Antioxidant activity of fluoxetine: Studies in mice melanoma model

In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of C57BL/6 mice were studied using a melanoma experimental model. After a 14‐day treatment with fluoxetine (10 mg kg^?1 day^?1, i.p.), the endogenous antioxidant non‐enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug‐protective effect against the melanoma‐induced oxidative changes (increased LP and decreased total glutathione (GSH)‐level, as well as antioxidant enzyme activities) in spleen was observed. Fluoxetine dose‐dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Taken together, the present results suggest that fluoxetine, acting as antioxidant, prevents from melanoma‐induced oxidative changes in mice spleen. Copyright © 2010 John Wiley & Sons, Ltd.     

In vivo effects of pentoxifylline on enzyme and non-enzyme antioxidant levels in rat liver after carrageenan-induced paw inflammation

The present study aimed to investigate the effects of pentoxifylline (PTX) on the carrageenan (CG)-induced paw oedema and on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver, 4 and 24 h after CG injection. PTX (50 mg kg(-1) , i.p.), administered 30 min before CG, decreased the paw oedema, 2-4 h after CG administration. The drug protected CG-induced decrease of glutathione (non-enzyme antioxidant) and had no effect on CG-unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose-6-phosphate dehydrogenase (enzyme, important for the activity of GSH-conjugated antioxidant enzymes). The drug showed a good antioxidant capacity in chemical systems, generating reactive oxygen species. The present results suggest that the antioxidant activity of PTX might contribute to its beneficial effects in liver injuries.     

The effects of vitamins and selenium mixture against brain tissue induced by d‐galactosamine

Brain damage is a major complication of fulminant hepatic failure. d ‐Galactosamine (d ‐GalN)‐induced liver toxicity causes damage to brain. The effects of vitamins and selenium mixture against d ‐GalN stimulated brain injury were investigated in this study. Sprague‐Dawley female rats aged 2.0‐2.5 months were used for the study. The rats were divided into four categories. A 0.9% NaCl solution was intraperitoneally given to the experimental rats in the first group. Using gavage technique, the second group of animals were subjected to a formulation consisting of 100 mg·kg^?1·day^?1 vitamin C, 15 mg·kg^?1·day^?1 of β‐carotene, 100 mg·kg^?1·day^?1 of α‐tocopherol in addition to 0.2 mg·kg^?1·day^?1 of sodium selenate for 3 days. The third group was given a single dose of d ‐GalN hydrochloride at the concentration of 500 mg·kg^?1 through a saline injection. The final group was given similar concentrations of both the antioxidant combination and d ‐GalN. Tissue samples were collected under ether anesthesia. The rats treated with d ‐GalN showed brain damage; increased myeloperoxidase, catalase, glutathione peroxidase, glutathione‐S‐transferase, lactate dehydrogenase, and superoxide dismutase activities; and decreased glutathione levels. Treatment with vitamins and selenium combination resulted in alleviation of these alterations in the rats. These findings suggest that administration of the vitamins and selenium combination suppresses oxidative stress and protects brain cells from injury induced by d ‐GalN.     

Further pharmacological evidence of the neuroprotective effect of catalpol from Rehmannia glutinosa

We have previously evaluated the neuroprotective effect of catalpol on aging mice induced by d-galactose, in which catalpol treatment ameliorated cognition deficits and attenuated oxidative damage in mice brain. To thoroughly elucidate the anti-aging effects of catalpol, the liver and spleen antioxidative systems and energy metabolism in senescent mice induced by d-galactose have been studied. Except control group, mice were subcutaneously injected with d-galactose (150 mg kg⁻¹ body weight) for 6 weeks. Meanwhile, drug group mice were treated with catalpol (2.5, 5, 10 mg kg⁻¹ body weight) and piracetam (300 mg kg⁻¹ body weight) for the last 2 weeks. The activities of endogenous antioxidants and the level of glutathione (GSH) and lipid peroxide in the liver and spleen were assayed. Compared to control group, model group mice had significantly lower spleen index (spleen weight/body weight), lower level of GSH, lower activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), higher level of malondialdehyde (MDA) in the liver and spleen. However, catalpol administration markedly reversed these effects of senescence induced by d-galactose. Simultaneously, catalpol noticeably elevated the decreased activities of lactate dehydrogenase (LDH), glutamine synthetase (GS), Na⁺-K⁺-ATPase, Ca²⁺-Mg²⁺-ATPase and decreased the elevated activity of creatine kinase (CK) in mice liver or spleen. These results implied that the anti-aging effects of catalpol were achieved at least partly by promoting endogenous antioxidant enzyme activities and normalizing energy disturbance. Catalpol may be a potential anti-aging agent and worth testing for further preclinical study aimed for senescence or neurodegenerative diseases such as Alzheimer's and Parkinson's diseases.     

Diethylstilbestrol Attenuates Antioxidant Activities in Testis from Male Mice

It has been reported that acute exposure to diethylstilbestrol (DES) induces apoptosis in the testis, and antioxidants play a role in preventing DES-induced tissue damage. In this study, the effect of chronic exposure to DES on the antioxidants was examined in the testis and liver. Eight-week old male ICR mice were treated subcutaneously with various doses of DES for 20 days. Morphologically apparent apoptotic changes, 4-hydroxy-2-nonenal-positive cells and TUNEL-positive DNA-fragmentation, were demonstrated in the testis, but were minimal in the liver. Activities of antioxidants such as glutathione (GSH) peroxidase and GSH S -transferase decreased in both the liver and testis. The activity of Mn-superoxide dismutase (SOD) decreased in the liver but increased in the testis. The activity of Cu, Zn-SOD decreased in the liver but was unchanged in the testis. On Western and Northern blots, gamma-glutamylcysteine synthetase ( &#110 -GCS), a rate limiting enzyme of GSH synthesis, was increased in the liver dependent on the dose of DES. However, the expression of &#110 -GCS was reduced in the testis. Since quinones, metabolites of DES, generate reactive oxygen species, which damage DNA, antioxidants are important to prevent the damage. The data suggest that antioxidant activities are impaired by DES, and the levels of GSH are related to DES-induced apoptosis in the testis.     

Diethylstilbestrol attenuates antioxidant activities in testis from male mice

It has been reported that acute exposure to diethylstilbestrol (DES) induces apoptosis in the testis, and antioxidants play a role in preventing DES-induced tissue damage. In this study, the effect of chronic exposure to DES on the antioxidants was examined in the testis and liver. Eight-week old male ICR mice were treated subcutaneously with various doses of DES for 20 days. Morphologically apparent apoptotic changes, 4-hydroxy-2-nonenal-positive cells and TUNEL-positive DNA-fragmentation, were demonstrated in the testis, but were minimal in the liver. Activities of antioxidants such as glutathione (GSH) peroxidase and GSH S -transferase decreased in both the liver and testis. The activity of Mn-superoxide dismutase (SOD) decreased in the liver but increased in the testis. The activity of Cu, Zn-SOD decreased in the liver but was unchanged in the testis. On Western and Northern blots, gamma-glutamylcysteine synthetase ( γ-GCS), a rate limiting enzyme of GSH synthesis, was increased in the liver dependent on the dose of DES. However, the expression of γ-GCS was reduced in the testis. Since quinones, metabolites of DES, generate reactive oxygen species, which damage DNA, antioxidants are important to prevent the damage. The data suggest that antioxidant activities are impaired by DES, and the levels of GSH are related to DES-induced apoptosis in the testis.     

In vivo effects of N/OFQ(1–13)NH2 and its structural analogue [ORN9]N/OFQ(1–13)NH2 on carrageenan-induced inflammation: rat-paw oedema and antioxidant status

The effects of nociceptin(1–13)NH₂ (N/OFQ(1–13)NH₂) and its structural analogue [Orn⁹]N/OFQ(1–13)NH₂ on acute carrageenan (CG)-induced peripheral inflammation and paw antioxidant status were studied. CG was injected intraplantarly in the right hind paw of rats and the volume of the inflamed paw was measured each 30 min for a period of 4h. When administered simultaneously with CG, N/OFQ(1–13)NH₂ decreased the paw volume, whereas if injected 15 min before CG it had no effect. [Orn₉]N/OFQ(1–13)NH₂ produced the opposite effects at the same time-intervals of its administration. We also investigated whether these neuropeptides influence CG-induced changes in cell antioxidant system, especially at the 4th hour of CG administration. CG alone decreased the glutathione level and superoxide dismutase activity, as measured in post-nuclear homogenate of the inflamed paw. However, CG injection increased glutathione peroxidase and glucose-6-phospate dehydrogenase activities, while the activity of glutathione reductase was unchanged. The peptides themselves did not change all measured parameters. Moreover, neither N/OFQ(1–13)NH₂ nor [Orn⁹]N/OFQ(1–13)NH₂ modified CG-induced changes in the antioxidant status, regardless of the time of their injection (simultaneously or 15 min before CG). The present results suggest that N/OFQ(1–13)NH₂ and [Orn⁹]N/OFQ(1–13)NH₂ most likely affect the neuronal inflammation, rather than act as pro- or antioxidants.     

Omega 3 chronic supplementation attenuates myocardial ischaemia‐reperfusion injury through reinforcement of antioxidant defense system in rats

Currently, controversial clinical data about the protective effects in the consumption of n‐3 polyunsaturated fatty acids (PUFAs) in ischaemic heart diseases exist. Improved myocardial resistance to ischaemia‐reperfusion (IR) injury results in non‐lethal myocardial infarction, which is a relevant factor in the myocardial function. We hypothesized that chronic supplementation with PUFAs reduced infarct size (IS) and induced an improvement on oxidative stress‐related parameters in IR model. Rats were supplemented with two doses of PUFAs D1 (n = 7) (0.6 g kg^?1 d^?1) and D2 (n = 7) (1.2 g kg^?1 d^?1) for 8 weeks. Control group (n = 7) received only standard diet. In ex vivo model, all rat hearts were subjected to 30 min of global ischaemia followed by 120 min of reperfusion. The IS and left ventricular function were assessed. Lipid peroxidation, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio and antioxidant enzyme activity were measured in the whole heart. The results show a reduction in IS in a dose‐dependent manner with PUFAs D1 (30.6%) and D2 (48.5%) and higher values of left ventricular developed pressure, at the end of the reperfusion, for each dose, respectively (p < 0.05). The two PUFAs groups showed higher values of GSH/GSSG ratio and lipid peroxidation, and higher values of activity of antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase at basal condition (p < 0.05). At the end of reperfusion, the GSH/GSSG ratio and antioxidants enzyme activity did not show a significant drop in their values (p > 0.05). These findings suggested that the supplementation with PUFAs induces cardioprotection against IR injury, associated with reinforcement of the antioxidant defense system. Copyright © 2013 John Wiley & Sons, Ltd.     

Investigation of unmatured hematopoietic cell migration in a mouse model

The objective of this work was to examine the migration of transplanted bone marrow hematopoietic lin⁻ cell population using the BALB/c mouse contact hypersensitivity model in vivo and to determine the time point at which they reach the site of injury (paw edema) as well as other undamaged organs, such as liver and spleen. Female BALB/c mice with induced contact hypersensitivity reaction were intravenously injected with 1×10⁶ cells/mouse lin⁻ cells, labeled with PKH67. The presence of lin⁻ stained cells in mouse tissue sections was evaluated by fluorescent microscopy. After one hour, the labeled cells were found in mice paw edema and liver, and after 4 hours in spleen tissue. Migrated hematopoietic lin⁻ cells remained in liver tissue for 48 h, and in spleen and paw edema at least for 72 h. Migrated stained cells in untreated paw were not found. The results prove that bone marrow unmatured hematopoietic cells are first found in paw edema, where they participate in the inhibition of tissue inflammation; these cells subsequently migrate to the liver and are found in the spleen shortly afterwards.     

Pyrroloquinoline quinone ameliorates l‐thyroxine‐induced hyperthyroidism and associated problems in rats

Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this study, we have evaluated its hitherto unknown role in l ‐thyroxin (L‐T₄)‐induced hyperthyroidism considering laboratory rat as a model. Alterations in the serum concentration of thyroxin (T₄) and triiodothyronine (T₃); lipid peroxidation (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants such as superoxide dismutase, catalase and glutathione and in serum total cholesterol, high‐density lipoprotien, triglycerides, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea were evaluated. Administration of l ‐T₄ (500‐µg kg^?1 body weight) enhanced not only the serum T₃ and T₄ levels but also the tissue LPO, serum SGOT, SGPT and urea with a parallel decrease in the levels of antioxidants and serum lipids. However, on simultaneous administration of PQQ (5 mg kg^?1 for 6 days), all these adverse effects were ameliorated, indicating the potential of PQQ in the amelioration of hyperthyroidism and associated problems. Possibly, the curative effects were mediated through inhibition of oxidative stress. We suggest that PQQ may be considered for therapeutic use for hyperthyroidism after dose standardization. Copyright © 2014 John Wiley & Sons, Ltd.     

Prophylactic Role of a Herbomineral Drug “Thamira Parpam” Against Cysteamine-Induced Oxidative Stress in Liver and Duodenum of Rats

Copper is known as Gunma Kaalan in Siddha literature, which means that the drug is effective for healing ulcers. The herbomineral drug “Thamira parpam” is prepared by calcining the purified copper foils with rock salt, lime juice, bracteated birth wort juice, and Alangium root decoction according to Siddha medicine. Our study investigated the possible role of Thamira parpam (TP) in the management of cysteamine-induced duodenal ulcers. Cysteamine (400 mg kg^?1?body weight^?1, two doses at 4 h interval) orally given to rats resulted in high ulcer index, increased TBARS with concomitant depletion of antioxidants such as superoxide dismutase, glutathione, glutathione peroxidase, and inflammatory markers cathepsin D, and myeloperoxidase (p?<?0.01). Herbomineral drug TP (0.5, 1, and 2 mg/kg, p.o.) challenged with cysteamine attenuated the elevation of TBARS and imbalance of antioxidants. In the increases in liver inflammatory markers, tissue histopathology changes were not severe in TP treatment. Positive control omeprazole (25 mg/kg, body weight, orally) showed considerable protection against anomaly in biochemical parameters and tissue histology. Hence, our results indicate that the attenuation of oxidative stress by the herbomineral drug in experimentally induced damage to liver and duodenum of rats could be mediated by free radical quenching property.     

Vitamin C, resveratrol and lipoic acid actions on isolated rat liver mitochondria: all antioxidants but different

Modulating mitochondrial antioxidant status is a nutritional issue of great interest in the treatment or prevention of several oxidative stress related diseases such as obesity. Thus, the aim of the present study was to analyze the effects of three antioxidants on hepatic mitochondrial function and antioxidant status. Isolated rat liver mitochondria were incubated with vitamin C, resveratrol and lipoic acid. The activity of antioxidant enzymes (manganese superoxide dismutase and glutathione peroxidase), ROS generation and respiratory parameters (RCR, P/O ratio and respiratory states) were measured. Vitamin C influenced mitochondrial function by decreasing of ROS generation (P < 0.0001), by stimulating the activity of manganese superoxide dismutase (197.60 ± 35.99%; P < 0.001) as well as glutathione peroxidase (15.70 ± 5.76%; P < 0.05) and by altering the activity of the electron transport chain, mainly by decreasing the P/O ratio (P < 0.05). Resveratrol induced a significant increase in manganese superoxide dismutase activity (160 ± 11.78%; P < 0.0001) and a decrease in ROS generation (P < 0.05 to P < 0.0001). By contrast, lipoic acid inhibited glutathione peroxidase activity (16.48 ± 3.27%; P < 0.05) and induced the uncoupling of the electron transport chain (P < 0.01). Moreover, this antioxidant induced a strong decrease in the P/O ratio (P < 0.05 to P < 0.0001). In conclusion, our results suggest that the three tested antioxidants produced direct effects on mitochondrial function, although the magnitude and intensity of these actions were significantly different, which may have implications when administrated as antioxidants.     

Antioxidant protection by β‐selenoamines against thioacetamide‐induced oxidative stress and hepatotoxicity in mice

Thioacetamide (TAA) is a hepatotoxin that rapidly triggers the necrotic process and oxidative stress in the liver. Nevertheless, organic selenium compounds, such as β‐selenoamines, can be used as pharmacological agents to diminish the oxidative damage. Thus, the aim of this study was to investigate the protective effect of the antioxidant β‐selenoamines on TAA‐induced oxidative stress in mice. Here, we observed that a single intraperitoneal injection of TAA (200 mg/kg) dramatically elevated some parameters of oxidative stress, such as lipid peroxidation and reactive oxygen species (ROS) production, as well as depleted cellular antioxidant defenses. In addition, TAA‐induced edema and morphological changes in the liver, which correlate with high serum aspartate and alanine aminotransferase enzyme activities, and a decrease in cell viability. Conversely, a significant reduction in liver lipid peroxidation, ROS production, and edema was observed in animals that received an intraperitoneal injection of β‐selenoamines (15.6 mg/kg) 1 h after TAA administration.     

Protective effects of antioxidant combination against D‐galactosamine‐induced kidney injury in rats

The protective effects of an antioxidant combination in kidney injury induced by the injection of D‐galactosamine (D‐GaIN) were examined in the present study. Sprague Dawley female rats were used and divided into four groups as follows: (1) animals injected physiological saline solution, intraperitoneally, (2) animals treated with the combination of ascorbic acid (100 mg kg^?1 day^?1), β‐carotene (15 mg kg^?1 day^?1), α‐tocopherol (100 mg kg^?1 day^?1), and sodium selenate (0.2 mg kg^?1 day^?1) for three days orally, (3) rats injected D‐GaIN (500 mg kg^?1) intraperitoneally as a single dose, and (4) animals treated with the antioxidant combination for three days, then injected D‐GaIN. The tissue and blood samples of animals were collected for morphological and biochemical evaluations. Histopathological injury in kidney tissues was observed together with a significant increase in tissue lipid peroxidation (LPO) level, myeloperoxidase (MPO), lactate dehydrogenase, catalase and superoxide dismutase (SOD) activities, and serum creatinine and urea levels, and a significant decrease in glutathione level and glutathione peroxidase activity in D‐GaIN injected rats. However, a decrease in the degenerative changes was detected in the kidney tissue of D‐GaIN + antioxidant group, and biochemical results showed reversed effects. In conclusion, it seems reasonable to conclude that the treatment of the antioxidant combination has a protective effect on D‐GaIN‐induced kidney injury of rats. Copyright © 2010 John Wiley & Sons, Ltd.     

Semecarpus anacardium nut extract promotes the antioxidant defence system and inhibits anaerobic metabolism during development of lymphoma

Antioxidants are substances that fight against ROS (reactive oxygen species) and protect the cells from their damaging effects. Production of ROS during cellular metabolism is balanced by their removal by antioxidants. Any condition leading to increased levels of ROS results in oxidative stress, which promotes a large number of human diseases, including cancer. Therefore antioxidants may be regarded as potential anticarcinogens, as they may slow down or prevent development of cancer by reducing oxidative stress. Fruits and vegetables are rich source of antioxidants. Moreover, a number of phytochemicals present in medicinal plants are known to possess antioxidant activity. Therefore the aim of the present study was to investigate antioxidant activity of the aqueous extract of nuts of the medicinal plant Semecarpus anacardium in AKR mouse liver during the development of lymphoma. Antioxidant action was monitored by the activities of antioxidant enzymes catalase, superoxide dismutase and glutathione transferase. The effect of S. anacardium was also studied by observing the activity of LDH (lactate dehydrogenase), an enzyme of anaerobic metabolism. LDH activity serves as a tumour marker. The activities of antioxidant enzymes decreased gradually as lymphoma developed in mouse. However, LDH activity increased progressively. Administration of the aqueous extract of S. anacardium to lymphoma-transplanted mouse led to an increase in the activities of antioxidant enzymes, whereas LDH activity decreased significantly, indicating a decrease in carcinogenesis. The aqueous extract was found to be more effective than doxorubicin, a classical anticarcinogenic drug, with respect to its action on antioxidant enzymes and LDH in the liver of mice with developing lymphomas.     

Montelukast abrogates prednisolone‐induced hepatic injury in rats: Modulation of mitochondrial dysfunction,oxidative/nitrosative stress,and apoptosis

The aim of this study was to investigate the protective effect of montelukast (MTK) against prednisolone‐induced hepatic injury in rats. Twenty‐eight male albino rats were categorized into four equal groups. Group I served as the control group; group II: rats orally received prednisolone (5 mg·kg^?1·d^?1) for 30 days; groups III and IV: rats orally received MTK at 10 and 20 mg·kg^?1·d^?1, respectively, simultaneously with prednisolone for 30 days. Serum liver enzymes, hepatic mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic markers were evaluated, and the results were confirmed by histopathological examination. MTK showed significant hepatic protection evidenced by alleviated histological lesion and improvement of mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic changes induced by prednisolone, with more profound protection in higher MTK dose (20 mg·kg^?1). In view of these findings, we can conclude that MTK may have hepatoprotective potential, beyond its therapeutic value for asthmatic patients during their course of corticosteroid therapy.     

Induced anti-oxidant activity in soybean alleviates oxidative stress under moderate boron toxicity

The effect of B toxicity on antioxidant responses of soybean (Glycine max) cv. Athow was investigated by growing plants for 43 days at 0.2 (control), 2 and 12 mg B kg^?1. At the end of the treatment period, shoot growth, lipid peroxidation level, the activities of antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POX), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR), and their isoenzymes in leaves were measured. Boron concentration in leaves was significantly increased by the increasing levels of B treatment from 43 to 522 mg kg^?1, and shoot dry matter was depressed at 12 mg B kg^?1. Significant increases in SOD, CAT, and APX activities were determined in leaves under 12 mg B kg^?1; however, GR activities were decreased while POX activity was unchanged. Increased enzymic antioxidant activity arose from a combination of newly formed isoenzymes and activation of existing isoenzymes. By contrast, SOD and GR activities were decreased by 2 mg B kg^?1 concentration as compared to the control groups while POX activity was increased and the activity of CAT did not change. Malondialdehyde content increased under 2 mg B kg^?1 but decreased under 12 mg B kg^?1. These results suggest that higher antioxidant activity observed under 12 than at 2 mg B kg^?1 provided higher free radical-scavenging capacity, and thus a lower level of lipid peroxidation in Athow. While the induction of increased antioxidant activity was related to internal boron levels, the signaling and coordination of responses remain unclear.     

Erdosteine modulates radiocontrast‐induced hepatotoxicity in rat

It has been suggested that reactive oxygen species (ROS) plays an important role in radio contrast media (RCM)‐induced ischemia reperfusion tissue injury although antioxidants may have protective effects on the injury. We investigated the effects of erdosteine as an antioxidant agent on RCM‐induced liver toxicity in rats by evaluation of lipid peroxidation (as TBARS), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GSH‐Px) values and histological evaluation. Twenty‐one rats were equally divided into three groups as follows: control, RCM, and RCM plus erdosteine. RCM was intraperitoneally administered for 1 day. Erdosteine was administered orally for 2 days after RCM administration. Liver samples were taken from the rats and they homogenized in a motor‐driven tissue homogenizer. TBARS levels were significantly (p < 0.005) higher in RCM group than in control although SOD activities significantly (p < 0.05) decreased in RCM group. TBARS levels were lower in RCM plus erdosteine group than in control although SOD activity and GSH level increased (p < 0.05) in liver as compared to RCM alone. Erdosteine showed also histopathological protection (p < 0.0001) against RCM induced hepatotoxicity. GSH‐Px and CAT activities were not statistically changed by the erdosteine. According to our results, it can be concluded that radiocontrast media can induce oxidative stress in liver as suggested by previous studies. Erdosteine seems to be protective agent on the radiocontrast media‐induced liver toxicity by inhibiting the production of ROS via the enzymatic antioxidant system. Copyright © 2009 John Wiley & Sons, Ltd.     

Antioxidant activity of Terminalia arjuna bark extract on N-nitrosodiethylamine induced hepatocellular carcinoma in rats

Role of oxidative stress and Na⁺,K⁺-ATPase in the cytotoxicity of hexachlorocyclohexane (HCH) on Ehrlich Ascites tumor (EAT) cells has been studied. HCH caused dose dependent cell death as measured by trypan blue exclusion and lactate dehydrogenase (LDH) leakage from the cells. HCH induced oxidative stress in EAT cells which was characterized by glutathione depletion, lipid peroxidation (LPO), reactive oxygen species (ROS) production and inhibition of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT). Protective effect of antioxidants on HCH induced oxidative stress was assessed, among the antioxidants used only quercetin inhibited HCH-induced LPO and ROS production as well as cell death whereas α -tocopherol, ascorbic acid and BHA inhibited LPO but not cell death. Inhibition of membrane bound Na⁺,K⁺-ATPase was a characteristic feature of HCH cytotoxicity in EAT cells. Experimental evidence indicates that HCH-induced cell death involves oxidative stress due to ROS production and membrane perturbation in EAT cells.