Free Radical Metabolism Research Articles

Measuring Oxygenation In Vivo with MRS/MRI—From Gas Exchange to the Cell

Oxygen plays a major role as a substrate in metabolic processes in numerous signaling pathways, in redox metabolism, and in free radical metabolism. To study the role of oxygen in normal and pathophysiological states, methods that can be used noninvasively are required. This review examines the potential of nuclear magnetic resonance techniques to study tissue oxygenation. It is written from a systems perspective, looking at detection methods with respect to the path that oxygen takes in the mammalian system-from the lungs, through the vascular system, into the interstitial space, and finally into the cell. Methods discussed range from those that are quantifiable, such as the assessment of spin lattice relaxation time in fluorocarbon solutions, to those that are more correlative, such as assessment of lactate and high energy phosphates. Since the methods vary in their site of application, sensitivity, and specificity to the quantification of oxygen, this review provides examples of how each method has been applied. This may facilitate the reader's understanding of how to optimally apply different methods to study specific biomedical problems.

홍화 약침액의 Nitric Oxide에 대한 소거효과

Objectives : Free radical metabolism seems to occupy a remarkably common position in the mechanisms of aging and aging related disease. Oxidative damage to DNA, lipids. proteins and other molecules may contribute to the development of cancer, cardiovascular disease and possibly neurodegenerative disease. This study was designed to find out whether Carthami Flos Herbal-Acupuncture Solution can scavenge Nitric Oxide(NO) or not. SNAP is NO generator. NO concentration was estimated after 2,6, 12 and 24 hrs in no treatment group, after treatment with Vit. C or 1, 10, 100g/m1 of Carthami Flos Herbal-Acupuncture Solution. There was no significant scavenging effect of Carthami Flos Herbal-Acupuncture Solutionon NO after 2 hrs. But there was a significant scavenging effect of Cafhami Flos Herbal-Acupuncture Solution on NO in 10/m1 group after 6hrs. And there was a significant scavenging effect of carthami Flos Herbal-Acupuncture Solution on NO in 1, 10g/ml group after 12, 24 hrs. These results suggest that Carhami Flos Herbal-Acupuncture Solution has scavenging effect on NO. This study shows that Carthami Flos Herbal-Acupuncture Solution can be used for aging related disease and further studies are required to investigate the antioxidative effects of it.

Erxian Tang (二仙汤)—Introduction of a Chinese herbal formula, clinical practice, and experimental studies

Erxian Tang is a Chinese herbal formula developed for the treatment of menopausal syndrome in women. In the past 50 years, EXT has shown positive efficacy in the treatment of many chronic diseases in TCM, involving syndrome types of Shen yin-yang deficiency, yin-deficiency caused yang-flourishing, and disharmony of Chong-Ren meridian. Experimental studies have revealed that EXT has multiple pharmacological actions on such multiple targets as hypothalamus-pituitary-target gland axis, immune function and free radical metabolism, etc.

Selected oxidative stress markers in a South American crocodilian species

Crocodilians and other diving vertebrates experience hypoperfusion and hypoxia of several internal organs during long dives. At the end of a dive, reperfusion of aerated blood may cause a physiologically relevant oxidative stress. In this study, we analyzed selected markers of oxidative stress in eight organs of normoxic Paraguayan caiman (Caiman yacare) captured in the Brazilian Pantanal wetlands during the winter of 2001 (six mature-adult males and eight young-adult males; AD-1 and YA-1 groups, respectively), and during the summer of 2002 (six young-adult males (YA-2 group), ten hatchlings and five embryos). Lipid peroxidation products determined by three different assays were generally highest in brain, liver and kidney (in comparison with all other organs), and lowest in white muscles from the tail and hind legs. Liver and kidney showed the highest levels of carbonyl protein, while brain showed low levels. Intermediate levels of oxidative stress markers were mostly found in the heart ventricles and lung. Differences in oxidative stress markers between AD-1 and YA-1 were organ-specific, showing no age-related correlation. However, most oxidative stress markers in YA-2 organs were either higher than (by 1.4- to 3.7-fold) or not significantly different from respective values in hatchlings organs. This pattern (hatchlings versus young-adults) was confirmed using correlation analysis of individual caiman size versus levels of oxidative damage markers in four organs. The higher level of oxidative stress markers in young-adults possibly relates to the fast growth rate (and thus, increased oxidative metabolic rate) of C. yacare in the first years of life. Differences in oxidative stress markers between YA-1 and YA-2 were also observed and were ascribed to seasonal changes in free radical metabolism. These results in normoxic C. yacare represent the first step towards understanding the age-related physiological oxidative stress of a diving reptile from a seasonally changing wetland environment.

Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training

Exercise causes oxidative stress only when exhaustive. Strenuous exercise causes oxidation of glutathione, release of cytosolic enzymes, and other signs of cell damage. However, there is increasing evidence that reactive oxygen species (ROS) not only are toxic but also play an important role in cell signaling and in the regulation of gene expression. Xanthine oxidase is involved in the generation of superoxide associated with exhaustive exercise. Allopurinol (an inhibitor of this enzyme) prevents muscle damage after exhaustive exercise, but also modifies cell signaling pathways associated with both moderate and exhaustive exercise in rats and humans. In gastrocnemius muscle from rats, exercise caused an activation of MAP kinases. This in turn activated the NF-κB pathway and consequently the expression of important enzymes associated with defense against ROS (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when ROS production was prevented by allopurinol. Thus ROS act as signals in exercise because decreasing their formation prevents activation of important signaling pathways that cause useful adaptations in cells. Because these signals result in an upregulation of powerful antioxidant enzymes, exercise itself can be considered an antioxidant. We have found that interfering with free radical metabolism with antioxidants may hamper useful adaptations to training.

Aqueous extract of the bark of Terminalia arjuna plays a protective role against sodium-fluoride-induced hepatic and renal oxidative stress

Fluoride is an environmental and industrial pollutant. It has already been reported that the accumulation of fluoride can alter the activities of some enzymes involved in the free-radical metabolism and also decrease the activities of some enzymes involved in the antioxidant defense system. In the present study, we have investigated the antioxidative properties of aqueous extract of the bark of Terminalia arjuna (TA) on sodium fluoride (NaF) induced oxidative damages in the livers and kidneys of Swiss albino mice. The mice were treated with 600 ppm NaF for one week in drinking water and the activities of antioxidant enzymes, like superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST), and the levels of non-protein thiol, reduced glutathione (GSH), along with lipid peroxidation in the liver and kidney, were determined. Fluoride administration significantly altered the levels of all of the factors compared to that of normal mice. Dose- and time-dependent studies suggest that the aqueous extract of the bark of TA showed optimum protective activity against NaF-induced oxidative damages at a dose of 40 mg/kg body weight for 10 days. Oral administration of the extract for the specified dose and time followed by NaF treatment (600 ppm) normalized the levels of the hepatic and renal antioxidant enzymes, GSH, and lipid peroxidation significantly to almost normal levels. The effects of a known antioxidant, vitamin E, and a non-relevant agent, bovine serum albumin (BSA), have also been included in the study. In addition, TA extract has been found to possess radical scavenging activity. Combining all of the data, the results suggest that TA might possess a protective role against NaF-induced hepatic and renal oxidative damages, probably via its antioxidant properties.

Effects of oxidative stress on the Dolichol content of isolated rat liver cells

Dolichol, a long-chain polyisoprenoid broadly distributed in all tissues and cellular membranes with unknown function(s), might have a role in free radical metabolism [it accumulates in older tissues and decreases after CCl4 (in liver) or phenylhydrazine (in spleen and liver) administration]. The effects of the NADPH-ADP-Fe system on Dolichol levels in isolated hepatocytes were explored and the time-course of changes was compared with the release of MDA in the incubation medium and the decrease in CoQ 9 and 10 and Vitamin E levels. Results showed that the system increased lipid peroxidation and decreased Dolichol and CoQ levels in_parallel fashions and lowered Vitamin E levels with shorter latency. Meanwhile, no increase in dead cells and no Dolichol release in the medium were detected. In conclusion, an increase in oxidative stress possibly caused a rapid degradation of dolichol by the same (unknown) mechanism responsible for the breakdown of_Ubiquinone isoprenoid chains.

Imbalanced free radicals and antioxidant defense systems in schizophrenia: A comparative study

To examine changes of blood oxidative-antiovidative level in schizophrenic patients and its relationship with clinical symptoms. Forty-six Chinese patients met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV) criteria for schizophrenia and fifty age- and sex-matched healthy controls were enrolled in the present study. Baseline psychiatric symptom severity was assessed with brief psychiatric rating scale, positive and negative syndrome scale on the blood draw day. Fresh blood samples were collected to measure levels of nitric oxide and lipid peroxide in plasma as well as activities of superoxide dismutase, catalase and glutathione peroxidase in red blood cells by spectrophotometric assays simultaneously. Comparison of the biochemical parameters indicated that the level of nitric oxide and lipid peroxide increased in patient group, which represented a positive correlation with positive scale scores; while the activities of three critical enzymes decreased and showed a negative linear correlation. This study showed that there are dysregulation of free radical metabolism and poor activities of the antioxidant defense systems in schizophrenic patients. Excess free radicals formation may play a critical role in the etiology of schizophrenia. Using antioxidants might be an effective therapeutic approach to partially alleviate or prevent the symptoms of schizophrenia.

Effects of repeated desflurane and sevoflurane anesthesia on enzymatic free radical scavanger system

To investigate the possible effects of repeated sevoflurane and desflurane anesthesia on hepatocellular system by evaluating the free radical metabolism, hepatocellular enzymes and histopatholgical changes in rats. Four groups of animals were studied. Sevoflurane 2% (v/v) and desflurane 6% (v/v) in air/O2 were administered to animals in group II (n=9) and III (n=9) respectively. 100% (v/v) O(2) was administered in group IV (n=9). Administration was done for 60 minutes over 3 days. Nine animals were allocated to control group (group I), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GSH-Px), glutathione-s-transferase (GST) and thiobarbituric acid reactive substances (TBARS) were studied. Also electron microscopy was performed. Catalase, SOD, GSH-Px, GST activities and TBARS levels were significantly higher in groups II and III than in group I (p<0.05). All parameters were significantly higher in groups II versus group IV (p<0.05). On the other hand, SOD, GSH-Px and GST activities were significantly elevated in group III than IV, but CAT activity and TBARS levels were not significantly. Catalase, SOD, GSH-Px, GST but not TBARS levels were significantly higher in groups II and III than in group IV (p<0.05). TBARS levels were higher in group III than in group IV, but this elevation was not statistically significant. CAT, SOD and GSH-Px activities were significantly higher in groups II than in group III (p<0.05). Although electron microscopy findings were similar for group II and III, we can conclude that sevoflurane might cause more cellular damage than desflurane by causing higher activation of free radical metabolising enzymes.

Female Infertility and Free Radicals: Potential Role in Adhesions and Endometriosis

Free radicals are highly reactive molecules produced in the cell either as part of, or as end-products of, biochemical reactions that have crucial roles in the homeostasis of the organism. Thus, excess production or impaired elimination of free radicals leads to increased oxidative stress, which has been implicated in the development of several different disease states, including hypoxia-reperfusion injury, cancer, and aging. Peritoneal adhesions and endometriosis are relatively commonly identified in women, and are known to be associated with infertility without clearly understood pathophysiology. The prevention and treatment strategies of these conditions, both of which have tremendous propensity to recur, have not been completely established. The development of both disorders has been shown to be closely related to the presence of increased oxidative stress in the tissues. In this article, we review this relationship with reference to the mechanistic steps involved and their regulation. As our knowledge of both conditions expands, we believe there will be opportunities for specific steps to intervention in free radical metabolism to reduce and/or prevent further development of endometriosis and adhesions.

Effects of Inhalation of Oxygen on Free Radical Metabolism and Oxidative, Antioxidative Capabilities of the Erythrocyte After Intensive Exercise

Two groups, each containing 10 young healthy male students, participated in the study. One group breathed 70% O2 after exercise (70% O2 group) while the other group breathed normal air (Normal air group) after exercise. The results of the study show the following: (1) in both groups, the Monodehydyoxygenbate (MDA) in erythrocyte (RBC) and serum, and superoxide dismutase (SOD) and glutathione Peroxidas (GSH-px) in serum were significantly higher immediately after exercise than at rest; (2) the MDA in RBC and serum were significantly higher in the Normal air group than in the 70% O2 group for 30 minutes after exercise; and (3) the SOD in serum and GSH-px in blood and serum were significantly higher in the 70% O2 group than in the Normal air group for 30 minutes after exercise. We suggest that the effects of inhaling 70% O2 could prevent fatigue from antagonizing free radicals damage, hastening removal of free radicals, which would facilitate recovery from fatigue.

Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function

Reactive oxygen species (ROS) are important mediators of cellular damage and lipid peroxidation is the most important expression of ROS-induced oxidative stress. Recent studies have suggested that increased plasma malondialdehyde (MDA) levels are a consequence of specific immunosuppressive therapies. This study aims at investigating the relation between oxidative stress and immunosuppressive therapies in renal transplant patients with stable renal function and uneventful postoperative course. The study group included 26 renal patients. Two groups of renal transplant recipients, treated with a different combination of immunosuppressive agents were studied (Group A: CyA, MMF, Steroids and Basiliximab, Group B: Tacrolimus, MMF, Steroids and Daclizumab). All patients had an uneventful postoperative course. Plasma MDA levels were measured before transplantation, 1 and 6 months after. Plasma concentration of endogenous creatinine (Cr) was used as a measure of stable renal function. Levels of MDA were increased before the transplantation in all renal patients (MDA: 7.81 +/- 4.81, normal levels: 2.23-4.08 nmol/ml, P < 0.05). Combined therapy with CyA was associated with high values of MDA at 6 months measurement after transplantation. However this tendency of increased MDA levels did not achieve a statistical significance (Group A: 6.97 vs. 9.06 nmol/ml, P>0.05). On the contrary, statistically significant diminution of MDA levels was observed in Group B patients (Tacrolimus-MMF-steroids) at 6 months measurement after transplantation. (Group B: 8.61 vs. 4.11 nmol/ml, P<0.02<0.05). Immunosuppressive combined therapy with CyA was associated with the high values of MDA that were measured posttransplantly. Our study provides strong evidence that Tacrolimus is significantly associated with improved free radical metabolism.

Negative Regulation of Superoxide Dismutase-1 Promoter by Thyroid Hormone

The role of thyroid hormone [L-3,5,3'-triiodothyronine (T3)] and the thyroid hormone receptor (TR) in regulating growth, development, and metabolic homeostasis is well established. It is also emerging that T3 is associated with oxidative stress through the regulation of the activity of superoxide dismutase-1 (SOD-1), a key enzyme in the metabolism of oxygen free radicals. We found that T3 reverses the activation of the SOD-1 promoter caused by the free radical generators paraquat and phorbol 12-myristate 13-acetate through the direct repression of the SOD-1 promoter by liganded TR. Conversely, the SOD-1 promoter is significantly stimulated by unliganded TRs. This regulation requires the DNA-binding domain of the TR, which is recruited to an inhibitory element between -157 and +17 of the SOD-1 promoter. TR mutations, which abolish recruitment of coactivator proteins, block repression of the SOD-1 promoter. Conversely, a mutation that inhibits corepressor binding to the TR prevents activation. Together, our findings suggest a mechanism of negative regulation in which TR binds to the SOD-1 promoter but coactivator and corepressor binding surfaces have an inverted function. This effect may be important in T3 induction of oxidative stress in thyroid hormone excess.

Examination of free radical metabolism and antioxidant defence system elements in patients with obsessive–compulsive disorder

Free radicals and oxidative stress are involved in the pathogenesis of various diseases. Malondialdehyde (MDA) is a natural product of lipid peroxidation in all mammalian cells. Vitamins C and E are nonenzymatic antioxidant structures. Our study investigated the role of free radicals in the obsessive–compulsive disorder (OCD). The participants were 30 patients with OCD that were drug-free at least for a month and a control group of 30 healthy subjects, matched with respect to age and sex. In both groups, the levels of erythrocyte malondialdehyde and the plasma vitamin C and E concentrations were measured. The levels of malondialdehyde were significantly higher in the patient group than in the control group ( p < .01). The levels of plasma vitamin E were significantly lower in the patient than in the control group ( p < .02). Although our patient group had slightly lower concentrations of plasma vitamin C compared to our control group, the difference between these two groups was not statistically significant. There was a significant correlation between increasing malondialdehyde levels and decreasing vitamin E concentrations. This study shows the presence of a significant relationship of OCD and oxidative stress, and consequently, an involvement of free radicals and of the antioxidant defence. Biochemical studies may contribute to the understanding of OCD and its treatment.

Implication du stress oxydant dans la physiopathologie de la schizophrénie : revue de la literature

Background Schizophrenia is a devastating psychiatric disorder with a broad range of behavioural and biologic manifestations. There are several clinical characteristics of the illness that have been consistently associated with poor premorbid adjustment, long duration of psychosis prior to treatment and prominent negative symptoms. The etiopathogenic mechanisms of lack of insight in patients with schizophrenia are to date unknown, although several hypotheses have been suggested. A point of convergence for the theoretical models occurs with regard to the neuronal membrane. Neuronal membrane contains a high proportion of polyunsaturated fatty acid and is the site for oxidative stress. Oxidative stress is a state when there is unbalance between the generation of reactive oxygen species and antioxidant defence capacity of the body. It is closely associated with a number of diseases including Parkinson's disease, Alzheimer-type dementia and Huntington's chorea. Accumulating evidence points to many interrelated mechanisms that increase production of reactive oxygen or decrease antioxidant protection in schizophrenic patients. Objectives This review aims to summarize the perturbations in antioxidant protection systems during schizophrenia, their interrelationships with the characteristic clinics and therapeutics and the implications of these observations in the pathophysiology of schizophrenia are discussed. Literature findings In schizophrenia there is evidence for deregulation of free radical metabolism, as detected by abnormal activity of critical antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase). Many studies conclude in the decrease in the activity of key antioxidant enzymes in schizophrenia. A few studies have examined levels of non enzymatic antioxidants such as plasma antioxidant proteins (albumin, bilirubine, uric acid) and trace elements. How showed decreased levels in schizophrenic patients. Others studies have provided evidence of oxidative membrane damage by examining levels of lipid peroxidation products. Such abnormalities have been associated with certain clinical symptoms and therapeutic features. Negative symptoms have been associated with low levels of GSH-Px. Positive symptoms have been positively correlated with SOD activity. Plasma TAS was significantly lower in drug-free and haloperidol treated patients with schizophrenia. A low erythrocyte SOD activity has been found in never-treated patients, but with haloperidol treatment, SOD activity increased. Discussion These results demonstrate altered membrane dynamics and antioxidant enzyme activity in schizophrenia. Membrane dysfunction can be secondary to free a radical-mediated pathology, and may contribute to specific aspects of the schizophrenia symptomatology. Membrane defects can significantly alter a broad range of membrane functions and presumably modify behavior through multiple downstream biological effects. Phospholipid metabolism in the brain may be perturbed in schizophrenia, with reduced amounts of phosphatidylcholins and phosphatidylethanolamine in post-mortem brain tissue from schizophrenic patients, and large amounts of lipofuscin-like materiel in the oligodendrocytes. The existence of these products within cell membranes results in an unstable membrane structure, altered membrane fluidity and permeability and impaired signal transduction. Recent findings suggest that multiple neurotransmitter systems may be faulty. CNS cells are more vulnerable to the toxic effects of free radicals because they have a high rate of catecholamine oxidative metabolic activity. Neurotransmitters, like glutamate, can induce the same metabolic processes that increase free radical production and can lead to impaired dopamine-glutamate balance. These results question the role of this imbalance in the biochemical basis evoked in the etipathogenic mechanisms of schizophrenia, as well as the role of antioxidants in the therapeutic strategy and their implication in preventive and early intervention approaches in populations at risk for schizophrenia.

Effects of Arsenic (AsIII) on Lipid Peroxidation, Glutathione Content and Antioxidant Enzymes in Growing Pigs

This experiment was conducted to investigate the effect of arsenic (As III ) on lipid peroxidation, glutathione content and antioxidant enzymes in growing pigs. Ninety-six Duroc-Landrace-Yorkshire crossbred growing pigs (48 barrows and 48 gilts, respectively) were randomly assigned to four groups and each group was randomly assigned to three pens (four barrows and four gilts). The four groups received the same corn-soybean basal diet which was supplemented with 0, 10, 20, 30 mg/kg As respectively. Arsenic was added to the diet in the form of As2O3. The experiment lasted for seventy-eight days after a seven-day adaptation period. Malondialdehyde (MDA) levels, glutathione (GSH) contents and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) activities were analyzed in serum, livers and kidneys of pigs. The results showed that pigs treated with 30 mg As/kg diet had a decreased average daily gain (ADG) (p<0.05) and an increased feed/gain ratio (F/G) (p<0.05) compared to the controls. The levels of MDA significantly increased (p<0.05), and the contents of GSH and the activities of SOD, CAT, GPx, GR and GST significantly decreased (p<0.05) in the pigs fed 30 mg As/kg diet. The results indicated that the mechanism of arsenic-induced oxidative stress in growing pigs involved lipid peroxidation, depletion of glutathione and decreased activities of some enzymes, such as SOD, CAT, GPx, GR and GST, which are associated with free radical metabolism. (Asian-Aust. J. Anim. Sci. 2006. Vol 19, No. 5 : 727-733)

L-Propionil Carnitine (LPC) is a Propionic Outcome of Carnitine

L-Propionil Carnitine (LPC) is a propionic derivative of Carnitine. It enhances mitochondrial activity, fat acids and free radical metabolism; it could therefore prove effective in preventing chronic oxidative diseases such as Cavernous fibrosis, which results essentially from an increase in endothelin, and a decrease in nitric oxide (NO) and prostaglandins (PGEi), as it occurs with hypoxia. An incidence of about 15% of segmentary cavernous fibrosis is reported as a consequence of, at least, a 72-hour catheterization. The physiopathology of the syndrome is still uncertain, but strongly related to vasculitis. We carried out a 15-month double-blind, prospective, randomized placebo-control study on 240 patients (age range: 42–68 years) on the possibility of preventing fìbrosis through LPC; study follow-up at 6 months, drug dose: 2g/day p.o. Cavernous fibrosis was reported in 11% of LPC treated patients, and 14% of the placebo group (p = l). Any kind of prevention, even if with poor outcomes as in our experience, should be usefully considered and improved.

NAD(P)H Oxidase and Multidrug Resistance Protein Genetic Polymorphisms Are Associated With Doxorubicin-Induced Cardiotoxicity

A significant number of patients treated with anthracyclines develop cardiotoxicity (anthracycline-induced cardiotoxicity [ACT]), mainly presenting as arrhythmias (acute ACT) or congestive heart failure (chronic ACT). There are no data on pharmacogenomic predictors of ACT. We genotyped participants of the German non-Hodgkin lymphoma study (NHL-B) who were followed up for the development of heart failure for a median of >3 years. Single-nucleotide polymorphisms (SNPs) were selected from 82 genes with conceivable relevance to ACT. Of 1697 patients, 55 developed acute and 54 developed chronic ACT (cumulative incidence of either form, 3.2%). We detected 5 significant associations with polymorphisms of the NAD(P)H oxidase and doxorubicin efflux transporters. Chronic ACT was associated with a variant of the NAD(P)H oxidase subunit NCF4 (rs1883112, -212A-->G; symbols with right-pointing arrows, as edited?' odds ratio [OR], 2.5; 95% CI, 1.3 to 5.0). Acute ACT was associated with the His72Tyr polymorphism in the p22phox subunit (rs4673; OR, 2.0; 95% CI, 1.0 to 3.9) and with the variant 7508T-->A (rs13058338; OR, 2.6; 95% CI, 1.3 to 5.1) of the RAC2 subunit of the same enzyme. In agreement with these results, mice deficient in NAD(P)H oxidase activity, unlike wild-type mice, were resistant to chronic doxorubicin treatment. In addition, acute ACT was associated with the Gly671Val variant of the doxorubicin efflux transporter multidrug resistance protein 1 (MRP1) (OR, 3.6; 95% CI, 1.6 to 8.4) and with the Val1188Glu-Cys1515Tyr (rs8187694-rs8187710) haplotype of the functionally similar MRP2 (OR, 2.3; 95% CI, 1.0 to 5.4). Polymorphisms in adrenergic receptors previously demonstrated to be predictive of heart failure were not associated with ACT. Genetic variants in doxorubicin transport and free radical metabolism may modulate the individual risk to develop ACT.

Effects of chronic brain hypoperfusion on cerebrbral free radical metabolism and learning-memory function

目的 探讨双侧颈总动脉结扎所致的慢性脑低灌注状态下大鼠学习记忆功能及脑组织自由基代谢的时程改变.方法雄性SD大鼠,行双侧颈总动脉结扎术,术后4h、24h、3d、7 d、2周、4周、8周分别取脑组织进行超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量的检测,在脑缺血2周、4周、8周时进行Morris水迷宫实验.结果 Morris水迷宫实验结果表明,各缺血组大鼠在学习记忆功能上较对照组有显著减退,表现在逃避潜伏期[从(8.68±1.32)s延长至(23.95±4.76)s,P＜0.05]和游泳路径[从(171.99±23.12)cm延长至(573.68±124.22)cm,P＜0.01]均明显延长,缺血8周时仍不能恢复,表明双侧颈总动脉结扎所致的慢性脑低灌注状态可引起大鼠学习记忆功能明显下降.自由基代谢相关检测结果表明,缺血4h起,大鼠皮层SOD活性显著降低[从(257.97±10.79)Nu/mg蛋白降至(152.68±38.26)Nu/mg,P＜0.01],MDA含量明显升高[从(2.95±0.34)nmol/mg蛋白升至(5.31±1.68)nmol/mg,P＜0.05],缺血8周时仍不能完全恢复.结论双侧颈总动脉永久结扎后形成的脑部慢性低灌注状态可导致脑组织自由基代谢紊乱,并进一步引起学习记忆功能减退。

Effects of Fluoride Levels on Lipid Peroxidation and Antioxidant Systems of Growing/Finishing Pigs

Malondialdehyde (MDA) and total antioxidant capacity (T-AOC) levels, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), glutathione transferase (GST) and xanthine oxidase (XOD) activities were analyzed in serum, livers and kidneys of pigs treated with graded doses of fluoride (as NaF). Ninety-six Duroc-Landrace-Yorkshire crossbred growing pigs (48 barrows and 48 gilts, respectively), with similar initial weight 24.14±1.12kg, were randomly assigned to four different treatments. These treatments containing the following added F: basal control; 50 mg/kg F; 100 mg/kg F and 150 mg/kg F were randomly assigned to four pens (three barrows and three gilts) each in a completely randomized design. The results showed pigs treated with 150 mg/kg F significantly decreased average daily gain (ADG) (p<0.05) and increased feed/gain ratio (F/G) (p<0.05) compared to the controls. In the groups treated with fluoride, the contents of MDA increased, T-AOC levels and the activities of SOD, GSH-PX, CAT, GST and XOD decreased, and most of which altered significantly (p<0.05). The study therefore indicated the mechanism of excess fluoride on the impairment of soft tissues involved in lipid peroxidation and decreased the activities of some enzymes associated with free radical metabolism. (Asian-Aust. J. Anim. Sci. 2005. Vol 18, No. 4 : 552-556)