Streptozotocin may provide protection against subsequent oxidative stress of endotoxin or streptozotocin in rats

Endotoxin lipopolysaccharide (LPS) and streptozotocin-induced diabetes are known to cause oxidative stress in vivo. There is some evidence that a sublethal dose of LPS provides protection against subsequent oxidative stress. Because of its wide use as a diabetogenic agent, this study was undertaken to determine if streptozotocin can likewise provide a protective effect against further oxidative stress in rats. Female Sprague–Dawley rats were given streptozotocin (50 mg/kg intraperitoneally once) prior to exposure to either bacterial endotoxin from Salmonella abortus equii (5 mg/kg intraperitoneally) or three additional daily doses of streptozotocin (50 mg/kg intraperitoneally). One week after LPS or streptozotocin treatments, oxidative stress was determined by measuring changes in antioxidant activity (glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, glutathione S-transferase, and γ-glutamyltranspeptidase) and in concentrations of glutathione, nitrite, and thiobarbituric acid reactants in liver, kidney, intestine, and spleen. High levels of some antioxidants in the LPS-control and streptozotocin-control rats, in contrast to normal levels found in diabetes + LPS and multidose-streptozotocin rats, suggest that streptozotocin, like LPS, may confer a protective effect against subsequent oxidative stress. © 1998 John Wiley & Sons, Inc. J Biochem Toxicol 12: 143–149, 1998     

Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats

Free radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. This in vivo study has examined whether subacute administration of pycnogenol, a French pine bark extract containing procyanidins that have strong antioxidant potential, alters biomarkers of oxidative stress in normal and diabetic rats. Diabetes was induced in female Sprague-Dawley rats by a single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body weight, increased serum glucose concentrations, and an increase in liver weight, liver/body weight ratios, total and glycated hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after pycnogenol treatment. Additionally, diabetic rats treated with pycnogenol had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms in streptozotocin-induced diabetic rats.     

Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver

Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver damage, though the mechanism is poorly characterized. We evaluated the effect of DDS administration to male and female rats (30 mg/kg body wt, twice a day, for 4 days) on liver oxidative stress through assessment of biliary output and liver content of reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and expression/activities of the main antioxidant enzymes glutathione peroxidase, superoxide dismutase, catalase and glutathione S-transferase. The influence of DDS treatment on expression/activity of the main DDS phase-II-metabolizing system, UDP-glucuronosyltransferase (UGT), was additionally evaluated. The involvement of dapsone hydroxylamine (DDS-NHOH) generation in these processes was estimated by comparing the data in male and female rats since N-hydroxylation of DDS mainly occurs in males. Our studies revealed an increase in the GSSG/GSH biliary output ratio, a sensitive indicator of oxidative stress, and in lipid peroxidation, in male but not in female rats treated with DDS. The activity of all antioxidant enzymes was significantly impaired by DDS treatment also in male rats, whereas UGT activity was not affected in any sex. Taken together, the evidence indicates that DDS induces oxidative stress in rat liver and that N-hydroxylation of DDS was the likely mediator. Impairment in the activity of enzymatic antioxidant systems, also associated with DDS-NHOH formation, constituted a key aggravating factor.     

Effect of peroxisome proliferators on the methylation and protein level of the c-myc protooncogene in B6C3F1 mice liver

Peroxisome proliferators in general are nongenotoxic mouse liver carcinogens for which DNA hypomethylation and altered gene expression are proposed mechanisms. Therefore, the peroxisome proliferators 2,4-dichlorophenoxyacetic acid (2,4-D), dibutyl phthalate (DBP), gemfibrozil, and Wy-14,643 were evaluated for the ability to alter the methylation and expression of the c-myc protooncogene. Male B6C3F1 mice were administered for 6 days in their diet Wy-14,643 (5-500 ppm), 2,4-D (1,680 ppm), DBP (20,000 ppm), or gemfibrozil (8,000 ppm). All four peroxisome proliferators caused hypomethylation of the c-myc gene in the liver. Wy-14,643 appeared to be the most efficacious with a threshold between 10 and 50 ppm. The level of the c-myc protein was increased by Wy-14,643, but not the other peroxisome proliferators. When female B6C3F1 mice received a two-thirds partially hepatectomy and 16 h later were administered 50 mg/kg Wy-14,643 by gavage, hypomethylation of the gene occurred 24 h later. Hypomethylation was not found in mice that received Wy-14,643 following a sham operation. Hypomethylation of the c-myc gene within 24 h of administering Wy-14,643 after a partial hepatectomy but not after a sham operation supports the hypothesis that the peroxisome proliferators prevent methylation of hemimethylated sites formed by DNA replication.     

Energy intake,oxidative stress and antioxidant in mice during lactation

Reproduction is the highest energy demand period for small mammals, during which both energy intake and expenditure are increased to cope with elevated energy requirements of offspring growth and somatic protection. Oxidative stress life history theory proposed that reactive oxygen species(ROS) were produced in direct proportion to metabolic rate, resulting in oxidative stress and damage to macromolecules. In the present study, several markers of oxidative stress and antioxidants activities were examined in brain, liver, kidneys, skeletal muscle and small intestine in non-lactating(Non-Lac) and lactating(Lac) KM mice. Uncoupling protein(ucps) gene expression was examined in brain, liver and muscle. During peak lactation, gross energy intake was 254% higher in Lac mice than in Non-Lac mice. Levels of H2O2 of Lac mice were 17.7% higher in brain(P<0.05), but 21.1%(P<0.01) and 14.5%(P<0.05) lower in liver and small intestine than that of Non-Lac mice. Malonadialdehyde(MDA) levels of Lac mice were significantly higher in brain, but lower in liver, kidneys, muscle and small intestine than that of Non-Lac mice. Activity of glutathione peroxidase(GSH-PX) was significantly decreased in brain and liver in the Lac group compared with that in the Non-Lac group. Total antioxidant capacity(TAOC) activity of Lac mice was significantly higher in muscle, but lower in kidneys than Non-Lac mice. Ucp4 and ucp5 gene expression of brain was 394% and 577% higher in Lac mice than in Non-Lac mice. These findings suggest that KM mice show tissuedependent changes in both oxidative stress and antioxidants. Activities of antioxidants may be regulated physiologically in response to the elevated ROS production in several tissues during peak lactation. Regulations of brain ucp4 and ucp5 gene expression may be involved in the prevention of oxidative damage to the tissue.     

Influences of different stress models on the antioxidant status and lipid peroxidation in rat erythrocytes

The aim of this study was to investigate the influences of different stress models on the antioxidant status and lipid peroxidation (LPO) in erythrocytes of rats. Swiss-Albino female rats (3 months old) were used in this study. Rats were randomly divided into the following four groups; control group (C), cold stress group (CS), immobilization stress group (IS) and cold+immobilization stress group (CS+IS). Control group was kept in an animal laboratory (22 ±2°C). Rats in CS group were placed in cold room (5°C) for 15 min/day for 15 days. Rats in IS group were immobilized for 180 min/day for 15 days. Rats in CS+IS group were exposed to both cold and immobilization stresses for 15 days. At the end of experimental periods, the activities of glucose-6-phosphate dehydrogenase (G-6-PD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and concentration of reduced glutathione (GSH) were measured. LPO was determined by measuring the contents of thiobarbituric acid-reactive substances (TBARS). Cu,Zn-SOD activity and TBARS concentration were increased after cold and immobilization stresses, but CAT and GSH-Px activities and GSH levels were decreased. Immobilization stress decreased the activity of G-6-PD. The activities of G-6-PD, CAT and GSH-Px, and the level of GSH were lower in CS+IS group than in the control group. Cu,Zn-SOD activity and TBARS levels were increased in CS+IS group when compared with the control group. From these findings, three stress models are thought to cause oxidative stress.     

Differential effects of short-term lindane administration on parameters related to oxidative stress in rat liver and erythrocytes

Parameters related to oxidative stress in rat liver and erythrocytes were studied after short-term administration (60 and 90 days) of 1000 ppm of lindane in the diet. Lindane induced an oxidative stress condition in the liver, which is related to an enhancement in microsomal NADPH-cyto-chrome c reductase and NADPH oxidase activities, superoxide radical formation and cytochrome P450 content, produced independently of the time of treatment. Also, decreased activities of glutathione peroxidase and catalase were concomitantly observed. Although these changes were paralleled by an increase in lipid peroxidation indices, such as production of thiobarbituric acid reactants and spontaneous chemiluminescence, no evidence of liver injury was obtained. Lindane treatment did not exert quantitatively important changes in the pro-oxidant/anti-oxidant status of the erythrocyte, with reduction in the red blood cell mass possibly reflecting actions of the insecticide on the eryth-ropoietic process.     

Influence of treatment of diabetic rats with combinations of pycnogenol, β‐carotene,and α‐lipoic acid on parameters of oxidative stress

Treatment with antioxidants may act more effectively to alter markers of free radical damage in combinations than singly. This study has determined whether treatment with combinations of pycnogenol, β‐carotene, and α‐lipoic acid was more effective at reducing oxidative stress in diabetic rats than treatment with these antioxidants alone. It is not feasible, based on this study, to assume that there are interactive effects that make combinations of these antioxidants more effective than any one alone to combat oxidative stress. Female Sprague‐Dawley rats, normal and streptozotocin‐induced diabetic, were treated (10 mg/kg/day ip for 14 days) with pycnogenol, β‐carotene, pycnogenol + β‐carotene, or pycnogenol + β‐carotene + α‐lipoic acid; controls were untreated. Concentrations of thiobarbituric acid reactive substances, glutathione and glutathione disulfide, and activities of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase were measured in liver, kidney, and heart. Four types of effects were observed: (1) treatment with β‐carotene alone either reversed (cardiac glutathione disulfide) or elevated (cardiac glutathione, hepatic glutathione peroxidase activity) levels seen in diabetic animals; (2) β‐carotene alone produced no effect, but pycnogenol both alone and in combinations elevated (renal glutathione peroxidase and glutathione reductase activities, hepatic glutathione reductase activity and glutathione disulfide) or depressed (cardiac glutathione disulfide) levels seen in untreated diabetic animals; (3) all treatments with antioxidants, either alone or in combination, either normalized (lipid peroxidation in all tissues), elevated (hepatic GSH, cardiac glutathione peroxidase activity), or had no effect on (activities of hepatic catalase and superoxide dismutase in all tissues) levels seen in diabetic animals; (4) in only one case (cardiac glutathione reductase activity) levels in diabetic animals treated with combinations of antioxidants were normal, but elevated in animals treated with either antioxidant alone. Antioxidant effects seem to be dependent on the nature of the antioxidant used and not on combination effects. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:345–352, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20046     

Protective effect of arjunolic acid against arsenic-induced oxidative stress in mouse brain

Arsenic, a notoriously poisonous metalloid, is ubiquitous in the environment, and it affects nearly all organ systems of animals including humans. The present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid against arsenic-induced oxidative damage in murine brain. Sodium arsenite was selected as a source of arsenic for this study. The free-radical-scavenging activity and the in vivo antioxidant power of arjunolic acid were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of sodium arsenite at a dose of 10 mg/kg body weight for 2 days significantly decreased the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase, the level of cellular metabolites, reduced glutathione, total thiols and increased the level of oxidized glutathione. In addition, it enhanced the levels of lipid peroxidation end products and protein carbonyl content. Treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days prior to arsenic administration almost normalized above indices. Histological findings due to arsenic intoxication and arjunolic acid treatment supported the other biochemical changes in murine brains. Results of 2,2-diphenyl-1-picryl hydrazyl radical scavenging and ferric reducing/antioxidant power assays clearly showed the in vitro radical scavenging as well as the in vivo antioxidant power of arjunolic acid, respectively. The effect of a well-established antioxidant, vitamin C, has been included in the study as a positive control. Combining all, results suggest that arjunolic acid possessed the ability to ameliorate arsenic-induced oxidative insult in murine brain and is probably due to its antioxidant activity.     

Inhibition of monoterpene biosynthesis accelerates oxidative stress and leads to enhancement of antioxidant defenses in leaves of rubber tree (Hevea brasiliensis)

This paper mainly studies the possible antioxidant of monoterpene and effects of its absence on other antioxidant defense. The leaves of rubber tree (Hevea brasiliensis) were fed with fosmidomycin through transpiration stream, in the dark, at room temperature for 2 h, and were then exposed to bright illumination (1,500 μmol m⁻² s⁻¹) and moderately high temperature (30°C) for 1 h. The results showed that monoterpene biosynthesis in leaves was considerably inhibited by fosmidomycin, and the elevated levels of both hydrogen peroxide and malondialdehyde were observed in the leaves fed with fosmidomycin (LFF). Compared to the control leaves (CK), ∆F/F _m′ in the LFF was markedly lower during the first 20 min; however, there were no significant differences in non-photochemical quenching and photosynthetic pigments (chlorophylls and carotenoids). In contrast, the activities of antioxidant enzymes (superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase) were enhanced in the LFF. Meanwhile, the contents of antioxidant metabolites (ascorbate and glutathione) were also elevated in the LFF, when compared with the CK. The results obtained here suggest that monoterpene may be very effective molecule in protecting plants against oxidative stress, the absence of monoterpene leads to the increased responses of the enzymatic and non-enzymatic antioxidant defenses to oxidative stress, and the enhancement of the enzymatic and non-enzymatic antioxidant defenses may, in part, compensate for the loss of antioxidant conferred by monoterpene.     

Effect of copper intoxication on rat liver proteasome activity: relationship with oxidative stress

Copper toxicity is associated with formation of reactive oxygen species, which are capable to oxidize proteins. The selective removal of the latter by the 20S proteasome is considered an essential part of the cell antioxidant defense system. The aim of the present study was to investigate whether peptidase activities of rat liver proteasomes were affected by chronic (40 mg CuSO(4)/rat/daily with the drinking water for 2 weeks) and acute (20 mg/kg CuSO(4), s.c.) copper treatment. To evaluate the role of proteasome, its inhibitor MG132 was also used. The degree of copper-induced oxidative stress (OS), established by measuring lipid peroxidation, protein oxidation, and cellular glutathione level, as well as activities of antioxidant enzymes--catalase, superoxide dismutase, and gultathionine peroxidase, depended on the mode of copper administration. Chronic copper administration (mild oxidative stress) did not affect proteasome activities, whereas acute copper treatment (severe oxidative stress) caused a decline in chymotryptic- and tryptic-like activities. The treatment of copper-loaded animals with MG132 did not change copper-induced alterations in the tested indices, except an additional increase in protein oxidation and inhibition of glutathionine peroxidase activity. The results suggested that the in vivo copper-induced oxidative stress was associated with changes in the catalytic activity of proteasome.     

Ncb5or deficiency increases fatty acid catabolism and oxidative stress

The endoplasmic reticulum-associated NADH cytochrome b(5) oxidoreductase (Ncb5or) is widely distributed in animal tissues. Ncb5or(-/-) mice develop diabetes at age 7 weeks and have increased susceptibility to the diabetogenic oxidant streptozotocin. Ncb5or deficiency also results in lipoatrophy and increased hepatocyte sensitivity to cytotoxic effects of saturated fatty acids. Here we investigate the mechanisms of these phenomena in prediabetic Ncb5or(-/-) mice and find that, despite increased rates of fatty acid uptake and synthesis and higher stearoyl-CoA desaturase (SCD) expression, Ncb5or(-/-) liver accumulates less triacylglycerol (TAG) than wild type (WT). Increased fatty acid catabolism and oxidative stress are evident in Ncb5or(-/-) hepatocytes and reflect increased mitochondrial content, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression, fatty acid oxidation rates, oxidative stress response gene expression, and oxidized glutathione content. Ncb5or(-/-) hepatocytes readily incorporate exogenous fatty acids into TAG but accumulate more free fatty acids (FFA) and have greater palmitate-induced oxidative stress responses and cell death than WT, all of which are alleviated by co-incubation with oleate via TAG channeling. A high fat diet rich in palmitate and oleate stimulates both lipogenesis and fatty acid catabolism in Ncb5or(-/-) liver, resulting in TAG levels similar to WT but increased intracellular FFA accumulation. Hepatic SCD-specific activity is lower in Ncb5or(-/-) than in WT mice, although Ncb5or(-/-) liver has a greater increase in Scd1 mRNA and protein levels. Together, these findings suggest that increased FFA accumulation and catabolism and oxidative stress are major consequences of Ncb5or deficiency in liver.     

Dichloroacetate- and trichloroacetate-induced phagocytic activation and production of oxidative stress in the hepatic tissues of mice after acute exposure

Dichoroacetate (DCA) and trichloroacetate (TCA) are by-products formed during chlorination of the drinking water and were found to be hepatotoxic and hepatocarcinogenic in rodents. In this study, the abilities of the compounds to induce oxidative stress and phagocytic activation have been studied in B6C3F1 mice. Groups of mice were administered 300 mg/kg of either DCA or TCA, p.o, and were sacrificed after 6 or 12 h. Peritoneal lavage cells (PLCs) were isolated and assayed for superoxide anion (SA) production, and hepatic tissues were assayed for the production of SA, lipid peroxidation (LP), and DNA-single strand breaks (SSBs). TCA resulted in significant production of SA in the PLCs, and in the production of SA, LP, and DNA-SSBs in the hepatic tissues, 12 h after dosing, as compared with the control. DCA administration, on the other hand, resulted in significant increases in the productions of LP and DNA-SSBs in the hepatic tissues at both time points, and in SA production in PLCs and hepatic tissues, 6 h after dosing. However, DCA-induced increases in SA production in PLC and hepatic tissues declined at the 12-h time point, reaching control level in the hepatic tissues. These results may implicate the contribution of phagocytic activation to the induction of oxidative stress in the hepatic tissues and also the role of SA production in the induction of LP and/or DNA damage in those tissues, in response to the compounds. The results also suggest studying the involvement of these mechanisms in the long-term hepatotoxicity/hepatocarcinogencity of the compounds.     

Perfluorooctanoic acid has persistent effects on peroxisome proliferation and related parameters in mouse liver

Male C57B1/6 mice were treated for 5 days with 0.05% perfluorooctanoic acid (PFOA) in their diet. This treatment resulted in a potent induction of peroxisomal fatty acid β-oxidation in the liver. In order to investigate recovery from treatment with PFOA, mice were given normal laboratory chow for up to 20 days after termination of PFOA administration. It was established that the activities of peroxisomal lauoryl-CoA oxidase and palmitoyl-CoA oxidation were still elevated 2–3 weeks after termination of treatment. The catalase activity recovered in the cytosolic fraction was also still significantly elevated after 20 days with normal laboratory chow. Furthermore, the protein content of the mitochondrial fraction was increased by PFOA and had not returned to control level at the end of the recovery period. Perfluorooctanoic acid also caused a persistent effect in omega hydroxylation of lauric acid (cytochrome P-452). The activities of cytosolic DT-diaphoreses and glutathione transferase were also enhanced by PFOA. However, these two enzymes recovered relatively rapidly from the treatment (2–20 days). This study reveals two different patterns of recovery from PFOA treatment, one involving parameters that recovered completely, or almost completely, from PFOA treatment after 20 days and another involving parameters that were still elevated at the end of the recovery period.     

Role of peroxisome proliferator-activated receptor-α in fasting-mediated oxidative stress

The peroxisome proliferator-activated receptor-α (PPARα) regulates lipid homeostasis, particularly in the liver. This study was aimed at elucidating the relationship between hepatosteatosis and oxidative stress during fasting. Fasted Ppara-null mice exhibited marked hepatosteatosis, which was associated with elevated levels of lipid peroxidation, nitric oxide synthase activity, and hydrogen peroxide accumulation. Total glutathione (GSH), mitochondrial GSH, and the activities of major antioxidant enzymes were also lower in the fasted Ppara-null mice. Consequently, the number and extent of nitrated proteins were markedly increased in the fasted Ppara-null mice, although high levels of protein nitration were still detected in the fed Ppara-null mice while many oxidatively modified proteins were only found in the fasted Ppara-null mice. However, the role of inflammation in increased oxidative stress in the fasted Ppara-null mice was minimal based on the similar levels of tumor necrosis factor-α change in all groups. These results with increased oxidative stress observed in the fasted Ppara-null mice compared with other groups demonstrate a role for PPARα in fasting-mediated oxidative stress and that inhibition of PPARα functions may increase the susceptibility to oxidative damage in the presence of another toxic agent.     

The modulatory effects of ellagic acid and vitamin E succinate on TCDD-induced oxidative stress in different brain regions of rats after subchronic exposure

The effects of ellagic acid (EA) and vitamin E succinate (VES) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative stress in different brain regions of rats have been studied after subchronic exposure to the compounds. TCDD was administered to groups of rats at a dose of 46 ng/kg/day for 90 days. EA and VES were administered to groups of rats, either separately or simultaneously with TCDD, every other day for 90 days. At the end of the treatment period, animals were sacrificed and brains were dissected to cerebral cortex (Cc), hippocampus (H), cerebellum (C), and brain stem (Bs), and were assayed for production of superoxide anion (SA), lipid peroxidation (LP), and DNA single-strand breaks (SSBs). While TCDD administration to rats resulted in significant production of SA, LP, and DNA SSBs in Cc and H, simultaneous administration of VES or EA with the xenobiotics resulted in significant protection against those effects. The results also indicate that VES provided a better protyection against TCDD-induced effects in brains when compared with EA.     

Reduction of oxidative stress and liver injury following silymarin and praziquantel treatment in mice with Mesocestoides vogae (Cestoda) infection

Oxidative stress is a common mechanism contributing to hepatic damage and fibrogenesis in a variety of liver disorders. The liver is the target organ for many parasitic infections, hence there is a great demand for the development of novel treatment strategies. In the present study conducted on mice infected with larval stage of Mesocestoides vogae, we investigated effects of therapy with praziquantel (PZQ) alone and in combination with silymarin on liver GSH content, lipid peroxidation and larval reduction. Proliferation of liver cells by means of BrdU incorporation into DNA and production of superoxide anions by peritoneal adherent cells was measured to assess the antioxidant activity of silymarin. Drug administration was carried on from day 15 post infection (p.i.) for ten consecutive days and examination was performed during 20 days of follow-up the therapy. Larval M. vogae infection caused liver damage and triggered extensive oxidative stress, resulting in the abolishment of GSH redox balance and ROS-induced lipid peroxidation. PZQ administration caused short-term decline of GSH levels in healthy mice. Low GSH levels in infected mice were elevated gradually in response to the drug, but respiratory burst in cells was not reduced. Silymarin in combination with PZQ showed strong direct antioxidant capacity and stimulated the larvicidal effect of praziquantel. Treatment with PZQ and silymarin downregulated the generation of superoxide anions, prevented lipid peroxidation, stimulated GSH synthesis and proliferation of hepatocytes in infected livers. These findings demonstrated that silymarin can markedly decrease the liver injury and its co-administration with PZQ potentiate effect of therapy, probably due to the down-regulation of fibrogenesis.     

a-Tocopherol Content and a-Tocopherol Transfer Protein Expression in Leukocytes of Children with Acute Leukemia

α-Tocopherol (a form of vitamin E) is a fat-soluble vitamin that can prevent lipid peroxidation of cell membranes. This antioxidant activity of α-tocopherol can help to prevent cardiovascular disease, atherosclerosis and cancer. We investigated the α-tocopherol level and the expression of α-tocopherol transfer protein (α-TTP) in the leukocytes of children with leukemia. The plasma and erythrocyte α-tocopherol levels did not differ between children with leukemia and the control group. However, lymphocytes from children with leukemia had significantly lower α-tocopherol levels than lymphocytes from the controls (58.4±39.0 ng/mg protein versus 188.9±133.6, respectively; p&lt;0.05), despite the higher plasma α-tocopherol/cholesterol ratio in the leukemia group (5.83±1.64 μmol/mmol versus 4.34±0.96, respectively; p&lt;0.05). No significant differences in the plasma and leukocyte levels of isoprostanes (the oxidative metabolites of arachidonic acid) were seen between the leukemia patients and controls. The plasma level of acrolein, a marker of oxidative stress, was also similar in the two groups. Investigation of α-TTP expression by leukocytes using real-time PCR showed no difference between the two groups. These findings suggest that there may be comparable levels of lipid peroxidation in children with untreated leukemia and controls, despite the reduced α-tocopherol level in leukemic leukocytes.     

Effects of temperature on modulation of oxidative stress and antioxidant defenses in testes of tropical tasar silkworm Antheraea mylitta

High temperatures are known to cause physiological stress in organisms. This is often associated with enhanced generation of reactive oxygen species (ROS) leading to oxidative damage. The commercially important tropical tasar silkworm Antheraea mylitta has to endure high summer temperature before egg production on the onset of monsoon. In this study the status of pro-oxidants and antioxidants was studied in the testes of male pupae of tasar silkworm A. mylitta under thermal stress condition. Further, to find out the impact of temperature on physiological activity, oxygen consumption rate was measured. The result indicated higher level of thiobarbituric acid reactive substances (TBARS, as an index of lipid peroxidation) and total hydroperoxides in the male pupae exposed to high temperature (40±1 °C). Similarly, it was found that increased levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), ascorbic acid (ASA) and low molecular thiols (L-SH) in testes are more prominent in high temperature rather than in moderate temperature (35±1 ^oC) suggesting the activation of physiological mechanism to scavenge the ROS produced during stress. Further more, the order of higher level of oxygen consumption rate was observed as high temperature (40±1°C) > moderate temperature (35±1°C) > control groups (28±1°C). Oxygen consumption rate was positively correlated with oxidative stress and antioxidant defence indices. We infer from these findings that the testes of A. mylitta pupae modulate testicular antioxidant responses to thermal stress.