Cardioprotective properties of Artemisia herba alba nanoparticles against heart attack in rats: A study of the antioxidant and hypolipidemic activities

Recently, pharmaceutical scientists' interest has increased to find novel pharmaceutical natural substances with potent antioxidant capacity and very low side effects to be used safely in preventive medicine. One of the most common types of diseases with a large spread globally is cardiovascular diseases, which cause a high rate of deaths annually. The present study evaluated the use of Artemisia herba alba leaves’ extract (AHALE) and AHALE zinc oxide nanoparticles (AHALE–ZnONPs) against isoproterenol (ISO) inducing myocardial infarction (MI) in male rats. Several groups of Wistar male rats fed a high-fat diet (HFD) were pretreated with several doses of AHALE or AHALE–ZnONPs for one month followed by exposure to ISO for two days. After treatment, samples of the rats’ heart tissues and blood were collected for several molecular biological and biochemical analyses. Heart enzymes, antioxidant enzymes, lipid peroxidation compounds, lipid markers, activities, ROS generation, apoptosis, DNA damage and expression of lipid metabolism genes were analyzed in rats pretreated with AHALE or AHALE–ZnONPs followed by exposure to ISO. The results showed an increase in the levels of AST, ALT, LDH, CK, CK-MB, and cTnT (heart markers), elevation in TG, TC, and LDL levels (lipid profile markers), levels of TBARS and LOOH (lipid peroxidation products), ROS generation, DNA damage, apoptosis, and upregulation of PPAR-α, ADD1, FASN, and ACC genes in animals exposed to ISO in comparison with the control animals. Moreover, a decrease in antioxidant enzyme activities, including GPx, GRx, and GST, was observed in animals exposed to ISO in comparison with control rats. In male rats pretreated with AHALE or AHALE–ZnONPs followed by exposure to ISO, the oxidative stress induced by ISO was prevented. The results suggest that Artemisia extract could be considered for use as one of the natural compounds for prevention of atherosclerosis and heart diseases due to its high antioxidant and hypolipidemic activities. The reduced oxidative stress of Artemisia extract may be a result of the existence of flavonoids and phenolic substances.     

Response of hepatic antioxidant system to exercise training in aging female rat

This study was undertaken to investigate the effect of exercise training on aging in the hepatic oxidative status and antioxidant defense of female albino rat. Two age groups of 3 months and 12 months old Wistar strain female albino rats were given chronic exercise training for a period of 12 weeks. The antioxidant enzyme assays were carried out by the standard methods. Lower (P<0.01) activities of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) by 21%, 44% and 63% respectively was observed in the older rats when compared to younger rats. Also, glutathione (GSH) levels were 42% lower (P<0.01) in older than younger animals. Exercise training to the 12 months aged rats significantly (P<0.01) elevated these antioxidant enzyme activities and GSH content, when compared to older control rats. These levels are almost equal to the values observed in the younger control rats. The levels of lipid peroxidation end product, malondialdehyde (MDA) the major indicator of oxidative stress, was found to increase with age (11%) and exercise training caused further elevation (28% of control). The present findings imply that the reactive oxygen species that are generated due to aging process were detoxified by the exercise induced antioxidant system in the liver tissue. These findings are also in agreement with similar changes in male animals, which clearly envisage no gender difference in the amelioration of the antioxidant enzyme system in older age due to exercise. In conclusion, it can be stated that twelve weeks treadmill exercise training has beneficial effect in improving antioxidant defense capacity by augmenting SOD, CAT and GR activities and GSH levels of older rats, thereby preventing oxidative damage to the liver tissue.     

Exercise training combined with antioxidant supplementation prevents the antiproliferative activity of their single treatment in prostate cancer through inhibition of redox adaptation

In preclinical models, exercise training (ET) or pomegranate juice (PJ) prevents prostate cancer progression. Here, we hypothesized that physical exercise combined with antioxidants could induce synergistic effects through oxidative stress modulation. Forty male Copenhagen rats with prostate tumors were divided into four groups: control, PJ, ET, and PJ+ET. Rats from the PJ group consumed 750 µl of PJ daily, rats from the ET group ran on a treadmill 5 days per week, and PJ+ET rats received the combined treatment. Each week, tumor growth was evaluated. After 4 weeks of treatment, the rats were euthanized and blood, muscles, and tumors were collected. Tumor Ki67, extracellular signal-regulated kinase (ERK) activation, Bcl-2 expression, and enzymatic and nonenzymatic antioxidant defenses, as well as oxidative stress markers (oxidized base, lipid peroxidation, protein carbonylation), were measured. PJ or ET significantly decreased prostate tumor proliferation (Ki67 staining, p<0.05) through the modulation of ERK phosphorylation, whereas the combination of treatments did not limit cancer progression. PJ significantly reduced Bcl-2 expression in tumors (p<0.05) and the combination of PJ and ET prevented this effect. PJ or ET increased enzymatic antioxidant defenses in muscle, PJ increased nonenzymatic antioxidant defenses in plasma and whole blood. In addition, PJ reduced TBARS and 8-oxodGuo levels in tumors as well as ET (p<0.05), whereas protein carbonyl levels were not affected by these two strategies. Paradoxically, association of PJ+ET did not increase antioxidant defenses and no reduction in oxidative stress markers was induced. Loading cancer cells with antioxidants blunts the positive effects of ET and interferes with important reactive oxygen species-mediated physiological processes such as antioxidant adaptations.     

Basic Fibroblast Growth Factor Attenuates Bisphosphonate-Induced Oxidative Injury but Decreases Zinc and Copper Levels in Oral Epithelium of Rat

Recent studies have reported oxidative damage due to bisphosphonate (BP) in various cancer tissues and neurons, although basic fibroblast growth factor (bFGF) induced antioxidant effects in the cells. The bFGF may modulate the BP-induced oxidative stress in oral epithelium of rats. This study was undertaken to explore possible beneficial antioxidant effects of bFGF on oxidative stress induced by BP in oral epithelium of rats. Twenty-eight rats were equally divided into four groups. The first group was used as control. The second, third and fourth groups intraperitoneally received BP (zoledronic acid), bFGF and BP + bFGF. At the end of 10 weeks, the rats were sacrificed, and oral epithelium samples were taken for analyses. In BP group, the lipid peroxidation levels were increased in the oral epithelium, while the activities of glutathione peroxidase (GSH-Px) and the concentrations of total antioxidant status (TAS) were decreased. In rats treated with bFGF, lipid peroxidation levels decreased, and the activities of GSH-Px and concentrations of TAS improved in the oral epithelium. However, zinc and copper levels were decreased in the oral epithelium by BP and bFGF treatments. Concentrations of vitamin E and reduced glutathione in the samples did not change in the groups. In conclusion, treatment with bFGF modulated the antioxidant redox system and reduced the oral epithelium oxidative stress induced by BP. However, zinc and copper levels were decreased by BP and bFGF treatments.     

Garlic and vitamin E provides antioxidant defence in tissues of female rats treated with nicotine

Nicotine is known to induce oxidative stress in rat tissues and the antioxidant properties of garlic have been reported. This study was designed to determine if the peroxidative damage caused by nicotine administration can be effectively prevented with garlic juice, and vitamin E, a known antioxidant.Four groups of six rats each were divided into: Group I: (control) received 0.2ml of 0.9% normal saline, group II (received nicotine 0.6mg/kg b.w subcutaneously), group III (received nicotine 0.6mg/kg b.w + garlic juice 100mg/kg b.w orally), and group IV (received nicotine 0.6mg/kg b.w + Vitamin E 100mg/kg b.w orally). All animals were treated for 21 days. The pituitary gland, ovary, uterus, heart, liver and kidney of the animals were harvested, weighed and homogenized. Malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were then measured.Concentration of MDA was significantly increased in tissues of nicotine treated rats when compared with the control. In group III and IV, MDA levels were significantly reduced when compared with nicotine group. The activities of SOD and GSH significantly decreased in group II (nicotine only) rat tissues, while it was significantly increased in group III and IV rat tissues. The study showed that garlic juice extract (100mg/kg b.w) and vitamin E (100mg/kg b.w) administration prevented oxidative damage in rat tissues treated with nicotine. The study also showed that vitamin E has a more potent antioxidant activity than garlic juice in preventing nicotine induced oxidative damage in rat. Keywords: Nicotine, Vitamin E, Garlic, antioxidant.     

Age-related effect of aerobic exercise training on antioxidant and oxidative markers in the liver challenged by doxorubicin in rats

The aims of the current study were to investigate the oxidant and antioxidant status of liver tissue challenged by doxorubicin and to examine the possible protective effects of aerobic exercise on doxorubicin-induced oxidative stress. Seventy-two rats were divided into three age groups (Young, Adult, and Elderly) with three treatment subgroups consisting of eight rats per age group: doxorubicin, aerobic exercise?+?doxorubicin, and aerobic exercise?+?saline. The experimental groups performed regular treadmill running for 3 weeks. Doxorubicin was administered by i.p. injection at a dosage of 20?mg kg^?1 while the aerobic exercise?+?saline group received saline of a comparable volume. Heat shock protein 70, malondialdehyde, glutathione peroxidase, and protein carbonyl were determined from the liver homogenates following the intervention period. Treatment with doxorubicin induced hepatotoxicity in all groups with lower values of oxidative stress in young compared with the older groups. The inclusion of aerobic exercise training significantly increased heat shock protein 70 and antioxidant enzyme levels (glutathione peroxidase) whereas it decreased oxidative stress biomarkers (malondialdehyde and protein carbonyl) for all age groups. These results suggest that aerobic exercise training may be a potential, non-drug strategy to modulate doxorubicin-induced hepatotoxicity through its positive impact on antioxidant levels and oxidative stress biomarkers.     

低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响

Nrf2可调节多种抗氧化酶的表达,Nrf2的缺失可能影响机体的运动能力,而低氧可提高机体的抗氧化能力并改善运动能力。为了考察低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响,本研究分别在常氧和低氧环境(12%氧浓度)中对野生型大鼠和Nrf2敲除大鼠进行4周的跑台运动。研究显示,低氧运动可提高野生型大鼠的跑台运动力竭时间,Nrf2敲除可缩短大鼠的力竭时间;低氧运动可上调大鼠的Nrf2 m RNA表达量;Nrf2敲除明显抑制HIF-1α蛋白表达,而低氧运动可上调野生型和Nrf2敲除大鼠的HIF-1α蛋白表达;Nrf2敲除大鼠的骨骼肌ROS水平明显升高,并且低氧均可降低野生型和Nrf2敲除大鼠骨骼肌ROS水平。低氧运动可上调Nrf2敲除大鼠的CAT和GSH-PX蛋白表达。苏木精和伊红(HE)染色显示,Nrf2敲除大鼠在力竭跑台运动完成后出现更严重的骨骼肌病理改变,而低氧运动可减轻骨骼肌损伤。本研究认为,Nrf2敲除导致了大鼠骨骼肌中抗氧化酶的抑制及ROS的过量累积,从而造成了骨骼肌损伤并降低了运动能力。此外,低氧可通过上调Nrf2的表达,进而激活HIF-1α及抗氧化酶活性,从而提高运动能力,并防止骨骼肌损伤。     

A combination of soy isoflavone supplementation and exercise improves lipid profiles and protects antioxidant defense-systems against exercise-induced oxidative stress in ovariectomized rats

Menopause is often accompanied with weight gain, metabolic lipid abnormalities, and oxidative stress. In this study, we investigated the combined effects of exercise and soy isoflavone supplementation on the lipid profiles and antioxidant capacities of ovariectomized rats. Twenty-five female Sprague-Dawley rats were divided into 5 groups: sham-operated, ovariectomized (OVX), OVX with exercise (OVX+EX), OVX with soy isoflavone supplementation (OVX+ISO), and OVX with both soy isoflavones and exercise (OVX+ISO+EX). After 12 weeks of intervention, antioxidant status was evaluated in collected blood samples by the ferric reducing ability of plasma (FRAP), glutathione (GSH) content, and sodium oxide dismutase (SOD) activity. DNA damage in the lymphocytes was determined using alkaline single-cell gel electrophoresis (the Comet assay). Although there were no significant differences in weight gain and food intake, weight gain was lower in OVX+EX, OVX+ISO, and OVX+ISO+EX than in OVX. OVX+EX, OVX+ISO, and OVX+ ISO+EX showed a significant decrease in total cholesterol, triglycerides, and LDL-cholesterol compared to OVX. The soy isoflavone supplemented group had significantly increased FRAP values and GSH contents in contrast to no changes in the exercised group, whereas exercise markedly increased SOD activity and H2O2-induced DNA tail length and tail moment. Exercise with soy isoflavone supplementation significantly increased FRAP values and had no difference on SOD activity, including DNA damage. These results demonstrate that a combined treatment of moderate exercise and soy isoflavone supplementation could exert a beneficial effect on weight control and lipid profiles, and offer protection from exercise-induced oxidative stress in postmenopausal women.     

Physiological basis for effect of physical conditioning on chronic ethanol-induced hypertension in a rat model

The study aim was to investigate the interaction of physical conditioning and chronic ethanol ingestion on blood pressure (BP), heart rate (HR), nitric oxide (NO) and oxidants/antioxidants balance in the plasma of rats. Male Fisher rats were divided into four groups of seven animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks; (2) ethanol (4 g kg⁻¹, orally) daily for 12 weeks; (3) exercise training on treadmill plus sucrose daily for 12 weeks and (4) exercise training on treadmill followed by ethanol (4 g kg⁻¹, orally) daily for 12 weeks. The body weight, BP and HR were recorded every week. The animals were sacrificed under ether anesthesia after 12 weeks, blood collected in heparinzed vials, plasma isolated and analyzed. The results show that exercise training significantly lowered the weight gain 6–12 weeks in ethanol treated rats compared to ethanol alone or control rats. The mean arterial BP was significantly elevated 6–12 weeks after ethanol ingestion without significant alterations in HR. Exercise training lowered the BP close to the normal control values in ethanol fed rats. Ethanol significantly decreased the plasma NO levels, reduced to oxidized glutathione ratio (GSH/GSSG) and antioxidant enzymes-superoxide dismutase (CuZn-SOD, and Mn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities while plasma NADPH oxidase activity and malondialdehyde (MDA) levels were significantly elevated compared to control. Exercise training significantly restored the depletion of plasma NO levels, GSH/GSSG ratio, and antioxidant enzyme activities and normalized the MDA levels and NADPH oxidase activity in the plasma of ethanol treated rats. The study concluded that physical conditioning attenuates the chronic ethanol-induced hypertension by augmenting the NO bioavailability and reducing the oxidative stress response in the plasma of rats.     

Effect of T3 on metabolic response and oxidative stress in skeletal muscle from sedentary and trained rats

We investigated whether swim training modifies the effect of T₃-induced hyperthyroidism on metabolism and oxidative damage in rat muscle. Respiratory capacities, oxidative damage, levels of antioxidants, and susceptibility to oxidative challenge of homogenates were determined. Mitochondrial respiratory capacities, H₂O₂ release rates, and oxidative damage were also evaluated. T₃-treated rats exhibited increases in muscle respiratory capacity, which were associated with enhancements in mitochondrial respiratory capacity and tissue mitochondrial protein content in sedentary and trained animals, respectively. Hormonal treatment induced muscle oxidative damage and GSH depletion. Both effects were reduced by training, which also attenuated tissue susceptibility to oxidative challenge. The changes in single antioxidant levels were slightly related to oxidative damage extent, but the examination of parameters affecting the susceptibility to oxidants indicated that training was associated with greater effectiveness of the muscle antioxidant system. Training also attenuated T₃-induced increases in H₂O₂ production and, therefore, oxidative damage of mitochondria by lowering their content of autoxidizable electron carriers. The above results suggest that moderate training is able to reduce hyperthyroid state-linked tissue oxidative damage, increasing antioxidant protection and decreasing the ROS flow from the mitochondria to the cytoplasmic compartment.     

The effect of thyroxine administration on lipid peroxidation in different tissues of rats with hypothyroidism

Thyroid dysfunctions bring about pathological changes in different organs of the body. Findings obtained from in vivo and in vitro studies point out that thyroid hormones have a strong impact on oxidative stress. The present study was conducted to demonstrate how high-dose thyroxin administration for one week affected oxidative damage formed in experimental hypothyroidism. The study was carried out with 30 Spraque-Dawley species male rats. The experimental animals were divided into 3 groups (Group 1, control; Group 2, hypothyroidism; Group 3, hypothyroidism + thyroxine administration). Malondialdehyde (MDA) and glutathione (GSH) levels were determined in cerebral, hepatic and cardiac tissues after the experimental period. MDA and GSH levels in cerebral, hepatic and cardiac tissues of hypothyroidism + thyroxine supplemented group were higher than those in the control and hypothyroidism groups (p<0.001). The same parameters were higher in the control group than those in the hypothyroidism group (p<0.001). The results of the present study show that hypothyroidism reduced the oxidative damage in cerebral, hepatic and cardiac tissues of rats. However, high-dose thyroxine administration in addition to induced hypothyroidism increased oxidative damage in the same tissues and that this damage could not be prevented despite the increase in the antioxidant system activity.     

Cardioprotective effect of the alcoholic extract of Terminalia arjuna bark in an in vivo model of myocardial ischemic reperfusion injury

The present study was designed to investigate the effects of chronic administration of the alcoholic extract of Terminalia arjuna (TAAE) bark on isoproterenol induced myocardial injury. The TAAE was administered orally to Wistar albino rats (150-200 g) in three different doses, by gastric gavage [3.4 mg/kg: (T1), 6.75 mg/kg: (T2) and 9.75 mg/kg: (T3)] 6 days/week for 4 weeks. At the end of this period, all the animals, except the normal untreated rats that served as the control group, were administered isoproterenol (ISO) 85 mg/kg, S.C., for two consecutive days to induce in vivo myocardial injury. After 48 hours rats were anaesthetized with anaesthetic ether, then sacrificed and the hearts were harvested for biochemical and histological studies. A significant rise in myocardial thiobarbituric acid reactive substances (TBARS) and loss of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (suggestive of increased oxidative stress) occurred in the hearts subjected to in vivo myocardial ischemic reperfusion injury. The 6.75 mg/kg TAAE treatment group (baseline) shows a significant increase in myocardial TBARS as well as endogenous antioxidants (GSH, SOD, and catalase), but not in the other treatment groups. In in vivo ischemic reperfusion injury of the TAAE treated rats there was a significant decrease in TBARS in all the groups. In 6.75 mg/kg treatment group, a significant rise in the levels of GSH, SOD and catalase were observed, and it shows better recovery profile than the other groups subjected to in vivo ischemic reperfusion injury. In histological studies, all the groups, except the isoproterenol treated group, showed preserved myocardium. The present study demonstrates that the 6.75 mg/kg TAAE augments endogenous antioxidant compounds of the rat heart and also prevents the myocardium from isoproterenol induced myocardial ischemic reperfusion injury.     

The effects of vitamin C supplementation on oxidative stress and antioxidant content in the brains of chronically exercised rats

The purpose of this study was to ascertain whether vitamin C supplementation during chronic exercise training alters rat brain antioxidant content. Female Wistar albino rats were exercised on a treadmill for 30 min/day for 6.5 weeks and were administered daily intraperitoneal injections of vitamin C (20 mg/kg). After the training period, chronically exercised rats showed no significant changes in total brain thiobarbituric acid reactive substances (TBARS) levels. In contrast, rats supplemented with vitamin C during the training period showed significantly elevated brain TBARS levels. If such results were extrapolated to man, where vitamin supplementation is a common practice, this would indicate that vitamin C supplementation may not protect brain tissue against exercise-induced oxidative damage, in such circumstances, this water-soluble antioxidant behaves as a pro-oxidant. (Mol Cell Biochem xxx: 135–138, 2005)     

Co-enzyme Q10 and acetyl salicylic acid enhance Hsp70 expression in primary chicken myocardial cells to protect the cells during heat stress

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and proliferative obstruction of pulmonary vessels, which promotes a progressive increase in pulmonary vascular resistance (PVR). The effect of exercise training on oxidative stress, metabolism, and markers of nitric oxide (NO) and endothelin-1 (ET-1) was analyzed in the lung tissue of rats with PAH induced by monocrotaline (MCT).Twenty-four Wistar rats were divided into four groups (5–7 animals): sedentary control (SC), sedentary MCT (SM), trained control (TC), and trained MCT (TM). The TC and TM groups participated in a treadmill training protocol (60% VO₂ max) for 5 weeks, 3 weeks of which were performed after the injection of MCT (60 mg/kg i.p.) or saline. MCT administration promoted an increase in PVR and right ventricle hypertrophy, and reduction of right ventricle systolic function assessed by echocardiography. These changes were not improved by exercise training. The activity of NO synthase was reduced in the animals of the TC, TM, and SM groups. No significant differences were found in total nitrite concentration and expression of endothelial NO synthase. Moreover, the TM group showed strong staining for iNOS and nitrotyrosine, suggesting an increase in oxidative stress in these animals. In parallel, reduced expression of type B ET-1 receptors was noticed in the SM and TM groups in comparison to controls. In conclusion, the aerobic training protocol was unable to mitigate changes in the metabolism of NO and ET-1, probably because of the disease severity in these animals, especially in the TM group.     

N-Acetylcysteine Attenuates Copper Overload-Induced Oxidative Injury in Brain of Rat

Copper is an integral part of many important enzymes involved in a number of vital biological processes. Even though it is essential to life, at elevated tissue concentrations, copper can become toxic to cells. Recent studies have reported oxidative damage due to copper in various tissues. Considering the vulnerability of the brain to oxidative stress, this study was undertaken to explore possible beneficial antioxidant effects of N-acetylcysteine on oxidative stress induced by copper overload in brain tissue of rats. Thirty-two Wistar rats were equally divided into four groups. The first group was used as control. The second, third, and fourth groups were given 1 g/L copper in their drinking water for 1 month. At the end of this period, the group 2 rats were sacrificed. During the next 2 weeks, the rats in group 3 were injected intraperitoneally with physiological saline and those in group 4 with 20 mg/kg intraperitoneal injections of N-acetylcysteine. In group 2 the lipid peroxidation and nitric oxide levels were increased in the brain cortex while the activities of superoxide dismutase and catalase and the concentration of glutathione were decreased. In rats treated with N-acetylcysteine, lipid peroxidation decreased and the activities of antioxidant enzyme improved in the brain cortex. In conclusion, treatment with N-acetylcysteine modulated the antioxidant redox system and reduced brain oxidative stress induced by copper.     

Correlation between oxidative Stress and Alteration of Intracellular Calcium Handling in Isoproterenol-Induced Myocardial Infarction

Myocardial Ca²⁺ overload and oxidative stress are well documented effects associated to isoproterenol (ISO)-induced myocardial necrosis, but information correlating these two issues is scarce. Using an ISO-induced myocardial infarction model, 3 stages of myocardial damage were defined: pre-infarction (0–12 h), infarction (12–24 h) and post-infarction (24–96 h). Alterations in Ca²⁺ homeostasis and oxidative stress were studied in mitochondria, sarcoplasmic reticulum and plasmalemma by measuring the Ca²⁺ content, the activity of Ca²⁺ handling proteins, and by quantifying TBARs, nitric oxide (NO) and oxidative protein damage (changes in carbonyl and thiol groups). Free radicals generated system, antioxidant enzymes and oxidative stress (GSH/GSSG ratio) were also monitored at different times of ISO-induced cardiotoxicity. The Ca²⁺ overload induced by ISO was counterbalanced by a diminution in the ryanodine receptor activity and the Na⁺-Ca⁺² exchanger as well as by the increase in both calcium ATPases activities (vanadate- and thapsigargine-sensitive) and mitochondrial Ca²⁺ uptake during pre-infarction and infarction stages. Pro-oxidative reactions and antioxidant defences during the 3 stages of cardiotoxicity were observed, with maximal oxidative stress during the infarction. Significant correlations were found among pro-oxidative reactions with plasmalemma and sarcoplasmic reticulum Ca²⁺ ATPases, and ryanodine receptor activities at the onset and development of ISO-induced infarction. These findings could be helpful in the design of antioxidant therapies in this pathology.     

Oxidative stress induces vascular heme oxygenase-1 expression in ovariectomized rats

Heme oxygenase-1 (HO-1), an inducible stress protein, has been implicated in cytoprotection against oxidative stress in vitro and in vivo. Estrogens also have antioxidant effects. This study investigated the time course of HO-1 and inducible nitric oxide synthase (iNOS) expression in the aortas of ovariectomized rats, and the regulatory relationship between the NO/NOS and the carbon monoxide/HO systems. HO-1 and iNOS protein expression was induced by ovariectomy (Ovx) and was extremely high 2-6 weeks after Ovx compared with the sham-operated group. Expression of the constitutive enzymes HO-2 and endothelial NOS did not differ significantly between sham-operated and Ovx rats. 17beta-Estradiol (E(2)) replacement reversed these changes in rats after Ovx. Long-term treatment with the antioxidant tempol significantly inhibited HO-1 and iNOS expression. The iNOS inhibitor aminoguanidine significantly suppressed the induction of HO-1. Oxidized glutathione in the hearts of Ovx rats increased gradually, with significant elevation at 3-6 weeks after Ovx compared with the sham-operated group, whereas plasma levels of NO metabolites were significantly reduced 4-6 weeks after Ovx. Treatment with the HO inhibitor zinc protoporphyrin IX blocked HO-1 induction, but significantly increased the plasma levels of NO metabolites. In conclusion, HO-1 is induced by oxidative stress resulting from E(2) depletion. The NO/iNOS system contributes to the induction of HO-1, which may subsequently suppress iNOS activity to modulate vasculoprotective effects after menopause.     

Dexpanthenol reduces diabetic nephropathy and renal oxidative stress in rats

Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress contributes to the development of diabetic complications. Dexpanthenol (Dxp) is the biological active form of pantothenic acid. We investigated whether Dxp administration could decrease oxidative stress as a way to treat renal complications of diabetes mellitus (DM). Thirty-two male Wistar albino rats were divided into four groups: control, Dxp, DM and DM + Dxp. Experimental diabetes was induced by a single dose of streptozotocin (STZ). After administration of STZ, the DM + Dxp group was administered 500 mg/kg Dxp intraperitoneally every day for 6 weeks. At the end of the study, blood glucose levels were measured and rats were sacrificed. Kidneys were embedded in paraffin, sectioned and stained with hematoxylin and eosin, and periodic acid-Schiff. The mean malondialdehyde levels, glutathione peroxidase, superoxide dismutase and catalase activities, and total antioxidant and total oxidant status also were measured. The control group was normal in histological appearance. We observed congestion, inflammation, glomerulosclerosis, tubular desquamation, loss of villi and hydropic degeneration in tubule cells in the DM group. Indicators of oxidative stress were elevated and antioxidant activity was reduced in the DM group compared to controls. In the DM + Dxp group, oxidative stress was decreased, antioxidant activity was increased and histopathological changes were reduced compared to the DM group. We found that Dxp exhibited ameliorative effects on STZ induced diabetic nephropathy by increasing antioxidant activity.     

Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide‐induced hemorrhagic cystitis in rat

Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting side effect of CP. Recent studies show that aminogaunidine, an inhibitor of inducible nitric oxide synthase is a potent antioxidant and prevents changes caused by oxidative stress such as depletion of antioxidant activity and tissue injury. The purpose of the study is to investigate the effect of aminoguanidine on parameters of oxidative stress, antioxidant enzymes and bladder injury caused by CP. Adult male rats were randomly divided into four groups. Control rats were administered saline; the AG control group received 200 mg/kg body wt of aminoguanidine; The CP group received a single injection of CP at the dose of 150 mg/kg body wt intraperitoneally. The CP + AG group received aminoguanidine (200 mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats were sacrificed 16 h after CP/saline administration. The bladder was used for light microscopic studies and biochemical studies. The markers of oxidative damage including protein carbonyl content, protein thiol, malondialdehyde and conjugated dienes were assayed in the homogenates along with the activities of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase and glutathione S transferase. In the bladders of CP treated rats edema of lamina propria with epithelial and sub‐epithelial hemorrhage was seen. All the parameters of oxidative stress that were studied were significantly elevated in the bladders of CP treated rats. The activities of the antioxidant enzymes were significantly lowered in the bladders of CP treated rats. Aminoguanidine pretreatment prevented CP‐induced oxidative stress, decrease in the activities of anti‐oxidant enzymes and reduced bladder damage. The results of the present study suggest the antioxidant role for aminoguanidine in CP‐induced bladder damage. Copyright © 2008 John Wiley & Sons, Ltd.     

Effect of aerobic exercise intervention on DDT degradation and oxidative stress in rats

Dichlorodiphenyltrichloroethane (DDT) reportedly causes extensively acute or chronic effects to human health. Exercise can generate positive stress. We evaluated the effect of aerobic exercise on DDT degradation and oxidative stress.Main methods: Male Wistar rats were randomly assigned into control (C), DDT without exercise training (D), and DDT plus exercise training (DE) groups. The rats were treated as follows: DDT exposure to D and DE groups at the first 2 weeks; aerobic exercise treatment only to the DE group from the 1st day until the rats are killed. DDT levels in excrements, muscle, liver, serum, and hearts were analyzed. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels were determined. Aerobic exercise accelerated the degradation of DDT primarily to DDE due to better oxygen availability and aerobic condition and promoted the degradation of DDT. Cumulative oxidative damage of DDT and exercise led to significant decrease of SOD level. Exercise resulted in consistent increase in SOD activity. Aerobic exercise enhanced activities of CAT and GSH-Px and promoted MDA scavenging. Results suggested that exercise can accelerate adaptive responses to oxidative stress and activate antioxidant enzymes activities. Exercise can also facilitate the reduction of DDT-induced oxidative damage and promoted DDT degradation. This study strongly implicated the positive effect of exercise training on DDT-induced liver oxidative stress.