrial‐dependent and p53 pathway. Inhibition reactive oxygen species by catalase remarkably attenuated the mitochondrial transmembrane potential (MMP), apoptotic proteins, and apoptosis. On the contrary, it reduced the biodegradation rate of DMF by coincubation with CYP2E1 antagonist (DDC) partially reduced late apoptosis. However, the change in MMP, the ratio of Bax to Bcl‐xl, and cleaved‐caspase 9 was not attenuated by DDC. The pathway in DDC coincubation groups was related to the p53 rather than the mitochondrial pathway. Restoring the redox balance during biodegradation is much more effective than attenuating the metabolite rate of DMF. This study may provide a suitable prevention method to occupational workers.     

Antioxidant enzyme activities and lipid peroxidation in the freshwater cladoceran Daphnia magna exposed to redox cycling compounds

Contaminant-related changes in antioxidative processes in the freshwater crustacea Daphnia magna exposed to model redox cycling contaminant were assessed. Activities of key antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferases and levels of lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) and lipofucsin pigment content were determined in D. magna juveniles after being exposed to sublethal levels of menadione, paraquat, endosulfan, cadmium and copper for 48 h. Results denoted different patterns of antioxidant enzyme responses, suggesting that different toxicants may induce different antioxidant/prooxidant responses depending on their ability to produce reactive oxygen species and antioxidant enzymes to detoxify them. Low responses of antioxidant enzyme activities for menadione and endosulfan, associated with increasing levels of lipid peroxidation and enhanced levels of antioxidant enzyme activities for paraquat, seemed to prevent lipid peroxidation, whereas high levels of both antioxidant enzyme activities and lipid peroxidation were found for copper. For cadmium, low antioxidant enzyme responses coupled with negligible increases in lipid peroxidation indicated low potential for cadmium to alter the antioxidant/prooxidant status in Daphnia. Among the studied enzymes, total glutathione peroxidase, catalase and glutathione S-transferase appeared to be the most responsive biomarkers of oxidative stress.     

Persistent impairment of mitochondrial and tissue redox status during lithium-pilocarpine-induced epileptogenesis

Mitochondrial dysfunction and oxidative stress are known to occur following acute seizure activity but their contribution during epileptogenesis is largely unknown. The goal of this study was to determine the extent of mitochondrial oxidative stress, changes to redox status, and mitochondrial DNA (mtDNA) damage during epileptogenesis in the lithium-pilocarpine model of temporal lobe epilepsy. Mitochondrial oxidative stress, changes in tissue and mitochondrial redox status, and mtDNA damage were assessed in the hippocampus and neocortex of Sprague-Dawley rats at time points (24h to 3months) following lithium-pilocarpine administration. A time-dependent increase in mitochondrial hydrogen peroxide (H(2)O(2)) production coincident with increased mtDNA lesion frequency in the hippocampus was observed during epileptogenesis. Acute increases (24-48h) in H(2)O(2) production and mtDNA lesion frequency were dependent on the severity of convulsive seizure activity during initial status epilepticus. Tissue levels of GSH, GSH/GSSG, coenzyme A (CoASH), and CoASH/CoASSG were persistently impaired at all measured time points throughout epileptogenesis, that is, acutely (24-48h), during the 'latent period' (48h to 7days), and chronic epilepsy (21days to 3months). Together with our previous work, these results demonstrate the model independence of mitochondrial oxidative stress, genomic instability, and persistent impairment of mitochondrial specific redox status during epileptogenesis. Lasting impairment of mitochondrial and tissue redox status during the latent period, in addition to the acute and chronic phases of epileptogenesis, suggests that redox-dependent processes may contribute to the progression of epileptogenesis in experimental temporal lobe epilepsy.     

Effects of the Crotalus durissus terrificus snake venom on hepatic metabolism and oxidative stress

Snake venoms present different action mechanisms because of their complex composition, represented mainly by toxins and enzymes. This work aimed to investigate the effects of the Crotalus durissus terrificus(Cdt) venom in the liver. Wistar rats were inoculated intraperitoneally with saline (control) or Cdt venom. After 3, 4, or 6 h, the following parameters were analyzed: (a) hepatic function, (b) oxidative stress parameters, and (c) the metabolism of alanine in the isolated perfused liver. Plasma activities of alanine aminotransferase and aspartate aminotransferase and hepatic glutathione S‐transferase and catalase presented significant elevation in rats inoculated with 300 μg ? kg^?1 Cdt venom. Liver lipoperoxidation was enormously increased by venom doses of 100, 200, and 300 μg ?kg^?1, whereas glutathione S‐transferase was not changed. Perfused livers from rats inoculated with 1500 μg ?kg^?1 venom showed increased production of lactate, pyruvate, and ammonia when alanine was the metabolic substrate. These results demonstrate that the Cdt venom can produce several changes in hepatocytes. The causes of the changes are possibly related to the disequilibrium in the redox homeostasis but also to specific needs of the poisoned organism, for example, an increased supply of lactate and pyruvate in response to an increased activity of the Cori cycle. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:195–203, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20376     

Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4'-dipyridyl disulfide

Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS is very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma-glutamyl-cysteine synthetase) and, particularly, GLR1 (glutathione reductase) are required for survival on DPS. DPS is uniquely thiol-specific, and we found that the cellular mechanisms for DPS detoxification differ substantially from that of the commonly used thiol oxidant diamide. In contrast to this oxidant, the full antioxidant pools of glutathione (GSH) and thioredoxin are required for resistance to DPS. We found that DPS-sensitive mutants display increases in the disulfide form of GSH (GSSG) during DPS exposure that roughly correlate with their more oxidizing GSH redox potential in the cytosol and their degree of DPS sensitivity. DPS seems to induce a specific disulfide stress, where an increase in the cytoplasmic/nuclear GSSG/GSH ratio results in putative DPS target(s) becoming sensitive to DPS.     

Hyper-osmoregulatory capacity of the Chinese mitten crab (Eriocheir sinensis) exposed to cadmium; acclimation during chronic exposure

The aim of this study was to evaluate the effects of waterborne cadmium on hyper-osmoregulatory capacity of the Chinese mitten crab Eriocheir sinensis acclimated to freshwater. For this purpose, crabs were submitted to acute (0.5 mg Cd L(-1) for 1, 2 or 3 days), chronic (10 or 50 microg Cd L(-1) for 30 days) or chronic, immediately followed by acute, exposure. While no effect was observed after 1 or 2 days, hemolymph osmolality, Na(+) and Cl(-) concentrations were significantly reduced after 3 days of acute exposure. Under this latter condition, the respiratory anterior gill ultrastructure, Na(+)/K(+)-ATPase and cytochrome c oxidase activities were significantly impaired. In contrast, the osmoregulatory posterior gill was unaffected for all treatments. As a consequence, we suggest that the observed hyper-osmoregulatory capacity impairment is the result of increased dissipative flow of ions and/or water through anterior gills. In contrast to acute exposure, chronic exposure did not induce any observable effect. However, crabs submitted to a known deleterious acute condition (0.5 mg Cd L(-1) for 3 days) directly after chronic exposure to 50 microg Cd L(-1) for 30 days showed normal hyper-osmoregulatory capacity with no change in gill Na(+)/K(+)-ATPase activity, and only little disturbance of anterior gill ultrastructure. These results demonstrate that a chronic cadmium exposure can induce acclimation mechanisms related to osmoregulation in this euryhaline decapod crustacean.