Free Radical Metabolism Research Articles

Effects of exercise on learning and memory, oxidative stress and nNOS expression in marginal division of striatum of ovariectomized rats.

Since previous studies have shown that ovariectomy impairs memory and cognition, we investigated whether 8-week treadmill exercise would affect ovariectomy-induced memory deficits and explore the possible mechanisms of physical exercise influencing spatial learning and memory of the ovariectomized rats by detecting the rat's brain free radical metabolism and counting neural nitric oxide synthase (nNOS) expression in marginal division of the striatum (MrD). Forty female rats were assigned to one of the following groups: SHAM, SHAM+E, OVX and OVX+E group. The rats of SHAM and OVX group kept normal activities and the SHAM+E and OVX+E group rats undertook an 8-week training with progressively increasing load. Then the cognitive function was evaluated using 8-arm radial maze test. Also, oxidative stress markers in the MrD were also evaluated and the nNOS expression in MrD was detected and analyzed. Results show that ovariectomized rats were impaired in learning and memory and brain SOD (superoxide dismutase), CAT (catalase) activities were dropped and MDA (malondialdehyde) level increased via ovariectomy, nNOS expression in MrD was reduced in comparison with the SHAM group rats. While treadmill exercise significantly alleviated learning and memory decline and prevented oxidative brain damage induced by ovariectomy, nNOS expression in MrD significantly enhanced. These findings support ovariectomy can impair spatial learning and memory of the rats, the regular treadmill exercise appears to exert a protective effect against ovariectomy, induced spatial memory impairment through inhibition of oxidative stress and up-regulation MrD nNOS expression.

Assessment of erythrocyte SOD activity in different stages of Essential Hypertension patients

Oxidative stress has been found to be associated with most of the diseases. In the past several years, much interest has arisen over the involvement of free radical metabolism in the disturbance in endothelial or intimal cells of blood vessels, which play an important role in the pathogenesis of essential hypertension (HT). Although limited information is available on the activity of antioxidant enzyme erythrocyte superoxide dismutase (SOD) and its relation with blood pressure in patients with HT, alteration in their activity with severity of disease is still obscure. The objective of present study was to estimate the activity of SOD in hypertensive subjects and to determine the variation in erythrocyte SOD activity with increasing blood pressure. In the present study, erythrocyte SOD activity was measured in 90 hypertensive subjects (30-60 years) which were categorized into three groups as pre-hypertension, stage I HT and stage II HT (depending upon their blood pressure) and statistically compared it with that of 30 healthy individuals, served as control. Erythrocyte SOD activity was found to be significantly low in each patient group as compared to control (P<0.001). These activities were also low among three groups of essential hypertension. These findings suggest that depletion in erythrocyte SOD activity with subsequent rise in blood pressure is due to its superoxide anion scavenging action against hypertension induced production of free radical in the body. Thus, erythrocyte SOD activity may be an effective marker of oxidative stress in different stages of essential hypertension and its related complications.

Antioxidant and antitumor activities of Capparis spinosa L. and the related mechanisms.

The 'ethnodrug' Capparisspinosa L. has several pharmacological activities. First, it was found in previous experiments that an ethyl acetate extract of CapparisspinosaL. (CSE) exhibited antioxidant activity. In order to further research this finding, the present study investigate the blood biochemical indices, injury, energy metabolism, oxidative damage and mitochondrial membrane potential (Δψm) level of cardiac cells to study the effect of CSE on doxorubicin-induced cardiac toxicity. CSE had protective effects on the cardiac toxic effect of doxorubicin, and decreased the activity of lactic dehydrogenase (LDH) and creatine kinase (CK). CSE increased the ability of myocardial tissue to scavenge free radicals, inhibited lipid peroxidation, increased recovery activity of antioxidant enzymes, adjusted the energy metabolism of myocardial tissue, inhibited the generation of a large number of ROS in the cells, raised the level of Δψm, and improved the metabolism of free radicals. CSE demonstrated protective effects on doxorubicin-induced myocardial damage. Second, the quaternary ammonium hydroxide of CapparisspinosaL. (CSQAH) was found to possess antitumor activity, such as antiproliferative and apoptosis-induced effects on HepG2 cells. We investigated the regulatory mechanism of HepG2 apoptosis induced by CSQAH. Laser scanning confocal microscope and Fluo-3/AM staining were utilized to detect the Ca2+ concentration in the HepG2 cells. A microplate reader was used to measure the changes in Ca2+-Mg2+-ATP enzyme. Then, flow cytometry was applied to analyze the activity of ROS and the expression levels of Bcl-2 and Bax. As a result, different concentrations of CSQAH increased the concentration of Ca2+ in the cytoplasm in a dosage-dependent manner. CSQAH decreased the Ca2+‑Mg2+‑ATPase activity in the HepG2 cells. The levels of ROS in the CSQAH groups were significantly higher than the level in the control group. Flow cytometric analysis showed that the Bcl-2 expression levels in the CSQAH-treated groups were downregulated, while Bax expression levels were upregulated, and the effects were dosage-dependent. The regulatory mechanism of HepG2 cell apoptosis induced by CSQAH involved the increase in Ca2+ concentration and ROS levels, a decrease in Ca2+-Mg2+-ATPase activity in the HepG2 cells, and downregulation of anti-apoptotic Bcl-2 expression, and upregulation of apoptotic Bax expression. In summary, the present study demonstrated the antioxidant and antitumor activities of CSE which may suppress tumor growth and alleviate the side-effects of DOX, which may facilitate tumor treatment in a dual manner.

Effect of vitamin D on free radical metabolism in renal tissues of septic rats / Septik ratların böbrek dokularında serbest radikal metabolizmasına vitamin D’nin etkisi

Abstract Objective: Sepsis is a common cause of morbidity and mortality in the intensive care unit. Lipopolysaccharide (LPS)-induced excessive immune response is associated with multi-organ damage in sepsis. Excessive immune response causes multi-organ damage by increasing oxidative stress. Studies on the antioxidant effects of vitamin D demonstrated its protective role. In this study we aimed to investigate the effects of vitamin D on free radical metabolism in LPS injected rats. Methods: Twenty four wistar albino rats were separated into control, sepsis, sepsis+vitamin D and vitamin D groups. Sepsis was induced with single injection of LPS Esherichia coli (O111-b4) 16 mg/kg. Vitamin D was given 2 mg/kg 25 (OH) single dose via gavage for 3 days. Renal function tests were analyzed in serum. Tissue catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione-S-transferase (GST) activities were analyzed, and rat renal tissues were evaluated histopathologically. Results: SOD and GSH-Px activities were not significantly different between the groups. CAT activities were significantly decreased in all groups compared to control, this suppression was seen in the sepsis+vitamin D group versus sepsis group. GST activities were significantly decreased in sepsis and sepsis+vitamin D group compared to control, but GST activities were significantly elevated vitamin D group compare to sepsis and sepsis+vitamin D group. Blood urea nitrogen (BUN) and creatinine levels were significantly elevated in sepsis and sepsis+vitamin D group. Inflammation, expansion in bowman capsule were detected in sepsis and sepsis+vitamin D groups. Conclusion: Vitamin D treatment does not seem to have protective role against renal toxicity in sepsis.Nutrition with vitamin D in sepsis may have suppressive effect on antioxidant enzymes such as CAT and GST due to reduced substrat level which use hydrogen peroxide (H2O2) and GSH as a substrate.

Roles of catalase and glutathione peroxidase in the tolerance of a pulmonate gastropod to anoxia and reoxygenation.

Humans and most mammals suffer severe damage when exposed to ischemia andreperfusion episodes due to an overproduction of reactive oxygen species (ROS). In contrast, several hypoxia/anoxia-tolerant animals survive very similar situations. We evaluated herein the redox metabolism in the anoxia-tolerant land snail Helix aspersa after catalase inhibition by 3-amino-1,2,4-triazole (ATZ) injection during a cycle of wide and abrupt change in oxygen availability. The exposure to anoxia for 5h caused a change of only one of several parameters related to free radical metabolism: a rise in selenium-dependent glutathione peroxidase (Se-GPX) activity in muscle of both saline- and ATZ-injected animals (by 1.9- and 1.8-fold, respectively). Catalase suppression had no effect in animals under normoxia or anoxia. However, during reoxygenation catalase suppression kept high levels of muscle Se-GPX activity (twofold higher than in saline-injected snails up to 30min reoxygenation) and induced the increase in hepatopancreas SOD activity (by 22%), indicating higher levels of ROS in both organs than in saline-injected animals. Additionally, catalase-suppressed snails showed 12% higher levels of carbonyl protein-a sign of mild oxidative stress-in muscle during reoxygenation than those animals with intact catalase. No changes were observed in glutathione parameters (GSH, GSSG and GSSG:GSH ratio), TBARS, and GST activity in any of the experimental groups, in both organs. These results indicate that catalase inhibition inflicts changes in the free radical metabolism during reoxygenation, prompting a stress-response that is a reorganization in other enzymatic antioxidant defenses to minimize alterations in the redox homeostasis in land snails.

Glutathionists in the battlefield of gamma-glutamyl cycle

The critical finding of our work showed that the major role of gamma-glutamyl transferase is to hydrolyze GSH and related gamma-glutamyl peptides to form free amino acids and cysteine-S-conjugates on the apical membranes of cells of various tissues and basolateral membranes of the kidney and that the resulting metabolites are transported into cells to synthesize GSH and mercapturic acids. We also showed that GSH and its S-conjugates of xenobiotics are actively secreted from cells into the circulation and/or lumenal space of the liver. The excretory transport and extracellular hydrolysis of GSH and its S-conjugates of various metabolites by gamma-glutamyl transferase and related peptidases followed by absorption of the hydrolyzed amino acids to synthesize GSH forms intra-organ and inter-organ cycles for GSH metabolism in the liver, kidney, pancreas, small intestine and other tissues that have gamma-glutamyl transferase. The series of our experiments with Helmut showed that gamma–glutamyl cycle proposed by Alton Meister does not function as the putative amino acid transporter but plays critical role in the regulation of redox metabolism of toxic free radicals and xenobiotics.

Epigenetic Regulatory Effect of Exercise on Glutathione Peroxidase 1 Expression in the Skeletal Muscle of Severely Dyslipidemic Mice.

Exercise is an effective approach for primary and secondary prevention of cardiovascular diseases (CVD) and loss of muscular mass and function. Its benefits are widely documented but incompletely characterized. It has been reported that exercise can induce changes in the expression of antioxidant enzymes including Sod2, Trx1, Prdx3 and Gpx1 and limits the rise in oxidative stress commonly associated with CVD. These enzymes can be subjected to epigenetic regulation, such as DNA methylation, in response to environmental cues. The aim of our study was to determine whether in the early stages of atherogenesis, in young severely dyslipidemic mice lacking LDL receptors and overexpressing human ApoB100 (LDLR-/-; hApoB+/+), exercise regulates differentially the expression of antioxidant enzymes by DNA methylation in the skeletal muscles that consume high levels of oxygen and thus generate high levels of reactive oxygen species. Expression of Sod2, Txr1, Prdx3 and Gpx1 was altered by 3 months of exercise and/or severe dyslipidemia in 6-mo dyslipidemic mice. Of these genes, only Gpx1 exhibited changes in DNA methylation associated with dyslipidemia and exercise: we observed both increased DNA methylation with dyslipidemia and a transient decrease in DNA methylation with exercise. These epigenetic alterations are found in the second exon of the Gpx1 gene and occur alongside with inverse changes in mRNA expression. Inhibition of expression by methylation of this specific locus was confirmed in vitro. In conclusion, Gpx1 expression in the mouse skeletal muscle can be altered by both exercise and dyslipidemia through changes in DNA methylation, leading to a fine regulation of free radical metabolism.

Intermittent exercise improves the vasoreactivity of the thoracic aorta in rats.

Vasoreactivity is the most basic and direct indicator to reflect the artery vascular functional state in the body. The majority of previous studies have shown that a high-fat diet (HD) is often associated with a variety of cardiovascular diseases. However, the type of exercise that improves vasoreactivity, as is induced by a HD, remains to be elucidated. In the present study, the effects of aerobic moderate-intensity intermittent exercise through swimming were investigated on thoracic aorta vascular ring contraction and free radical metabolism using Sprague-Dawley rat models of common diet (CD; 23 g protein, 49 g carbohydrate, 4 g fat, 5 g fiber, 7 g bone meal and 6 g vitamins per 100 g), HD (peanuts, milk chocolate and sweet biscuits, in a weight ratio of 3:2:2:1), CD with intermittent exercise (CIE) and HD with intermittent exercise (HIE). The food utilization rate in the swimming group (CIE) decreased in comparison with the CD group. Lee's index in the CIE group decreased in comparison to that of CD after 8 weeks (P<0.05) and also HIE decreased compared to HD (P<0.05) after 8 weeks. Compared with the HD group, contractile response of the thoracic aortic rings to NA decreased in the HIE group, while high-density lipoprotein cholesterol content increased, total cholesterol, triglycerides and low-density lipoprotein cholesterol decreased (P<0.05); the malondialdehyde (MDA) concentration reduced in the myocardium, but the superoxide dismutase (SOD) level improved (P<0.05). In the HIE group, nitric oxide level was similar to the CD group. Compared with CD, contractile response of the thoracic aortic rings to NA increased in the CIE (P<0.05), the MDA concentration reduced in the myocardium, but the SOD level improved (P<0.05). Tunica media smooth muscle of the thoracic aortic rings in the CIE group arranged more regularly in comparison with the CD group (without swimming training). In conclusion, intermittent exercise improves the thoracic aorta vasoreactivity and function by enhanced antioxidant enzyme activity and reduced free radical generating.

Effects of total soy saponins on free radicals in the quadriceps femoris, serum testosterone, LDH, and BUN of exhausted rats

PurposeThe aim of this study was to investigate the impact of total soy saponins (TS) on the free radical metabolism from the quadriceps femoris muscle, serum testosterone, lactate dehydrogenase (LDH), and blood urea nitrogen (BUN) in rats exercised to exhaustion. MethodsA one-time exhausted treadmill exercise session was used. Sprague-Dawley rats were divided into 4 groups: a control group—animals receiving no TS and no exercise (NTSNE), animals receiving TS but no exercise group (TSNE), animals receiving no TS but exercised to exhaustion group (NTSE), and animals receiving TS and exercised to exhaustion group (TSE). The TSNE and TSE groups were fed TS at a dosage of 20 mg/kg body weight once per day for 2 weeks. The NTSE group was given a placebo, and the NTSNE group was not given any treatment. The NTSE and TSE groups were exercised at speed of 30 m/min on treadmill until exhausted. The exercise time and exercise distance were recorded when the rats became exhausted and the rats were then decapitated and anatomized immediately. A 10% homogenate of the quadriceps femoris tissue was prepared. The levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), glutathione reductase (GR), reduced glutathione (GSH), total antioxidant capacity (T-AOC), LDH, BUN, and serum testosterone were tested. ResultsTS significantly increased the exercise time to exhaustion by 20.62% (p < 0.05). The MDA levels were decreased significantly in the TSNE group than in NTSNE group (p < 0.05); the T-AOC levels increased significantly in the TSNE group than in the other 3 groups (p < 0.01, p < 0.05, p < 0.05). The LDH activity significantly increased in the NTSE group than in TSNE group (p < 0.05). The BUN levels significantly increased in the NTSE group than in the other 3 groups (p < 0.01, p < 0.01, p < 0.05), and significantly increased in the TSE group than in NTSNE and TSNE groups (both p < 0.01). The serum testosterone levels increased significantly in the TSNE group than in the other 3 groups (all p < 0.01). SOD, CAT, GSH-Px, GR, and GSH were not statistically different among the groups. ConclusionTS can significantly improve the exercised rats' serum testosterone level and antioxidant activity in their quadriceps femoris to varying degrees, decrease MDA and serum LDH and BUN levels, increase the exercise time, and delay the occurrence of the fatigue.

Exercise, Free Radical Metabolism, and Aging: Cellular and Molecular Processes

The human aging process is associated with a gradual and cumulative decline in the normal functioning of all major bodily systems. While life expectancy is increasing at an exponential rate, the length of time spent in good health across the lifespan (health-span) is in decline. Exercise and physical activity are widely regarded as important interventions to increase longevity and promote healthy aging and well-being. However, cell damage produced by acute and unaccustomed exercise, as a result of an enhanced production of free radical species, is a recognised phenomenon. While all physiological systems appear responsive to the beneficial effects of exercise, further research is required to understand the relationship between free radical metabolism in cellular and molecular processes affected by exercise in the context of human aging. This special issue contains both review and original research articles which, when combined together, provide an interesting insight into the current state of basic and applied research in free radical metabolism, exercise, and aging. In their review, O. F. Araneda et al. discuss how environmental factors, such as altitude and pollution, as well as different forms of exercise, intensity, and duration, affect pulmonary inflammation and oxidative imbalance. They review literature pertaining to antioxidants as well as prooxidants, in relation to oxidative damage, and they further discuss mediators of the inflammatory response to exercise. Importantly, they investigate the relationship between oxidative/inflammatory variables and the interaction between them. D. J. Flis et al. used a prolonged swimming model in rats to investigate mitochondrial swelling and changes in cholesterol in skeletal muscle and liver. A reduction in mitochondrial cholesterol following exercise is related to the inhibition of mitochondrial swelling, and it was also observed within this study that there was an increase in caveolin-1 concentration in muscle. Although markers of oxidative stress in mitochondria were enhanced, there were no similar changes apparent in liver. The work points to a possible adaptive role of caveolin-1 in rat muscle mitochondria, as a consequence of exercise stress. In the second review of this issue, M. Ross et al. discuss the increased risk of developing cardiovascular disease concurrent with increasing age, with respect to increased and prolonged exposure to oxidative stress. The positive and protective effect of regular exercise, in promoting endothelial homeostasis, which may offset the “vascular ageing” process, is further reviewed. It is suggested that acute strenuous exercise causes changes to the oxidant/antioxidant ratio and tissue inflammation and, in their contribution to this issue, H. Li et al. add to the literature in this area with their report on the acute effect of exercise and the inflammatory response in the myocardium of rats. The rats were exercised using a treadmill running protocol, and they observed a regulatory adaptation of mitochondrial function in rat myocardium in response to acute heavy exercise. Their work further demonstrates that myocardial injury in rats is minimized via a cascade activation of mitophagy, responding to myocardial inflammation, as a result of mitochondrial stress triggered during acute exercise. In the final research article of the issue, A. B. Bigley et al. focus on age, with regard to the effect of latent cytomegalovirus on natural killer cell phenotype and exercise responsiveness in the human model. In response to an acute bout of exercise, they show an increased mobilization of NK-cells, which is thought to be an important component of the “fight or flight” response. They also observed that this response is mediated by age, in reporting an increased proportion of NK-cells expressing the terminal differentiation marker CD57 with advancing years. Additionally, NK-cell mediated immunosurveillance following exercise was reported to be compromised by CMC serostatus irrespective of age. Although there is certainly great diversity in the papers presented in this special issue, we hope the reader will find the contributions both interesting and stimulating. We suggest that this collection of papers will serve to enrich our understanding and knowledge of the relationship between free radical metabolism in cellular and molecular processes affected by exercise in the context of aging. Geraint D. Florida-James Rickie Simpson Gareth Davison Graeme Close

Effect of Rosemary on Myocardium Free Radical Metabolism and Serum Enzyme after Exhaustive Exercise

By setting up the exhaustive swimming rats model, the activity of myocardium SOD, the quantity of MDA and the serum GOT are all valued. The results indicates that after the rats took rosemary, their physical ability improved remarkably; the activity of myocardium SOD appeared superior to the control group; the quantity of MDA turned lower than the control group, which shows that rosemary enjoys much stronger influence on the anti-oxidation and anti-free-adical. Besides, their ability of counteracting the free radical of myocardium jumped to a high level. Furthermore, rosemary can also been used to protect the integrality of myocardium cell membrane; to reduce the escape of enzyme from the cell.

Improvement of thoracic aortic vasoreactivity by continuous and intermittent exercise in high-fat diet-induced obese rats.

The aim of the present study was to explore the effects of continuous and intermittent exercise on the thoracic aortic vasoreactivity and free radical metabolism in rats fed with a high-fat diet (HD). Sprague-Dawley (SD) rats were randomly divided into four groups (n=8, each group): Conventional diet (CD), HD, HD with continuous exercise (HCE) and HD with intermittent exercise (HIE). HCE rats swam once/day for 90 min; HIE rats performed swimming exercises 3 times/day, 30 min each time with an interval of 4 h. In these two groups, the exercise was conducted 5 days a week for 8 weeks. Rats in the CD and HD groups were fed without swimming training. At the end of the exercise, all the rats were sacrificed and the blood, thoracic aorta and myocardium were collected immediately. The thoracic aortic vasoreactivity, the plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), malondialdehyde (MDA) and vascular endothelial nitric oxide synthase (eNOS) gene expression were measured. Compared to the control group, in the HD group the enhanced contractile response of the thoracic aortic rings to noradrenaline (NA) was observed (P<0.01). The levels of TC and LDL (P<0.01) were also increased in serum while the HDL level was reduced without statistical significance. In addition, the MDA content was upregulated in the myocardium, but the SOD level decreased (P<0.01). Furthermore, the expression of vascular eNOS mRNA was reduced (P<0.01). However, following the exercise the contraction of the thoracic aorta vascular rings to NA was reduced in the HCE and HIE groups (P<0.01), and the decreased contractile response was more evident in the HIE group compared to the HCE group (P<0.01). Additionally, in the HCE group the level of TG (P<0.01) was decreased, while the HDL (P<0.01) level was increased. Although the reduction of the TC and LDL level was also observed there was no significant difference compared to the HD group. In the HIE group, the TG, TC and LDL were downregulated while the HDL was enhanced (P<0.01). The TC and LDL levels were decreased more than those of the HCE group; however, there was no significant difference in the TG and HDL levels between these two groups; additionally, in these two exercise groups, the MDA level was decreased in the myocardium (P<0.01) while the SOD level was increased (P<0.01). Furthermore, the expression of eNOS was upregulated (P<0.01), but the increase was much more in the HIE group than that in the HCE group. In conclusion, exercise may attenuate the aggravated contraction induced by NA and improve the activity of the thoracic aorta in obese rats, which may be associated with enhanced antioxidant enzyme activity and reduced free radical generating. Additionally, intermittent exercise is better than the continuous exercise in improving the thoracic aorta vasoreactivity.

Review of acupuncture treatment for perimenopausal syndrome

Objective To summarize the mechanism of acupuncture in treating perimenopausal syndrome (PMS) from the aspects of reproductive endocrinology, immune system, neuroendocrine, the metabolism of free radicals and bone, and the effect of lipid.

Effects of acanthopanax senticosus injection on oxidative stress and apoptosis in the hepatic tissue after hepatic ischemia reperfusion in rats

Objective To investigate the effects of Acanthopanax Senticosus Injection (ASI) on free radical metabolism and apoptosis in the hepatic tissue after hepatic ischemia-reperfusion in rats. Methods A total of 100 rats were randomly divided into 5 groups: a sham operation group, a model group, and groups of high-, medium- and low-dose ASI, 20 rats in each group. Seven days before modeling, the drugs had been given by intraperitoneal injection. The rats in the high-,medium- and low-dose groups were given ASI 40, 80 and 120 mg/kg, respectively, and the rats in the sham operation and model groups were given equivalent volume of normal saline. A rat model of hepatic ischemia reperfusion was induced by partial hepatic pedicle clamping followed by reperfusion. 2 h after reperfusion, the activities of SOD, GSH-Px, GST and the MDA level in the hepatic tissue were determined; the activities of ALT and AST in serum were also determined; the histopathological changes and hepatocyte apoptosis were observed using the HE staining and the TUNEL staining, respectively. Results In comparison with the model group, the activities of SOD (11.16 ± 2.31 U/mg, 10.63 ± 1.92 U/mg vs.7.34 ± 1.78 U/mg; P<0.01 or P<0.05), GSH-Px (15.48 ± 2..91 U/mg, 13.23 ± 1.87 U/mg vs. 10.35 ± 2.04 U/mg; P<0.01 or P<0.05), GST(1.76 ± 0.25 U/mg, 1.55 ± 0.22 U/mg vs. 0.94 ± 0.18 U/mg; P<0.01 or P<0.05) in the hepatic tissue in the ASI high- and medium-dose groups were significantly increased; and the MDA level in the hepatic tissue significantly decreased (4.67 ± 1.24 nmol/mg, 4.93 ± 1.53 nmol/mg vs. 10.29 ± 2.41 nmol/mg); the serum levels of ALT(671.82 ± 338.37 U/L, 803.91 ± 441.63 U/L vs.1 416.22 ± 538.94 U/L; P<0.01 or P<0.05), AST(329.02 ± 161.88 U/L, 417.26 ± 182.37 U/L vs. 751.93 ± 262.75 U/L; P<0.01 or P<0.05) were significantly decreased; the histopathological changes and hepatocyte apoptosis in the ASI high-, medium - and low-dose groups were significantly reduced. Conclusions ASI could effectively attenuate oxidative stress in the, improve the histopathological changes, inhibit hepatocyte apoptosis, and protect against hepatic ischemia reperfusion injury in rats. Key words: Liver diseases; Reperfusion injury; Ci Wu Jia Zhu She Ye; Oxidative stress; Rats

Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity

Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4nm. The results confirmed presence of Ce3+ and O2− vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200μM. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine.

Superoxide Anion Radical Production in the Tardigrade Paramacrobiotus richtersi, the First Electron Paramagnetic Resonance Spin-Trapping Study.

Anhydrobiosis is an adaptive strategy that allows withstanding almost complete body water loss. It has been developed independently by many organisms belonging to different evolutionary lines, including tardigrades. The loss of water during anhydrobiotic processes leads to oxidative stress. To date, the metabolism of free radicals in tardigrades remained unclear. We present a method for in vivo monitoring of free radical production in tardigrades, based on electron paramagnetic resonance and spin-trap DEPMPO, which provides simultaneous identification of various spin adducts (i.e., different types of free radicals). The spin trap can be easily absorbed in animals, and tardigrades stay alive during the measurements and during 24-h monitoring after the treatment. The results show that hydrated specimens of the tardigrade Paramacrobiotus richtersi produce the pure superoxide anion radical ((•)O2(-)). This is an unexpected result, as all previously examined animals and plants produce both superoxide anion radical and hydroxyl radical ((•)OH) or exclusively hydroxyl radical.

HEPATOPROTECTIVE EFFECTS ETHANOL EXTRACT OF MAGROVE PROPAGULE (Rhizophora mucronata) IN WHITE RAT STRAIN Sprague Dawley INDUCED CARBON TETRACHLORIDE (CCL4)

Prevalence of liver disease more increased. Imfflamation in liver tissue caused by free radical metabolism results of toxic compounds such as alcohol, paracetamol, and carbon tetrachloride (CCL4). Rhizophora mucronata has been higher antioxidant activities and reported as hepatoprotector. This research was aimed to investigate activity of mangrove propagule (R.mucronata) as a hepatoprotector and determined the effect levels of specific liver enzymes, liver MDA, and histopathological studies. Rhizophora mucronata was extracted by ethanol 95% solvent (b:v)(1:5). There were 21 rats randomly divided into 7 following groups (n=3), they were group I allowed fed with standard pellet, group II was positive control induced CCL4 dose 2 ml/kg BW, group III, IV, V, and VI were induced by CCL dose 2 ml/kg BW and given consecutively the mangrove extract 1 mg/kg BW, 5 mg/kg BW, 15 mg/kg BW, and 25 mg/kg BW. Result showed the extract did not affect significantly (p&gt;0.05) to decreased level of AST enzyme and the best value owned of 15 mg/kg BW treatment with AST levels as 187 U/L. In contrast, extract R.mucronata effected significantly different (p&lt;0.05) on ALT levels with the best value in 5 mg/kg BW treatment. R.mucronata did not effect significantly (p&gt;0.05) of MDA level in liver, and decreased with the best result in 5 mg/kg BW treatment. Histopatological studies showed a protective effect and cell recovery of the liver induced CCL4. Keywords: Antoxidant, Hepatoprotective, Mangrove propagule (R.mucronata)

海岸不同生态断带植物根叶抗逆生理变化与其Na+含量的关系

PDF HTML阅读 XML下载 导出引用 引用提醒 海岸不同生态断带植物根叶抗逆生理变化与其Na+含量的关系 DOI: 10.5846/stxb201310032406 作者: 作者单位: 鲁东大学 作者简介: 通讯作者: 中图分类号: 基金项目: 国家973课题(2009CB421303);烟台市科技局资助(2013-2H351) The relationship between concentrations of Na+ and changes of physiological response to salt in the leaves and roots of plants Author: Affiliation: Ludong University Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:以烟台海岸生态断带滨麦(Leymus mollis)和肾叶打碗花(Calystegia soldanella)为材料,在远离高潮线不同位置上取土样和植物材料,通过测定土壤Na+和两植物根叶Na+含量、丙二醛(MDA)含量、抗氧化酶(SOD、POD、CAT)活性和渗透调节物含量,以揭示滨麦和肾叶打碗花根叶中Na+在其适应海岸盐环境中的生理调控机制。结果表明,在高潮线土壤Na+含量最高,滨麦根叶Na+含量较高,两植物根叶中MDA和水分含量、抗氧化酶活力均较低,但渗透调节物含量均较高。随远离高潮线土壤Na+含量下降,滨麦根叶Na+含量下降,而肾叶打碗花根中Na+含量上升,其根叶Na+含量较滨麦分别高637%和319%。同时两植物根叶MDA含量、叶片含水量增加;两植物根中POD和SOD活力增加;两植物根叶可溶性糖和脯氨酸含量下降。但不同生态断带滨麦叶片平均含水量相对较低, MDA含量、POD和CAT和SOD活力、脯氨酸和可溶性糖含量相对较高。在盐土环境中滨麦通过降低Na+的吸收和提高抗氧化酶活力和有机渗透调节物含量维持氧自由基代谢平衡和水分平衡。而肾叶打碗花是泌盐植物,在不同生态断带其叶片Na+含量、平均含水量相对较高,叶MDA含量、POD和CAT活力、脯氨酸和可溶性糖含量均相对较低。泌盐植物的肾叶打碗花依赖根叶中积累的Na+作为无机渗透调节剂维护其离子平衡和水分平衡及正常生长。因此,积累在根叶中的Na+离子既作为无机渗透调节剂维护细胞离子平衡和水分平衡,又引发细胞生理干旱促进有机渗透调节物合成;另外还作为氧自由基诱发剂促使活性氧自由基(ROS)积累,通过积累的ROS激活抗氧化保护酶系统抑制膜脂过氧化、维护氧自由基代谢平衡。海岸沙地土壤中高浓度Na+是海滨滨麦和肾叶打碗花能长期在盐土环境中生存的依靠元素,其对植物的生理调控作用可能是滨麦和肾叶打碗花适应盐土生存的重要生理适应机理。 Abstract:The dominant species of the halophytes Leymus mollis(dune grass) and Calystegia soldanella (beach bindweed) grown in the coastal dunes of the coast of Yantai, China were chosen as materials for this study. Soil and plant materials were sampled from the high tide line, and 10, 20, 30, 40, and 50 metres off the high tide line of the coast. Na+ concentrations, activities of the antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and malondialdehyde (MDA), proline, soluble protein, and sugar contents in the roots and leaves of L. mollis and C. soldanella were determined to understand the role that Na+ accumulation in the roots and leaves played in the physiological adaption to saline environments. Na+ concentration in the soil was highest at high tide line, and declined with distance, with the sharpest decrease between the high tide line and 20 m further inland. L. mollis and C. soldanella both grew between 10 m and 20 m off the high tide line and further inland. At distances close to the high tide line, the roots and leaves of L. mollis had higher Na+ concentrations than did those of C. soldanella;both species had low contents of MDA and water and lower activities of antioxidant enzymes but higher concentrations of the osmoregulatory substances in leaves and roots.Farther from the high tide line, Na+ concentration also increased in the roots of C. soldanella; at 50 m, Na+ was 637% higher in roots and 319% higher in leaves than in those tissues in L. mollis. Far away from the high tide line, the contents of water and MDA increased in the leaves and roots of both plants; the activities of POD and SOD increased in the roots; and the contents of soluble sugar and proline decreased in the roots of both plants. However, at different distances from high tide, L. mollis had lower average water content, higher contents of MDA, proline, and soluble sugar, and higher POD, CAT, and SOD activity. At the saline seashore soil, L. mollis maintained free radical metabolic balance and water balance by controlling Na+ uptake and increasing the activity of antioxidant enzymes and the content of organic osmoregulatory substances. However, C. soldanella is a salt-secreting halophyte with higher Na+ and average water content in its leaves and roots, lower MDA content, activities of POD and CAT, and lower contents of proline and soluble sugar on different locations away from high tide, which indicated that the Na+ accumulated in the leaves and roots of C. soldanella played a very importance role in maintaining ion balance. Na+ accumulated in the roots and leaves of L. mollis and C. soldanella can induce the accumulation of oxygen free radicals to activate the antioxidant enzyme system which in turn would inhibit lipid peroxidation to maintain the balance of oxygen free radical metabolism. Na+ accumulated in the roots and leaves of two plants not only can be an inorganic osmotic adjustment substance to maintain cellular water balance, but plants also can increase organic osmotic adjustment substances such as proline and soluble sugars to maintain water balance. Results imply that Na+ in the leaves and roots of both plants plays a very important role in physiological regulation of the balance of oxygen free radical metabolism and water balance, allowing these two plants to survive seashore saline conditions. 参考文献 相似文献 引证文献

Usha Venkatraj, Vijay Venkatraj

Oxidative stress is a consequence of both normal and abnormal cellular metabolism and is linked to cell proliferation, differentiation and apoptosis leading to the development of human diseases. A common mechanism for chemotherapeutic agents inducing cell death is through the generation of free radicals. Although the exact mechanism of the molecular signalling that it entails is still being worked upon, it is clear that this varies with the stage and type of cancer and the drug and dosage used. We study the response of MCF10A series progressive breast cancer cell lines, in response to Adriamycin and Cyclophosphamide. A targeted set of candidate genes from these pathways that participate in free radical metabolism were evaluated for gene expression. Genes in oxidative stress response pathways were modelled earlier using the multivariate Boolean Network Modelling. We provide evidence that the strategy of using Boolean modelling and laboratory testing of the model, although not a perfect match, has potential to contribute in biology. We present a novel and testable “threshold” model of free radical generation that is dependent on the quantity of free radical generation. Using logic tools like Boolean circuitry, with fine-tuned experiments may serve a useful purpose in designing preclinical chemotherapic protocols.his document gives formatting instructions for authors preparing papers for publication in this journal. All authors must follow the instructions given in this document for the papers to be published.

辛基酚胁迫对雄性泥鳅抗氧化酶及卵黄蛋白原的影响

PDF HTML阅读 XML下载 导出引用 引用提醒 辛基酚胁迫对雄性泥鳅抗氧化酶及卵黄蛋白原的影响 DOI: 10.5846/stxb201306091553 作者: 作者单位: 延安大学生命科学学院,延安大学生命科学学院,延安大学生命科学学院,延安大学生命科学学院,延安大学生命科学学院 作者简介: 通讯作者: 中图分类号: 基金项目: 国家自然科学基金项目(31240076);陕西省自然科学基础研究计划项目(2012JM3012);陕西省高水平大学建设专项资金资助项目(2012SXTS03);陕西省教育厅科学研究项目(2013JK0710);延安市科学技术研究发展计划项目(2012KS-15);延安大学博士科研启动项目(YD2007-112);陕西省生态学重点学科专项;国家大学生科技创新项目(201210719020) Incidence of antioxidant enzymes and vitellogenin induced in male loach (Misgurnus anguillicaudatus) exposed to octylphenol Author: Affiliation: College of Life Science, Yan’an University,,,, Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:为研究辛基酚 (OP) 对雄性泥鳅抗氧化酶活性及血清卵黄蛋白原 (VTG) 含量的影响,将雄性泥鳅分别暴露于4 种不同质量浓度OP(0.12、0.19、0.32、0.52 mg/L)中持续7、14、21 d和28 d,采用试剂盒检测肝脏超氧化物歧化酶(SOD)与过氧化氢酶(CAT)的含量,采用碱不稳定性蛋白结合磷法检测血清 VTG 的含量。结果表明,0.12 mg/L OP 胁迫14 d,肝脏SOD 和CAT 含量均无显著变化,但是随着胁迫剂量增大和时间延长,SOD 和CAT 含量降低极其显著,在0.52 mg/L OP 胁迫28 d 时降到最低水平;泥鳅在0.12 mg/L OP 中暴露7 d 时,血清VTG 含量就有极其显著升高,且随着胁迫剂量增大和时间的延长,VTG 含量呈升高趋势。提示OP 胁迫对SOD 和CAT 活性有显著的抑制作用,并随胁迫剂量增大和时间延长而抑制加剧,造成氧化损伤;OP 胁迫可诱导VTG 合成,并随暴露剂量增大和时间延长而诱导增强,具有明显的雌激素效应,这可能与其氧化损伤有密切关系。 Abstract:Octylphenol (OP), a group of alkylphenol polyethenoxy ethers (APEs), is usually present in polluted water. OP has strong estrogenic activity, is easily concentrated and is difficult for animals to degrade; therefore, it may affect the function of the liver of Misgurnus anguillicaudatus. The antioxidant enzyme system is an important protection mechanism in the body that prevents oxidative damage during metabolism of oxygen free radicals. Although some studies of the toxicity of many phenolic contaminations have been conducted in fish and mammals, few data are currently available regarding the oxidative damage and estrogenic activity of OP in fish. To investigate the damage and activity of M. anguillicaudatus, the median lethal concentration (LC50) of OP for 24, 48, 72 and 96 hours and safe concentration (SC) were calculated by the single factor toxicity test. The LC50 for 24, 48, 72, and 96 hours were 3.26, 2.69, 2.12 and 1.82 mg/L, and the SC was 0.54 mg/L. Based on the SC values, male loaches were exposed to OP at four different concentrations (0.12, 0.19, 0.32 and 0.52 mg/L) and the activities of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) in the liver were determined at 7, 14, 21 d and 28 d. Additionally, the levels of serum vitellogenin (VTG) were examined by measuring the alkali-labile phosphorus content of the lipid-free protein fraction at 7, 14, 21 d and 28 d. The results showed that the activities of SOD did not differ significantly in response to 0.12 mg/L of OP during 14 d, but that they declined significantly with increased exposure time and concentration, with the lowest activity being observed in response to exposure to 0.52 mg/L of OP for 28 d. The CAT activities showed a similar pattern. When compared to the control group (0 mg/L), the levels of serum VTG increased significantly in response to 0.12 mg/L of OP at 7 d, and increased further with increasing concentration. As the exposure time increased, the total VTG activity in the four concentration groups also increased, with the maximum value being observed in response to exposure to 0.52 mg/L of OP for 28 d. These findings indicated that OP had high toxicity toward M. anguillicaudatus and that moderate and high concentrations of OP were able to induce oxidative stress and exert a significant negative impact on SOD and CAT activities of M. anguillicaudatus. Moreover, the inhibition intensified remarkably as the exposure concentration and time increased, resulting in the hepatic defense function of antioxidant enzymes being reduced. This, in turn, caused excess reactive oxygen species (ROS) accumulation, which can lead to oxidative damage of M. anguillicaudatus. The serum VTG could be induced in male loaches treated by OP and the induction intensified greatly with exposure, indicating that OP possesses estrogenic activity that intensified as the exposure concentration and time increased, leading to damage to the reproductive system of M. anguillicaudatus. These results indicate that the estrogenic effect of OP may be closely correlated with oxidative damage in M. anguillicaudatus. 参考文献 相似文献 引证文献