Thyroid hormone-induced haemoglobin changes and antioxidant enzymes response in erythrocytes

Thyroid hormones modulate haemoglobin and reactive oxygen species (ROS) production, leading to antioxidant changes. This study evaluated the antioxidant response to ROS in erythrocytes in hypothyroid and hyperthyroid rats. Wistar rats were divided into four groups: control; hyperthyroid (T4-12 mg 1(-1) in drinking water); sham operated (simulation of thyroidectomy); and hypothyroid (thyroidectomized). Four weeks after, blood was collected and haemoglobin and T(4) levels, lipid peroxidation (LPO), protein oxidation, superoxide dismutase (SOD), catalase (CAT) , glutathione S-transferase (GST) and glutathione peroxidase (GPx) activities, and total radical antioxidant potential (TRAP) were measured. SOD, CAT and GST immunocontent was evaluated. Haemoglobin levels were increased in hyperthyroid erythrocytes. LPO and carbonyls were augmented (65% and 55%, respectively) in hyperthyroid and reduced (31% and 56%, respectively) in hypothyroid group. SOD and CAT activities have not changed, as well as CAT immunocontent. TRAP was diminished in both hyperthyroid and hypothyroid groups (36% and 37%, respectively). GST activity and immunocontent, as well as GPx activity, were increased in hyper and hypothyroid rats. The data suggest that thyroid hormone changes determine ROS concentration changes and decrease of some antioxidant defences that would lead to a compensatory answer of the GST and GPx enzymes, which could be consider as credible biomarkers.     

The effects of selenium on oxidative stress biomarkers in the freshwater characid fish matrinxã, Brycon cephalus (Günther, 1869) exposed to organophosphate insecticide Folisuper 600 BR (methyl parathion)

Methyl parathion (MP), an organophosphate widely applied in agriculture and aquaculture, induces oxidative stress due to free radical generation and changes in the antioxidant defense system. The antioxidant roles of selenium (Se) were evaluated in Brycon cephalus exposed to 2 mg L(-1) of Folisuper 600 BR (MP commercial formulation - MPc, 600 g L(-1)) for 96 h. Catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (LPO) levels in the gills, white muscle and liver were evaluated in fish fed on diets containing 0 or 1.5 mg Se kg(-1) for 8 weeks. In fish treated with a Se-free diet, the MPc exposure increased SOD and CAT activities in all tissues. However, the GPx activity decreased in white muscle and gills whereas no alterations were observed in the liver. MPc also increased GST activity in all tissues with a concurrent decrease in GSH levels. LPO values increased in white muscle and gills and did not change in liver after MPc exposure. A Se-supplemented diet reversed these findings, preventing increases in LPO levels and concurrent decreases in GPx activity in gills and white muscle. Similarly, GSH levels were maintained in all tissue after MPc exposure. These results suggest that dietary Se supplementation protects cells against MPc-induced oxidative stress.     

Lead-induced lipid peroxidation and antioxidant defense components of developing chick embryos.

Administration of lead (1.25 and 2.5 mumol/kg egg weight) to 14-day-old chick embryos enhanced the level of lipid peroxides (LPO) in tissues of liver, brain, and heart. Accumulation of LPO was maximum at 9 h after treatment with lead and returned to normal level by 72 h. Further, we have studied the levels of glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. At 9 h posttreatment, the hepatic GR was reduced significantly with the induction of GST and considerable depletion of GSH. However, in brain and heart, both GR and GST activities were unaltered with significant reduction of GSH. Further, an increase of non-Se-dependent GPx and SOD activities were observed in liver, brain, and heart. Similarly, at 72 h, although the GPx activity was found decreased in liver and brain, the GST, catalase, and SOD activities were significantly increased in all the three tissues alike, suggesting tissue-specific changes of antioxidant defense components in response to lead treatment. Our results suggests that the elevated levels of GST, SOD, and catalase at 72 h were successful in bringing LPO levels back to normal.     

The association between oxidative stress and obstructive lung impairment in patients with COPD

An oxidant/antioxidant imbalance is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that antioxidant capacity reflected by erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities, and serum levels of the lipid peroxidation product malondialdehyde (MDA), may be related to the severity of obstructive lung impairment in patients with COPD. Erythrocyte GPx, SOD and CAT activities, and serum levels of MDA were measured in 79 consecutive patients with stable COPD. Pulmonary functional tests were assessed by body plethysmography. Moderate COPD (FEV1 50-80%) was present in 23, and severe COPD (FEV1 < 50%) in 56 patients. Erythrocyte GPx activity was significantly lower, and serum MDA levels were significantly higher in patients with severe COPD compared to patients with moderate COPD (GPx: 43.1+/-1.5 vs. 47.7+/-2.9 U/gHb, p<0.05, MDA: 2.4+/-0.1 vs. 2.1+/-0.1 nmol/ml, p<0.05). Linear regression analysis revealed a significant direct relationship between FEV1 and erythrocyte GPx activity (r = 0.234, p<0.05), and a significant inverse relationship between FEV1 and serum MDA levels (r = -0.239, p<0.05). However, no differences were observed in the erythrocyte SOD and CAT activities between the two groups of patients with different severity of COPD. Findings of the present study suggest that antioxidant capacity reflected by erythrocyte GPx activity and serum levels of the lipid peroxidation product MDA are linked to the severity of COPD.     

Oxidative stress biomarkers in the freshwater characid fish, Brycon cephalus, exposed to organophosphorus insecticide Folisuper 600 (methyl parathion)

Methyl parathion (MP) is an organophosphorus insecticide used worldwide in agriculture and aquaculture due to its high activity against a broad spectrum of insect pests. The effect of a single exposure to 2 mg L(- 1) of a commercial formulation of MP (MPc: Folisuper 600(R), MP 600 g L(- 1)) on catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (LPO) of the liver, white muscle and gills of Brycon cephalus was evaluated after 96 h of treatment. MPc exposure resulted in a significant induction of SOD, CAT and GST activity in all tissues. However, the GPx activity decreased significantly in white muscle and gills, whereas no alterations were observed in hepatic GPx activity. MPc also induced a significant increase in LPO values in the white muscle and gills, while hepatic LPO levels did not show any significant alteration. The current data suggest that MPc has oxidative-stress-inducing potential in fish, and that gills and white muscle are the most sensitive organs of B. cephalus, with poor antioxidant potentials. The various parameters studied in this investigation can also be used as biomarkers of exposure to MPc.     

Antioxidant response and oxidative stress levels in Macrobrachium borellii (Crustacea: Palaemonidae) exposed to the water-soluble fraction of petroleum

The aim of the present work was to evaluate the effect of the water soluble fraction of hydrocarbons (WSF) on the antioxidant status of the freshwater prawn Macrobrachium borellii. First, seasonal variations were studied in a non-polluted area. Hepatopancreas and gills showed season-related fluctuations in catalase (CAT), glutathione-S-transferase (GST) activities and in lipid peroxidation levels (LPO), but not in superoxide dismutase (SOD). Then, adults were exposed semi-statically to sublethal doses for 7days. CAT, SOD, GST, and glutathione peroxidase (GPx) activities and LPO, reduced glutathione (GSH) and protein oxidation (PO) levels were determined. Exposed individuals showed significant increases in CAT, SOD, and GST activities in hepatopancreas and CAT activity in gills. GPx activity did not vary in either tissues. While LPO levels increased, GSH levels decreased significantly in hepatopancreas of exposed animals, but PO levels showed no variation. Induction of SOD was also assessed by Real-time PCR mRNA expression in hepatopancreas. The non-enzymatic antioxidant activity was also tested; ABTS 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) was higher in hemolymph of treated-prawns compared to controls, but ferric reducing activity of plasma assay (FRAP) values did not change. Taken together, the present results indicated that the antioxidant defenses of M. borellii, mainly in hepatopancreas, were significantly affected by aquatic hydrocarbon contamination, regardless of the season.     

Fenugreek seeds modulate 1,2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis

1,2-dimethylhydrazine (DMH) is a colon carcinogen which undergoes oxidative metabolism in the liver. We have investigated the modulatory effect of fenugreek seeds (a spice) on colon tumor incidence as well as hepatic lipid peroxidation (LPO) and antioxidant status during DMH-induced colon carcinogenesis in male Wistar rats. In DMH treated rats, 100% colon tumor incidence was accompanied by enhanced LPO and a decrease in reduced glutathione (GSH) content as well as a fall in glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities. Inclusion of fenugreek seed powder in the diet of DMH treated rats reduced the colon tumor incidence to 16.6%, decreased the LPO and increased the activities of GPx, GST, SOD and CAT in the liver. We report that fenugreek modulates DMH-induced hepatic oxidative stressduring colon cancer     

Antitumor and cytotoxic effects of Phyllanthus polyphyllus on Ehrlich ascites carcinoma and human cancer cell lines

To evaluate the antitumor and cytotoxic activity of methanol extract of Phyllanthus polyphyllus (MPP) in mice and human cancer cell lines, the antitumor activity of MPP was evaluated against an Ehrlich ascites carcinoma (EAC) tumor model. The activity was assessed using survival time, hematological studies, lipid peroxidation (LPO), antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione S-transferase (GST), solid tumor mass, and short-term in vitro cytotoxicity. The cytotoxic activity of MPP was evaluated using human breast cancer (MCF7), colon cancer (HT29), and liver cancer (HepG2) cell lines Oral administration of MPP (200 and 300 mg/kg) increased the survival time and significantly reduced the solid tumor volume in a dose-dependent manner. Hematological parameters, protein, and packed cellular volume (PCV), which were altered by tumor inoculation, were restored. MPP significantly decreased the levels of LPO, GPx, GST, and significantly increased the levels of SOD and CAT. In a cytotoxicity study against human cancer cell lines, MPP was found to have IC50 values of 27, 42 and 38 microg/ml on MCF-7, HT-29, and HepG2 cells respectively. MPP possessed significant antitumor and cytotoxic activity on EAC and human cancer cell lines.     

Erythrocyte antioxidant defense response against cigarette smoking in humans--the glutathione S-transferase vulnerability

Cigarette smoking leads to uptake of a multitude of reactive chemicals including many electrophiles and may also give rise to oxidative stress. Human red blood cells are important targets for electrophilic and oxidant foreign compounds. We investigated the oxidative stress in erythrocytes upon cigarette smoking, and the response of antioxidant defense system against it. With this aim, simultaneous determination of erythrocyte superoxide dismutase (SOD), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT), glutathione S-transferase (GST) activities and plasma levels of thiobarbituric acid reactive substances (TBARS), and the degree of erythrocyte membrane lipid peroxidation (EMLP) were carried out in blood samples of smokers and their controls. Plasma TBARS levels and EMLP in smokers were significantly higher than the control levels (p < 0.01 and p < 0.005, respectively). SOD activity was diminished in smokers compared to nonsmoker controls (p < 0.005). Erythrocyte Se-GPx activity was also found significantly diminished in smokers (p < 0.005), while plasma Se-GPx activity was not changed. We observed that erythrocyte CAT activity was not different in smokers compared to nonsmoker controls. We found that the erythrocyte GST activity is significantly lower in young adult smokers (3.03 +/- 0.18 U/mg protein; mean +/- SEM; n = 46) than in nonsmoking contemporaries (3.98 +/- 0.26 U/mg protein; mean +/- SEM; n = 41). Together with previously reported data, it can be concluded that the decrease in GST activity leads to extra GST synthesis during erythrocyte proliferation. The same data were also analyzed for the sex differences. The statistically significant differences remained the same between nonsmoker and smoker females. Only EMLP degree and SOD activity were significantly different between nonsmoker and smoker males; however, when compared the parameters between male and female nonsmokers, GST activity was found to be significantly higher in females than that of males.     

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

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

Seasonal changes in antioxidant defence system of liver and gills of Salmo trutta caspius, Salmo trutta labrax and Salmo trutta macrostigma

Seasonal changes in antioxidant enzyme activities (superoxide dismutase, SOD, EC 1.15.1.1; catalase, CAT, EC 1.11.1.16; glutathione peroxidase, GPx, EC 1.11.1.9; glutathione reductase, GR, EC 1.6.4.2; glucose-6-phosphate dehydrogenase, G6PD, EC 1.1.1.49 and glutathione S -transferase, GST, EC 1.5.1.18) and lipid peroxidation (LPO) levels of livers and gills of female Caspian trout Salmo trutta caspius , Black Sea trout Salmo trutta labrax and mountain trout Salmo trutta macrostigma were investigated. SOD, CAT, GPx, G6PD and GST activities were higher in liver compared to gills of all sub-species; concomitantly, the GR activity was also higher in the livers of S. t. caspius and S. t. labrax , but the reverse was seen in S. t. macrostigma . LPO levels were higher in the gills compared to the liver of all sub-species. There was no general trend in the seasonal changes in the gill antioxidant enzyme (AE) activities or LPO levels. Higher AE activities, however, were found in the liver of each sub-species during autumn, and this coincided with an increase in the gonado-somatic index.     

Anticancer potential of rhamnocitrin 4′-β-d-galactopyranoside against N-diethylnitrosamine-induced hepatocellular carcinoma in rats

The hepatoprotective activity of flavonoid rhamnocitrin 4′-β-d-galactopyranoside (RGP) obtained from leaves of Astragalus hamosus L. against N-diethylnitrosamine (DENA)-induced hepatic cancer in Wistar albino rats was evaluated. Hepatic cancer in rats was induced by single-dose intraperitoneal administration of DENA (200 mg/kg). Induction of hepatic cancer was confirmed after 7 days of DENA administration by measurement of elevated level of serum α-feto protein (AFP). Administration of DENA in a single dose lofted the levels of serum biochemical parameters like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein and AFP. Antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and lipid per oxidation (LPO) were annealed significantly by administration of RGP in a dose-dependant manner. The histopathological examination of rat liver section was found to reinforce the biochemical observations significantly. It was observed that a substantial and dose-dependent reversal of DENA-diminished activity of antioxidant enzymes like SOD, CAT, GPx, GST and the reduced DENA-elevated level of LPO with a marked change. Any elevation in the levels of serum markers along with suppression of free radical formation by scavenging the hydroxyl radicals is significantly prevented by RGP. It also modulates the levels of LPO and perceptibly increases the endogenous antioxidant enzymes level in DENA-induced hepatocellular carcinogenesis. The findings suggest that RGP prevents hepatocellular carcinoma by suppressing the marked increase in the levels of serum marker enzymes, and suppresses the free radical by scavenging hydroxyl radicals.     

Cytoprotective effects of carvedilol against oxygen free radical generation in rat liver

The protective effects of carvedilol, an antihypertensive agent, against oxidative injury caused by acetaminophen were studied in rat liver. Male Wistar rats (250 +/- 30 g) were pre-treated with carvedilol (3.6 mg/kg, p.o.) for 10 days and on the 11th day received an overdose of acetaminophen (800 mg/kg, p.o.). Four hours after acetaminophen administration, blood was collected to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). After that, rats were killed and the livers were excised to determine reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl protein contents, and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST), and also the DNA damage index. Acetaminophen significantly increased the levels of TBARS, the DNA damage and SOD, AST and ALT activities. Carvedilol was able to prevent lipid peroxidation, protein carbonilation and DNA fragmentation caused by acetaminophen. Moreover, this drug prevented increases in SOD, AST and ALT activities. These results show that carvedilol exerts cytoprotective effects against oxidative injury caused by acetaminophen in rat liver. These effects are probably related to the O2*- scavenging property of carvedilol or its metabolites.     

Glutathione redox system,GSH-Px activity and lipid peroxidation (LPO) levels in tadpoles of R.r.ridibunda and B.viridis

Total glutathione (t-GSH), reduced glutathione (GSH), glutathione disulphide (GSSG) levels, t-GSH/GSSG ratio, glutathione peroxidase (GSH-Px) activity and lipid peroxidation (LPO) levels were investigated during the development period of a predominantly aquatic amphibian R.r.ridibunda and a predominantly terrestrial amphibian B. viridis. While t-GSH and GSH showed a similar trend, GSSG concentration increased significantly (p<0.05) during the larval stages in R.r.ridibunda larvae. In contrast to R.r.ridibunda larvae, there was no significant (p>0.05) change between 1 and 5 weeks in the t-GSH and GSH concentrations of B. viridis. t-GSH and GSH concentrations of B. viridis larvae became sharply elevated after the fifth week, GSSG levels increased 3.25-fold during the metamorphosis. The t-GSH/GSSG ratio fluctuated and the lowest t-GSH/GSSG ratios were observed at the third week for both species. GSH-Px activities for both species increased significantly (p<0.05) during the growing period. The highest GSH-Px activities in R.r.ridibunda and B.viridis were observed at the eighth week and they were 3.45 +/- 0.17 and 4.1 +/- 0.21 IU mg(-1), respectively. The membrane LPO levels in the R.r.ridibunda and B. viridis tadpoles significantly (p<0.001) decreased from 206 +/- 10.3 to 146 +/- 7.3 and from 198 +/- 9.9 to 23 +/- 1.15 nmol MDA g(-1) w.w., respectively.     

Levetiracetam protects against kainic acid-induced toxicity

We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) induced neurotoxicity. Brain injury was induced by intraperitoneal administration of KA (10 mg/kg). Sham brain injury rats were used as controls. Animals were randomized to receive either LVT (50 mg/kg) or its vehicle (1 ml/kg) 30 min. before KA administration. Animals were sacrificed 6 hours after KA injection to measure brain malonildialdehyde (MDA), glutathione levels (GSH) and the mRNA for interleukin-1beta (IL-1beta) in the cortex and in the diencephalon. Behavioral changes were also monitored. Intraperitoneal administration of LVT decreased significantly MDA in the cortex (KA + vehicle = 0.25 +/- 0.03 nmol/mg protein; KA + LVT = 0.13 +/- 0.01 nmol/mg protein; P < 0.005), and in the diencephalons (KA + vehicle = 1,01 +/- 0.2 nmol/mg protein; KA + LVT = 0,33 +/- 0,08 nmol/mg protein; P < 0.005), prevented the brain loss of GSH in both cortex (KA + vehicle = 5 +/- 1 micromol/g protein; KA + LVT = 15 +/- 2 micromol/g protein; P < 0.005) and diencephalons (KA + vehicle = 9 +/- 0.8 micromol/g protein; KA + LVT = 13 +/- 0.3 micromol/g protein; P < 0.05), reduced brain IL-1beta mRNA and markedly controlled seizures. Histological analysis showed a reduction of cell damage in LVT treated samples. The present data indicate that LVT displays neuro-protective effects against KA induced brain toxicity and suggest that these effects are mediated, at least in part, by inhibition of lipid peroxidation.     

Protective effect of resveratrol and vitamin E against ethanol-induced oxidative damage in mice: biochemical and immunological basis

The metabolism of ethanol gives rise to the generation of excess amounts of reactive oxygen species and is also associated with immune dysfunction. We examined the efficacy of resveratrol and vitamin E on the immunomodulatory activity and vascular function in mice with liver abnormalities induced by chronic ethanol consumption by measuring the protein, liver-specific transaminase enzymes, antioxidant enzymes and non-enzymes such as reduced glutathione (GSH) content, thiobarbituric acid reactive substance (TBARS) level, nitrite level, and activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and cytokines such as interleukin (IL)-2, IL-4, IL-10, tumor necrosis factor (TNF)-alpha, gamma interferon (IFN-gamma), vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)-beta1 in mice blood. Ethanol (1.6 g/kg body wt/day) exposure for 12 wks significantly increased TBARS and nitrite levels and GST activity, and significantly decreased GSH content and the activities of SOD, CAT, GR and GPx in whole blood hemolyzate of 8-10 wks-old male BALB/c mice (weighing 20-30 g). Ethanol exposure also elevated the activities of transaminase enzymes (AST and ALT), IL-10, TNF-alpha, IFN-gamma, VEGF-A and TGF-beta1, while decreasing the albumin concentration and IL-4 activity in the serum. Both resveratrol (5 mg kg(-1) day(-1)) and vitamin E (80 mg kg(-1) day(-1)) treatment significantly reduced AST, ALT, GST, IL-10, TNF-alpha, IFN-gamma, VEGF-A and TGF-beta1 activities and levels of TBARS and nitrite, and elevated albumin content, GSH level and activities of SOD, CAT, GR and GPx, compared to ethanol-treated group. Thus, results from the study demonstrated that both resveratrol (5 mg kg(-1) day(-1)) and vitamin E (80 mg kg(-1) day(-1)) can effectively ameliorate ethanol (1.6 g kg(-1) day(-1))-induced oxidative challenges, immunomodulatory activity and angiogenesis processes.     

Effects of oxidative stress on the expression of antioxidative defense enzymes in spontaneously hypertensive rat hearts

Little is known concerning the effect of oxidative stress on the expression of antioxidative enzymes in the decompensated cardiac hypertrophy of spontaneously hypertensive rats (SHR), considered as a model of dilative cardiomyopathy in man. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) were characterized in isolated perfused hearts of 18 month old SHR and the age-matched normotensive control Wistar-Kyoto (WKY) rats, before and after 30 min infusion of 25 microM H(2)O(2). After infusion of H(2)O(2), aortic flow decreased in WKY from 26.2 +/- 2.2 to 16.0 +/- 0.8 ml/min (p <.05) but not in SHR (18.2 +/- 1.9 vs. 20.7 +/- 2.2 ml/min). This protection was related to the higher myocardial activities of GPx, MnSOD and CuZnSOD in SHR, compared with those of the WKY group. Although total SOD activity in the SHR fell after H(2)O(2) exposure (to 1.81 +/- 0.13 from 3.56 +/- 0.49 U/mg of protein), catalase activity increased (to 2.46 +/- 0.34 from 1.56 +/- 0.29 k min(-1)mg(-1)protein), compared with the pre-infusion period (p <.05 in each case). In additional studies, hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. The results obtained in ischemic/reperfused hearts show the same changes in enzyme activities measured as it was observed in H(2)O(2) perfused hearts, indicating that oxidative stress is independent of the way it was induced. The higher catalase activity derived from elevated mRNA synthesis. The antioxidative system in dilative cardiomyopathic hearts of SHR is induced, probably due to episodes of oxidative stress, during the process of decompensation. This conditioning of the antioxidative potential may help overcome acute stress situations caused by reactive oxygen species in the failing myocardium.     

Acorus calamus extracts and nickel chloride: prevention of oxidative damage and hyperproliferation response in rat kidney

Nickel, a major environmental pollutant, is known for its clastogenic, toxic, and carcinogenic potential. In this article, we report the effect of Acorus calamus on nickel chloride (NiCl2)-induced renal oxidative stress, toxicity, and cell proliferation response in male Wistar rats. NiCl2 (250 micromol/kg body weight/mL) enhanced reduced renal glutathione content (GSH), glutathione- S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO), H2O2 generation, blood urea nitrogen (BUN), and serum creatinine with a concomitant decrease in the activity of glutathione peroxidase (GPx) (p < 0.001). NiCl2 administration also dose-dependently induced the renal ornithine decarboxylase (ODC) activity several-fold as compared to salinetreated control rats. Similarly, renal DNA synthesis, which is measured in terms of [3H] thymidine incorporation in DNA, was elevated following NiCl2 treatment. Prophylactic treatment of rats with A. calamus (100 and 200 mg/kg body weight po) daily for 1 wk resulted in the diminution of NiCl2- mediated damage, as evident from the downregulation of glutathione content, GST, GR, LPO, H2O2 generation, BUN, serum creatinine, DNA synthesis (p < 0.001), and ODC activity (p < 0.01) with concomitant restoration of GPx activity. These results clearly demonstrate the role of oxidative stress and its relation to renal disfunctioning and suggest a protective effect of A. calamus on NiCl2-induced nephrotoxicity in a rat experimental model.     

The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid.

The antiulcerogenic effect of diffractaic acid (DA) isolated from Usnea longissima, a lichen species, on indomethacin (IND)-induced gastric lesions was investigated in rats. Administration of 25, 50, 100 and 200 mg/kg doses of DA and ranitidine (RAN) (50 mg/kg dose) reduced the gastric lesions by 43.5%, 52.9%, 91.4%, 96.7% and 72.7%, respectively. It is known that oxidative stress leads to tissue injury in organisms. Thus, in all treated groups of rats, the in vivo activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were evaluated. IND caused oxidative stress, which resulted in LPO in tissues, by decreasing the levels of GPx, SOD and GSH as compared to healthy rats. In contrast to IND, the administration of DA and RAN showed a significant decrease in LPO level and an increase in tissue SOD, GPx and GSH levels. However, while CAT activity was significantly increased by the administration of IND, the administration of DA and RAN decreased CAT activity. The administration of IND also increased the myeloperoxidase (MPx) activity, which shows neutrophil infiltration into the gastric mucosal tissues. In contrast to IND, the administration of DA and RAN decreased MPx activity. The changes in activities of gastric mucosal nitric oxide synthases (NOS) throughout the development of gastric mucosal damage induced by IND were also studied. A decrease in constitutive NOS (cNOS) activity and an increase in inducible NOS (iNOS) activity were determined in gastric damaged tissues induced by IND. The administration of DA (100 mg/kg dose) and RAN reversed the activities of iNOS and cNOS. These results suggest that the gastroprotective effect of DA can be attributed to its enhancing effects on antioxidant defense systems as well as reducing effects of neutrophil infiltration.     

Thiamine deficiency induces oxidative stress in brain mitochondria of Mus musculus

The present investigation evaluates the changes in the levels of antioxidant enzymes, lipid peroxidation (LPO), and protein carbonyl content (PCC) in brain mitochondria following thiamine deficiency (TD). The study was carried out on Mus musculus allocated into three groups, namely control and thiamine-deficient group for 8 (TD 8) and 10 (TD 10) days. The LPO was measured in terms of reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured biochemically. A significant increase in the TBARS (p?<?0.0001) and PCC (p?<?0.001) levels in group II (TD 8) and group III (TD 10) animals was observed in comparison to controls. The GSH levels were found to be reduced in both the treated groups compared to the control. A significant reduction in the activities of SOD was also observed in group II (p?<?0.01) and group III (p?<?0.0001) animals in comparison to the control. Enzymatic activities of CAT (p?<?0.001) and GPx (p?<?0.05) were found to be significantly reduced in group III (TD 10) in comparison to the control. In conclusion, reduction in the activities of antioxidant enzymes as well as an increase in LPO and PCC following TD implies oxidative stress in brain mitochondria that may further leads to neurodegeneration.