Pleurotus ostreatus, an oyster mushroom, decreases the oxidative stress induced by carbon tetrachloride in rat kidneys, heart and brain

The present work is aimed at evaluating the protective effect of the oyster mushroom, Pleurotus ostreatus on carbon tetrachloride (CCl4)-induced toxicity in male Wistar rats. Significantly elevated mean levels (p<0.05) of malondialdehyde (MDA) and lowered mean levels (p<0.01) of reduced glutathione (GSH), vitamins C and E (p<0.05) were observed in kidneys, heart and brain of rats exposed to CCl4, when compared to values in normal rats. Quantitative and qualitative analysis of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (Gpx) and glutathione-S-transferase (GST) revealed lower activities of these antioxidant enzymes in the kidneys, heart and brain of rats exposed to CCl4. When the extract of P. ostreatus was used to treat rats with CCl4-induced toxicity, it lowered the mean level of MDA, elevated the mean levels of GSH and of vitamins C and E and enhanced the mean activities of CAT, SOD, Gpx and GST so that the values of most of these parameters did not differ significantly from those of normal rats. Histopathological studies confirmed the toxic effects of CCl4 on other organs such as kidneys, heart and brain and also tissue protective effect of the extract of P. ostreatus. These results suggest that an extract of P. ostreatus is able to alleviate the oxidative damage caused by CCl4 in the kidneys, heart and brain of Wistar rats.     

Melatonin protects the heart, lungs and kidneys from oxidative stress under intermittent hypobaric hypoxia in rats

Melatonin (N-acetyl-5-methoxytryptamine) is the main secretory product of the pineal gland in all mammals including humans, but it is also produced in other organs. It has been previously demonstrated to be a powerful organ-protective substance under oxidative stress conditions. The aim of this study was to evaluate the protective effect of melatonin in several organs such as heart, lung, kidney, and of the reproductive system, such as testis and epididymis in animals exposed to intermittent hypobaric hypoxia and therefore exposed to oxidative stress and analyzed by lipid peroxidation. Ten-week-old male Wistar rats were divided into 6 groups for 96 hours during 32 days under: 1) Normobaric conditions, 2) plus physiologic solution, 3) plus melatonin, 4) intermittent hypobaric hypoxia, 5 plus physiologic solution and 6) plus melatonin. The animals were injected with melatonin (10 mg/kg body weight) at an interval of 96 hours during 32 days. Results indicated that melatonin decreased lipid peroxidation in heart, kidneys and lung under intermittent hypobaric hypoxia conditions. However, it did not exhibit any protective effect in liver, testis, epididymis and sperm count.     

TNF-alpha blockade decreases oxidative stress in the paraventricular nucleus and attenuates sympathoexcitation in heart failure rats

Oxidative stress plays an important role in the pathophysiology of cardiovascular disease. Recent evidence suggests that cytokines induce oxidative stress and contribute to cardiac dysfunction. In this study, we investigated whether increased circulating and tissue levels of tumor necrosis factor (TNF)-alpha in congestive heart failure (CHF) modulate the expression of NAD(P)H oxidase subunits, Nox2 and its isoforms, in the paraventricular nucleus (PVN) of the hypothalamus and contribute to exaggerated sympathetic drive in CHF. Heart failure was induced in Sprague-Dawly rats by coronary artery ligation and was confirmed using echocardiography. Pentoxifylline (PTX) was used to block the production of cytokines for a period of 5 wk. CHF induced a significant increase in the production of reactive oxygen species (ROS) in the left ventricle (LV) and in the PVN. The mRNA and protein expression of TNF-alpha, Nox1, Nox2, and Nox4 was significantly increased in the LV and PVN of CHF rats. CHF also decreased ejection fraction, increased Tei index, and increased circulating catecholamines (epinephrine and norepinephrine) and renal sympathetic activity (RSNA). In contrast, treatment with PTX in CHF rats completely blocked oxidative stress and decreased the production of TNF-alpha and Nox2 isoforms both in the LV and PVN. PTX treatment also decreased catecholamines and RSNA and prevented further decrease in cardiac function. In summary, TNF-alpha blockade attenuates ROS and sympathoexcitation in CHF. This study unveils new mechanisms by which cytokines play a role in the pathogenesis of CHF, thus underscoring the importance of targeting cytokines in heart failure.     

Circaannual changes in antioxidants and oxidative stress in the heart and liver in rats

Reactive oxygen species are formed in physiological and pathological conditions in mammalian tissues. Because of their high reactivity, they may interact with biomolecules, inducing oxidative injury. Increases in lipid peroxidation can result in oxidative damage to cellular membranes. Protection against oxidative damage is provided by enzymatic and non-enzymatic antioxidant defenses. Antioxidant enzyme activities and lipid peroxidation, as an index of oxidative stress injury, were evaluated in different seasons over one year in the heart and liver of rats, maintained on a 12 h light and dark cycle. Glutathione peroxidase and catalase activities, in both tissues, were maximal in the summer season. Lipid peroxidation in the heart was maximal in the spring as compared to the other seasons and it did not vary in the liver during the year. These findings suggest that any study of antioxidants or oxidative stress must take into account such seasonal variations for a more precise analysis of changes due to any pathological condition.     

The antioxidant effect of Aronia melanocarpa extract in rats oxidative stress induced by cisplatin administration

BackgroundThe reactive oxygen species generated by numerous xenobiotic substances has as consequences the impairment of different organs normal function. Many plants pose antioxidant activity to counteract oxidative stress, among them being the chokeberry (Aronia melanocarpa). The purpose of present study was to determine if the use of A. melanocarpa extract can counteract the oxidative stress induced by cisplatin administration in rats.Material and methodsThe study was made on forty Wistar rats divided in four groups as follows: C (control): receiving i.p. 1 mL of saline solution; E1: receiving cisplatin 20 mg/kg bw, i.p.; E2: receiving cisplatin 20 mg/kg bw, i.p and A. melanocarpa berry 6 % aqueous extract as drinking water, and CB (control blank): i.p 1 mL saline solution and A. melanocarpa 6 % aqueous extract for four weeks. Results. Administration of Cisplatin was followed by the increase of serum superoxide dismutase (+21.18 %, P < 0.05), catalase (+25.44 %, P < 0.001), glutathione peroxidase (+17.88 %, P < 0.05) and thiobarbituric reactive substances (+28.17 %, P < 0.01) but significantly decreased glutathione reductase (−22.35 %, P < 0.001) level comparative to control, pointing out that administration of cisplatin induced oxidative stress in rats. In groups that received A. melanocarpa extract as drinking water, we noted that the levels of the oxidative stress biomarkers tended to be restored almost to normal levels, which could be a possible good antioxidant used in condition to cisplatin use. Also, we noted a significant (P < 0.001) decrease of total antioxidant capacity in liver and kidney of rats exposed to cisplatin, recovered in those that received chokeberry. Studied trace elements important for the stress oxidative enzymes (Cu, Zn, Fe and Mn) were decreased in cisplatin exposed groups compared to control and mainly all were almost to normal level in groups receiving A. melanocarpa. Conclusion. A. melanocarpa extract due to its antioxidants content could offer protection against free radicals produced as a consequence of cisplatin use.     

Na,K-ATPase in kidneys of rats with hereditary hypertension induced by stress]

It has been found that Na, K-ATP-ase activity in microsomal fraction obtained from the medullar layer of kidneys of stress-sensitive hypertensive rats (SSHR) which were subjected to stress effects is lower by 20-40% than that in the Wistar rats. In hypertensive animals the stress (30-min immobilization) has led to a considerable increase in blood tension. Values I50 for ouabain and dependence of activity on the ratio of Na and K ions in the medium are similar in animals of both lines subjected to the stress. There are also no considerable differences in the protein composition of microsomal fraction from kidneys of rats of both lines. The effects which increase permeability of vesicules (channel-forming agent alamecytin, lubrol WX, freezing-thawing) activate Na,K-ATP-ase in the preparation from the kidneys of rats of the both lines. Under maximum activation there is a removal of differences in activity of the enzyme obtained from the tissues of the SSHR and Wistar animals after the stress action. Blood serum of SSHR rats after the stress inhibits purified Na,K-ATP-ase to the greater extent than the Wistar rat blood serum after the same effect. It is supposed that differences in Na,K-ATP-ase activity in microsomal fraction from the kidneys of rats of the above lines are stipulated by the differences in the "latent" ATP-ase activity.     

L-malate reverses oxidative stress and antioxidative defenses in liver and heart of aged rats

The intracellular levels of antioxidant and free radical scavenging enzymes are gradually altered during the aging process. An age-dependent increase of oxidative stress occurring throughout the lifetime is hypothesized to be the major cause of aging. The current study examined the effects of L-malate on oxidative stress and antioxidative defenses in the liver and heart of aged rats. Sprague-Dawley male rats were randomly divided into four groups, each group consisting of 6 animals. Group Ia and Group IIa were young and aged control rats. Group Ib and Group IIb were young and aged rats treated with L-malate (210 mg/kg body weight per day). L-malate was orally administrated via intragastric canula for 30 days, then the rats were sacrificed and the liver and heart were removed to determine the oxidant production, lipid peroxidation and antioxidative defenses of young and aged rats. Dietary L-malate reduced the accumulation of reactive oxygen species (ROS) and significantly decreased the level of lipid peroxidation in the liver and heart of the aged rats. Accordingly, L-malate was found to enhance the antioxidative defense system with an increased activity of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increased glutathione (GSH) levels in the liver of aged rats, a phenomenon not observed in the heart of aged rats. Our data indicate that oxidative stress was reversed and the antioxidative defense system was strengthened by dietary supplementation with L-malate.     

Sex differences in oxidative stress induced by benzene in rats

Role of sex differences on oxidative stress induced by benzene has been studied in liver, kidney and lungs of rat. It was observed that benzene administration enhanced lipid peroxidation in liver, kidney and lungs of rat, nevertheless, significant variations were recorded in male and female rats. Decrease of GSH and CYTP(450)2E1 was higher in female rats than male rats except lungs. The results suggest that oxidative stress induced by benzene is higher in female rats.     

Involvement of oxidative stress in the impairment in biliary secretory function induced by intraperitoneal administration of aluminum to rats

We have shown that aluminum (Al) induces cholestasis associated with multiple alterations in hepatocellular transporters involved in bile secretory function, like Mrp2. This work aims to investigate whether these harmful effects are mediated by the oxidative stress caused by the metal. For this purpose, the capability of the antioxidant agent, vitamin E, to counteract these alterations was studied in male Wistar rats. Aluminum hydroxide (or saline in controls) was administered ip (27 mg/kg body weight, three times a week, for 90 d). Vitamin E (600 mg/kg body weight) was coadministered, sc. Al increased lipid peroxidation (+50%) and decreased hepatic glutation levels (-43%) and the activity of glutation peroxidase (-50%) and catalase (-88%). Vitamin E counteracted these effects total or partially. Both plasma and hepatic Al levels reached at the end of the treatment were significantly reduced by vitamin E (-40% and -44%, respectively;p< 0.05). Al increased 4 times the hepatic apoptotic index, and this effect was fully counteracted by vitamin E. Bile flow was decreased in Al-treated rats (-37%) and restored to normality by vitamin E. The antioxidant normalized the hepatic handling of the Mrp2 substrates, rose bengal, and dinitrophenyl-S-glutathione, which was causally associated with restoration of Mrp2 expression. Our data indicate that oxidative stress has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage, and the impairment in liver transport function induced by Al and that vitamin E counteracts these harmful effects not only by preventing free-radical formation but also by favoring Al disposal.     

Melatonin and vitamin C administration ameliorate diazepam-induced oxidative stress and cell proliferation in the liver of rats

Abstract.  Objective : Oxidative stress is a likely molecular mechanism in long-term diazepam administration. The benefits of antioxidants (melatonin and vitamin C) against diazepam-induced cell proliferation, DNA synthesis and oxidative damage were investigated in this study. Materials & methods : Four equal-sized groups of male rats [control, diazepam (3 mg/kg), diazepam plus melatonin (5 mg/kg) and diazepam plus vitamin C (50 mg/kg)] were used. Levels of lipid peroxides (LPO), superoxide dismutase (SOD) activity and glutathione (GSH) concentration were measured in tissue homogenates. Cell proliferation and rate of DNA synthesis were detected by autoradiography. Results : Results documented increased labelling index, ³H-thymidine incorporation (DNA synthesis), LPO plus decrease in GSH levels and SOD activity in livers of diazepam-administered rats versus those of controls. When melatonin and vitamin C were given to diazepam-administered rats, they almost attenuated the increase of labelling index, DNA synthesis and LPO, and restored the levels of GSH and SOD activity. Conclusion : These results suggest long-term hazard in use of drugs such as diazepam; they may be toxic and damage terminates in complex liver damage. Furthermore, melatonin and vitamin C may be useful in combating free radical-induced liver injury resulting from hazard and/or repeated diazepam administration.     

Chinese medicinal formula Guan-Xin-Er-Hao protects the heart against oxidative stress induced by acute ischemic myocardial injury in rats

Guan-Xin-Er-Hao (GXEH) is a Chinese medicine formula for treating ischemic heart diseases (IHD) and has a favorable effect. Our aim was to examine whether or not acute oral GXEH could protect the heart against myocardial infarction and apoptosis in acute myocardial ischemic rats. If so, we would explain the antioxidative mechanism involved. The left anterior descending coronary artery was occluded to induce myocardial ischemia in hearts of Sprague-Dawley rats. At the end of the 3 h ischemic period (or 24 h for infarct size), we measured the myocardial infarct size, myocardial apoptosis and the activities of antioxidative enzymes. GXEH reduced infarct size, myocardial apoptosis and the serum level of malondialdehyde (MDA), increased the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and GSH-peroxidase (GPX) activities and the serum level of glutathione (GSH). GXEH exerts significant cardioprotective effects against acute ischemic myocardial injury in rats, likely through its antioxidation and antilipid peroxidative properties, and thus may be used as a promising agent for both prophylaxis and treatment of IHD.     

17beta-estradiol prevents oxidative stress and decreases blood pressure in ovariectomized rats

In this study, we tested whether estrogen deficiency is associated with oxidative stress and decreased nitric oxide (NO) production, which could be responsible for an increased blood pressure in ovariectomized rats. Hemodynamic studies were performed on conscious, chronically instrumented rats. Chronic estrogen replacement on ovariectomized rats lowered blood pressure approximately 13 mmHg, from 119 +/- 3 mmHg in ovariectomized rats to 106 +/- 3 mmHg in ovariectomized-treated rats; it was also accompanied by an increase in cardiac index and vascular conductance, achieving hemodynamic values similar to those shown by sham-operated rats. N(G)-nitro-L-arginine methyl ester administration lowered significantly less the vascular conductance (0.14 +/- 0.01 vs. 0.22 +/- 0.03 and 0.26 +/- 0.01 ml. min(-1). mmHg(-1)/100 g; P < 0.05) in ovariectomized rats than in the sham-operated and estrogen-treated ovariectomized rats, respectively. Estrogen replacement prevented the lower plasma levels of nitrites/nitrates observed in ovariectomized rats. The lower plasma total antioxidant status and reduced thiol groups and the increase in plasma lipoperoxides presented in ovariectomized animals were reestablished with the estrogen treatment. These results show that estrogen administration decreases blood pressure and increases vascular conductance in ovariectomized rats. This effect may be related to an increase in NO synthesis and/or preventing oxidative stress, then improving endothelial function.     

Apomorphine prevents myocardial ischemia/reperfusion-induced oxidative stress in the rat heart

This study examined the hypothesis that low-concentration apomorphine improves postischemic hemodynamic and mitochondrial function in the isolated rat heart model by attenuating oxidation of myocardial proteins. Control and apomorphine-treated hearts were subjected to 35 min of perfusion, 25 min of normothermic global ischemia, and 60 min of reperfusion. Apomorphine (2 microM) was introduced into the perfusate for 20 min starting from the onset of reperfusion. Apomorphine significantly (p <.05) improved postischemic hemodynamic function: work index of the heart (product of LVDP and heart rate) was twice as high in apomorphine-treated hearts compared to controls at the end of reperfusion (p <.01). After isolation of cardiac mitochondria, the respiratory control ratio (RCR) was calculated from the oxygen consumption rate of State 3 and State 4 respiration. Apomorphine significantly improved postischemic RCR (87% of preischemic value vs. 39% in control, p <.05). Using an immunoblot technique, carbonyl content of multiple unidentified myocardial proteins (mitochondrial and nonmitochondrial) was observed to be elevated after global ischemia and reperfusion. Apomorphine significantly attenuated the increased protein oxidation at the end of reperfusion. These results support the conclusion that apomorphine is capable of preventing ischemia/reperfusion-induced oxidative stress and thereby attenuating myocardial protein oxidation and preserving mitochondrial respiration function.     

Modulation of restraint stress induced oxidative changes in rats by antioxidant vitamins

In the present study we examined immobilization stress-induced antioxidant defense changes in rat plasma and also observed the antioxidant effects of pre and post vitamins A, E and C administration (15 mg/Kg of body weight) individually and in combination (vit E + C) on these alterations.Following immobilization stress the circulating activities of superoxide dismutase, catalase and glutathione-S-transferase were decreased, while the level of thiobarbituric acid reactive substances (TBARS) was increased as compared to non-stressed control rats.Post treatment with individual vitamins A, E and C (after exposure to stress) resulted in a less marked alteration of plasma TBARS levels and activities of SOD, GST and catalase as compared to pre vitamin stress or stress alone treatments. Both pre and post vitamin treatments were effective in preventing stress induced derangement of free radical metabolism with a relative dominance by latter. The combined treatment with vitamin E and C did not show any additive antioxidant effect on restraint stress induced altered free radical metabolism, rather a predominant effect similar to vitamin E alone was observed. The prevention of oxidative stress generated in response to restraint stress by the vitamins can be summarized as: vitamin (E + C) i.e. vit E > vit C > vit A, thus combined vitamin (E + C) treatment though showed maximum preventive effect, but was similar to vitamin E treatment alone, in terms of the circulating activities of SOD, GST, catalase and TBARS levels.     

Effect of NAD and ADP on glycolysis in the kidneys and liver of rats during ischemia

Experiments on albino rats have shown that kidney ischemia and its simulation by the anaerobic incubation of postmitochondrial kidney homogenate fraction without a substrate induce a considerable damage of the glycolytic system at the stage of the glucoso-6-phosphate transformation into fructoso-1.6-diphosphate and a less pronounced damage in the fructoso-1.6-diphosphate transformation into lactate. Administration of adenosine diphosphate (ADP) and nicotinamide adenine dinucleotide (NAD) to rats before kidney vessel occlusion or their addition to the postmitochondrial fraction before the anaerobic incubation without a substrate decreased a degree of the glycolytic system damage. The damage of the glycolytic system and protective action of NAD are also detected under simulation of liver ischemia. Possible mechanisms of the ischemic damage in the glycolytic liver and kidney tissue system are discussed.     

Resveratrol prevents oxidative stress and inhibition of Na(+)K(+)-ATPase activity induced by transient global cerebral ischemia in rats

Increased oxidative stress and energy metabolism deficit have been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In this study, we investigated the oxidative mechanisms underlying the neuroprotective effects of resveratrol, a potent polyphenol antioxidant found in grapes, on structural and biochemical abnormalities in rats subjected to global cerebral ischemia. Experimental model of transient global cerebral ischemia was induced in Wistar rats by the four vessel occlusion method for 10 min and followed by different periods of reperfusion. Nissl and fluoro jade C stained indicated extensive neuronal death at 7 days after I/R. These findings were preceded by a rapid increase in the generation of reactive oxygen species (ROS), nitric oxide (NO), lipid peroxidation, as well as by a decrease in Na⁺K⁺-ATPase activity and disrupted antioxidant defenses (enzymatic and non-enzymatic) in hippocampus and cortex. Administrating resveratrol 7 days prior to ischemia by intraperitoneal injections (30 mg/kg) significantly attenuated neuronal death in both studied structures, as well as decreased the generation of ROS, lipid peroxidation and NO content. Furthermore, resveratrol brought antioxidant and Na⁺K⁺-ATPase activity in cortex and hippocampus back to normal levels. These results support that resveratrol could be used as a preventive, or therapeutic, agent in global cerebral ischemia and suggest that scavenging of ROS contributes, at least in part, to resveratrol-induced neuroprotection.     

Melatonin reduces oxidative stress induced by ochratoxin A in rat liver and kidney

Melatonin (MEL) displays antioxidant and free radical scavenger properties. In the present study, the effect of MEL on the oxidative stress induced by ochratoxin A (OTA) administration in rats was investigated. Four groups of 15 rats each were used: controls, MEL-treated rats (5 mg/kg body mass), OTA-treated rats (250 μg/kg) and MEL+OTA-treated rats. After 4 weeks of treatment, the levels of malondialdehyde (MDA), a lipid peroxidation product (LPO) were measured in serum and homogenates of liver and kidney. Also, the levels of glutathione (GSH), and activities of glutathione reductase (GR), glutathione peroxidase (GSPx), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in liver and kidney were determined. In OTA-treated rats, the levels of LPO in serum and in both liver and kidney were significantly increased compared to levels in controls. Concomitantly, the levels of GSH and enzyme activities of SOD, CAT, GSPx and GR in both liver and kidney were significantly decreased in comparison with controls. In rats received MEL+OTA, the changes in the levels of LPO in serum and in liver and kidney were not statistically significant compared to controls. Concomitantly, the levels of GSPx, GR and GST activities in both liver and kidney tissues were significantly increased in comparison with controls. Similar increases in GSPx, GR and GST activities were also observed in MEL-treated rats when compared with controls. In conclusion, the oxidative stress may be a major mechanism for the toxicity of OTA. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and stimulation of GST activities. Thus, clinical application of melatonin as therapy should be considered in cases of ochratoxicosis.