<Emphasis Type="Italic">Emblica officinalis</Emphasis> Exerts Antihypertensive Effect in a Rat Model of DOCA-Salt-Induced Hypertension: Role of (p) eNOS,NO and Oxidative Stress

Emblica officinalis (EO) has antioxidant properties that could improve redox-sensitive vascular, cardiac and renal changes associated with deoxycorticosterone acetate/1% NaCl high salt (DOCA/HS)-induced hypertension. We determined whether hydroalcoholic lyophilized extract of EO may influence DOCA/HS-induced hypertension by modulating activity of (p) eNOS and endogenous antioxidants. Hypertension was induced in rats by DOCA-salt (20 mg/kg, s.c.) twice weekly for 5 weeks and replacing drinking water with 1% NaCl solution. These rats received cotreatment of different doses of EO (75, 150 and 300 mg/kg/day) for 5 weeks. EO significantly decreased arterial blood pressure and heart rate along with cardiac and renal hypertrophy in a dose-dependent fashion as compared to DOCA control rats. Increased TBARS and decreased endogenous antioxidants including GSH, SOD and GSHPx activity in serum, heart and kidney tissues of hypertensive rats were also normalized. Furthermore, this antihypertensive activity of EO was also linked with increased serum NO, K⁺ levels and decreased Na⁺ levels. Moreover, EO robustly increased activated eNOS expression in heart. Our results demonstrate that EO reduces oxidative stress, prevents development and progression of hypertension as well as cardiac and renal hypertrophy in DOCA/HS-induced hypertension via modulation of activated eNOS, endogenous antioxidants, serum NO and electrolyte levels.     

Increased Lipid Peroxidation of Erythrocytes in Blood Stored in Polyvinyl Chloride Blood Storage Bags Plasticized with Di-[2-Ethyl Hexyl] Phthalate and Effect of Antioxidants

Background and Objectives : Previous work in this laboratory has shown significant decrease in vitamin E in erythrocytes in blood stored in polyvinyl chloride (PVC) bags plasticized with di-[2-ethyl hexyl] phthalate (DEHP), and in erythrocytes incubated in vitro with DEHP. Since vitamin E is a major antioxidant, a study was carried out to find out whether this decrease observed in vitamin E has an effect on lipid peroxidation in blood stored in DEHP-plasticized PVC blood bags. Materials and Methods : Blood was collected in Penpol blood storage bags (which is a DEHP-plasticized PVC bag) and parameters of lipid peroxidation, i.e. activity of superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, concentration of malondialdehyde (MDA), conjugated dienes, hydroperoxides, glutathione and vitamin E studied in erythrocytes after various periods of storage as compared to glass bottles. Erythrocytes were also incubated in vitro with DEHP with and without vitamin E, and changes in lipid peroxidation studied. Results :Blood stored in Penpol bags showed increased lipid peroxidation in erythrocytes as compared to that stored in glass bottles, as is evident from a greater increase in MDA and a greater decrease in glutathione and a significant decrease in vitamin E. The addition of vitamin E decreased the formation of MDA and conjugated dienes and prevented the decrease in vitamin E. However in spite of increased lipid peroxidation in the presence of DEHP, the release of K⁺ and hemoglobin from erythrocytes was lower. When there was an increase in DEHP taken up by erythrocytes, there was a corresponding decrease in vitamin E. More important, whenever there was an increase in vitamin E in erythrocytes (when RBCs in the presence of DEHP were incubated with vitamin E), there was a progressive decrease in DEHP. Conclusion : DEHP caused increased lipid peroxidation in erythrocytes. At the same time, it decreased the release of K⁺ and hemoglobin from erythrocytes. It is possible that the stabilizing effect of DEHP on the erythrocyte membrane may offset the detrimental effects of the increased lipid peroxidation it causes.     

肿瘤坏死因子与疟性贫血

本文以化学发光法（ＣＬ）、诱化学发光法（ＩＣＬ）、红细胞变形性（ＥＤ）检测等方法研究了感染伯氏疟原虫ＡＮＫＡ株的ＢＡＬＢ／ｃ小鼠在注射重组肿瘤坏死因子（ｒＴＮＦ）以后发生严重疟性贫血时，其血浆中活性氧（ＲＯＳ）、相关自由基与ＥＤ及ＥＤ与疟性贫血间的关系。结果发现在严重疟性贫血时动物血浆中ＲＯＳ及相关自由基水平明显增高，ＥＤ明显降低。使用抗氧化剂可以明显改善上述过程而使血红蛋白（Ｈｂ）指数回升。因此认为，疟原虫感染时宿主体内过量肿瘤坏死因子（ＴＮＦ）的产生可使吞噬细胞释放大量ＲＯＳ及相关自由基，血浆中这类物质的大量聚集使红细胞变形能力受到破坏，这样，红细胞很易于被机体的红细胞清除系统所清除，这可能是疟性贫血发生和加重的又一主要途径。     

Effects of various degrees of oxidative stress induced by intermittent hypoxia in rat myocardial tissues

Background and objective: The aim of this study was to investigate the mechanism by which oxidative stress induced by chronic intermittent hypoxia (IH) causes myocardial damage in obstructive sleep apnoea syndrome. Methods: A total of 160 Wistar rats were divided into five experimental groups and subjected to chronic IH with different concentrations of oxygen (5%, 7.5%, 10% IH groups; 10% continuous oxygen and normoxia control groups). Eight rats from each group were sacrificed at the 2‐, 4‐, 6‐ and 8‐week time points. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels and total anti‐oxidant capability (T‐AOC) were measured in supernatants of heart homogenates. Expression of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22^phox and NOX2, and thioredoxin‐2 (Trx‐2) genes were determined by measuring messenger RNA (mRNA) levels by real‐time polymerase chain reaction. Results: Compared with the control groups, MDA levels increased over time in the IH groups, whereas T‐AOC and SOD activity decreased over time. MDA, T‐AOC and SOD activity peaked at 6 weeks into the IH treatment. The 5% IH group showed significantly higher expression of p22^phox and thioredoxin‐2 mRNA, as compared with the other IH groups, as well as the control groups. Conclusions: The severity of oxidative stress induced by chronic IH in myocardial tissue was significantly correlated with the degree of IH. NADPH oxidase and Trx‐2 are important mediators of oxidative stress induced by IH.     

Modulatory action of adenosine on gastric function and ethanol-induced mucosal damage in rats

This study examines the gastric effects of adenosine and its antagonist, theophylline, on secretory function, mucosal blood flow, and on ethanol-induced glandular mucosal damage in rats that were fasted for 24 hr before experimentation. The animals were anesthetized with sodium pentobarbitone (50 mg/kg intraperitoneal) and their tracheae cannulated. An ex vivo stomach chamber then was prepared. The luminal bathing solution was collected every 15 min and the concentrations of H⁺ and Na⁺ were determined by a pH autotitrator and an ionmeter, respectively. The glandular mucosal blood flow was measured by a laser Doppler flowmeter and the severity of lesions was determined by measuring the hemorrhagic areas. Adenosine administration (2.5 or 7.5 mg/kg, subcutaneous) markedly lowered the H⁺ and Na⁺ output but increased the secretory volume and mucosal blood flow in a dose-dependent manner. The same doses of the nucleoside also prevented ethanol-induced mucosal damage. These effects were prevented by pretreatment with theophylline (30 or 60 mg/kg, subcutaneous). Ethanol given alone significantly depressed the H⁺ and Na⁺ secretion. Both effects were not modified by adenosine treatment. However, the depressive action of ethanol on mucosal blood flow was prevented by adenosine. These findings indicate that adenosine modulates the physiological function of the stomach. It also directly activates the defensive mechanism of the stomach, which is partially mediated by the improvement of the gastric mucosal blood flow and an increase in the nonacid component of gastric secretion.     

Neuroprotective and Anti-ageing Effects of Curcumin in Aged Rat Brain Regions

This study investigated the influence of chronically administered curcumin on normal ageing-related parameters: lipid peroxidation, lipofuscin concentration and intraneuronal lipofuscin accumulation, activities of the enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and Na⁺, K⁺, -adenosine triphosphatase (Na⁺, K⁺, -ATPase) in different brain regions (cerebral cortex, hippocampus, cerebellum and medulla) of 6- and 24-month-old rats. In normal ageing, lipid peroxidation and lipofuscin concentration were found to increase with ageing, the activities of SOD, GPx and Na⁺, K⁺, -ATPase, however, decreased with ageing. Chronic curcumin treatment of both 6 and 24 months old rats resulted in significant decreases in lipid peroxide and the lipofuscin contents in brain regions, the activities of SOD, GPx and Na⁺, K⁺, -ATPase however, showed significant increase in various brain regions. The present study, thus, demonstrated the antioxidative, antilipofusinogenesic and anti-ageing effects of curcumin in the brain.     

Some Properties of Erythrocyte Na+ -K+ -ATPase in Essenial Hypertension

The activity and some allosteric properties of Na⁺ -K⁺ -ATPase in erythrocytes and their membrane preparations (ghosts) from 57 patients with essential hypertension and 36 normotensive controls were studied. To reveal enzyme activity in whole erythrocytes the cells were pretreated with detergent Tween-20. It was found that in the patient erythrocytes the Na⁺ -K⁺ -ATPase activity was 33% less as compared to the control group. Moreover, in the patient erythmcytes the sensitivity of the enzyme to high concentrations of MgCI₂ was decreased. In contrast, no analogous changes of the enzyme were revealed in the patient ghosts. It is suggested that the erythrocytes of patients with essential hypertension contain an inhibitor of Na⁺ -K⁺ -ATPase.     

Pomegranate (<Emphasis Type="Italic">Punica granatum</Emphasis> L.) Juice Supplementation Attenuates Isoproterenol-Induced Cardiac Necrosis in Rats

The aim of the present study was to evaluate the efficacy of pre-supplementation with pomegranate (Punica granatum L.) juice (PJ) on heart weight, infarct size, plasma marker enzymes of cardiac damage, lipid peroxidation, endogenous enzymatic and non-enzymatic antioxidants, cardiac ATPases and histopathology of isoproterenol (IP)-induced cardiac necrosis (CN) in rats. Rats treated with IP (85 mg/kg, s.c.) for 2 days at an interval of 24 h caused significant (P < 0.05) infarct in myocardium and increase in heart weight, lipid peroxidation (LPO), activity levels of Ca⁺² ATPase and plasma marker enzymes, while there was significant (P < 0.05) decrease in endogenous enzymatic and non-enzymatic antioxidants and Na⁺-K⁺ and Mg⁺²ATPases. Pre-supplementation with PJ for 30 consecutive days and treated with IP on days 29th and 30th showed significantly (P < 0.05) lesser increase in heart weight, infarct size, plasma marker enzymes, lipid peroxidation, Ca⁺² ATPase and a significant protective effect in endogenous enzymatic and non-enzymatic antioxidants, Na⁺-K⁺ and Mg⁺² ATPases compared to IP alone treated group. Present study provides first scientific report on protective effect of supplementation of Pomegranate juice against IP-induced CN in rats.     

Regulation of Renal Ouabain-Resistant Na+-ATPase by Leptin,Nitric Oxide,Reactive Oxygen Species,and Cyclic Nucleotides: Implications for Obesity-Associated Hypertension

This study examined the effect of leptin on renal ouabain-resistant Na⁺-ATPase, which drives the reabsorption of about 10% of sodium transported in the proximal tubule. Chronic leptin administration (0.25 mg/kg s.c. twice daily for seven days) increased Na⁺-ATPase activity by 62.9%. This effect was prevented by the coadministration of superoxide dismutase mimetic, tempol, or the NADPH oxidase inhibitor, apocynin (2 mM in the drinking water). Acutely administered NO donors decreased Na⁺-ATPase activity. This effect was abolished by soluble guanylate cyclase inhibitor, ODQ, but not by protein kinase G inhibitors. Exogenous cGMP reduced Na⁺-ATPase activity, but its synthetic analogues, 8-bromo-cGMP and 8-pCPT-cGMP, were ineffective. The inhibitory effect of NO donors and cGMP was abolished by EHNA, an inhibitor of cGMP‐stimulated phosphodiesterase (PDE2). Exogenous cAMP analogue and dibutyryl-cAMP increased Na⁺-ATPase activity and abolished the inhibitory effect of cGMP. Finally, the administration of superoxide-generating mixture (xanthine oxidase+hypoxanthine) increased Na⁺-ATPase activity. The results suggest that nitric oxide decreases renal Na⁺-ATPase activity by stimulating cGMP, which in turn activates PDE2 and decreases cAMP concentration. Increased production of reactive oxygen species may lead to the elevation of Na⁺-ATPase activity by scavenging NO and limiting its inhibitory effect. Chronic hyperleptinemia is associated with increased Na⁺-ATPase activity due to excessive oxidative stress.     

Isoform-specific alterations in cardiac and erythrocyte Na ,K-ATPase activity induced by norepinephrine

Background: Myocardial Na⁺,K⁺-ATPase activities are decreased in congestive heart failure because of an increase in plasma norepinephrine levels, but it is difficult to monitor the activities in the clinical setting.Methods and Results: This study investigated whether erythrocyte Na⁺,K⁺-ATPase activity can reflect myocardial enzyme activity and whether isoform-specific alterations occur in the presence of catecholamine. Na⁺,K⁺-ATPase activity was measured by the colorimetric method by using the left ventricular myocardium and erythrocytes prepared from eight rabbits given norepinephrine for 7 days and from eight control rabbits that received saline. The protein levels of total catalytic subunit and α₁ - or α₃-isoform of Na⁺,K⁺-ATPase were determined by Western blot analysis. Na⁺,K⁺-ATPase activity was lower in both myocardium and erythrocytes from norepinephrine-treated rabbits than control rabbits (P < .01 and P < .01, respectively). There was a close correlation in Na⁺,K⁺-ATPase activity between myocardium and erythrocytes (r = .963). Total catalytic subunit protein level was lower in myocardium from norepinephrine-treated rabbits than control rabbits, but the α₁-isoform level was similar between the two groups. The α₃-isoform level was lower in norepinephrinetreated rabbits than control rabbits. In erythrocytes, α₁-isoform was lower in norepinephrinetreated rabbits than control rabbits.Conclusions: Na⁺,K⁺-ATPase activity in myocardium could be reflected in erythrocyte membrane, although there was a difference in isoform-specific regulation between the two.     

Melatonin improves cardiovascular function and ameliorates renal, cardiac and cerebral damage in rats with renovascular hypertension

Abstract:  The effect of melatonin was investigated in an angiotensin II-dependent renovascular hypertension model in Wistar albino rats by placing a renal artery clip (two-kidney, one-clip; 2K1C), while sham rats did not have clip placement. Starting either on the operation day or 3 wk after the operation, the rats received melatonin (10 mg/kg/day) or vehicle for the following 6 wk. At the end of the nineth week, after blood pressure (BP) and echocardiographic recordings were obtained, plasma samples were obtained to assay lactate dehydrogenase (LDH), creatine kinase (CK), antioxidant capacity (AOC), asymmetric dimethylarginine (ADMA), and nitric oxide (NOx) levels. In the kidney, heart and brain tissues, malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) and Na⁺-K⁺ ATPase activities were determined. 2K1C caused an increase in BP and left ventricular (LV) dysfunction. In hypertensive animals LDH, CK, ADMA levels were increased in plasma with a concomitant reduction in AOC and NOx. Moreover, hypertension caused a significant decrease in tissue SOD, CAT, and Na⁺, K⁺-ATPase activities and glutathione content, while MDA levels and MPO activity were increased in all studied tissues. On the other hand, both melatonin regimens significantly reduced BP, alleviated oxidative injury and improved LV function. In conclusion, melatonin protected against renovascular hypertension-induced tissue damage and improved cardiac function presumably due to both its direct antioxidant and receptor-dependent actions, suggesting that melatonin may be of therapeutic use in preventing oxidative stress due to hypertension.     

Potassium Loss and Cellular Dehydration of Stored Erythrocytes following Incubation in Autologous Plasma: Role of the KCI Cotransport System

We studied the regulation of cell volume and cation content in erythrocytes stored at 4°C under blood bank conditions for various lengths of time and subsequently incubated in autologous plasma at 37°C for 4 or 24 h. Cell swelled during storage at 4°C whereas marked K⁺ loss and cell shrinkage were observed when erythrocytes were incubated at 37°C in autologous plasma. The cell shrinkage was inhibited only by the K⁺Cl^- cotransport-specific inhibitor, [(dihydroindenyl)oxy] alkanoic acid, and not by other specific inhibitors of cation transport systems such as ouabain (Na⁺-K⁺ ATPase pump), bumetanide (Na⁺-K⁺-Cl^- cotransport) or carbocyanine (Ca⁺⁺-activated K⁺ channel). Acidification and swelling of the erythrocytes are well known to be able to activate the K⁺Cl^- cotransport; such conditions, which were demonstrated to occur during the storage, could lead to activation of the K⁺Cl^- cotransport in reinfused cells. These data strongly support the evidence that K⁺Cl^- cotransport plays a role in K⁺ loss and dehydration of stored erythrocytes, when incubated in autologous plasma.     

Low G preconditioning reduces liver injury induced by high +Gz exposure in rats

AIM: To investigate the effect of repeated lower +Gz exposure on liver injury induced by high +Gz exposure in rats.METHODS: Sixty male Wister rats were randomly divided into a blank control group, a low G preconditioning group (LG) (exposed to +4 Gz/5 min per day for 3 d before +10 Gz/5 min exposure), and a +10 Gz/5 min group (10G) (n = 20 in each group). Blood specimens and liver tissue were harvested at 0 h and 6 h after +10 Gz/5 min exposure. Liver function was analyzed by measuring serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and liver injury was further assessed by histopathological observation. Malondialdehyde (MDA), superoxide dismutase (SOD) and Na⁺-K⁺-ATPase were determined in hepatic tissue.RESULTS: The group LG had lower ALT, AST, and MDA values at 0 h after exposure than those in group 10G. SOD values and Na⁺-K⁺-ATPase activity in the LG group were higher than in group 10G 0 h post-exposure. Hepatocyte injury was significantly less in group LG than in group 10G on histopathological evaluation.CONCLUSION: It is suggested that repeated low +Gz exposure shows a protective effect on liver injury induced by high +Gz exposure in rats.     

Parameters of oxidative stress in children with Type 1 diabetes mellitus and their relatives

Oxidative stress (OS) plays an important role in the pathogenesis of Type 1 diabetes mellitus (DM). The aim of the study was to compare OS parameters in diabetic children and their first-degree relatives. Fifty diabetic children from the West Bohemian Region were examined as well as their 32 siblings (12 Boys and 20 girls) and 65 of their parents during a period of 6 months. Thirty healthy sex- and age-matched children studied before planned surgeries were normal controls for children, 40 healthy adult volunteers were controls for parents. OS parameters were evaluated in all participants of the study (superoxide dismutase, SOD; glutathione peroxidase, GSHPx; plasma antioxidant capacity, AOC; reduced glutathione, GSH; and malondialdehyde, MDA) and also Type 1 DM-associated antibodies (ICA and GADA). The results in diabetic children showed significantly lower GSHPx and AOC and increased MDA when compared with healthy children. Similar findings were found in their siblings but without statistical significance. It is consequently evident that decreased antioxidative protection and simultaneous free radical (FR) overproduction occur in diabetic children and that there is a similar, but not significant, tendency in their siblings. The findings warrant reducing OS in diabetic children and postponing disease onset in susceptible relatives.     

吲哚美辛胃损伤中内皮素、一氧化氮、氧自由基的作用及其与胃动力的关系

目的 :研究吲哚美辛胃损伤中内皮素 (ET)、一氧化氮 (NO)、氧自由基的作用 ,以及胃动力对这种损伤的影响。方法 :雄性DS大鼠随机分 4组 :对照组、吲哚美辛 5mg/kg组、吲哚美辛 2 5mg/kg组、阿托品组 (阿托品 1mg/kg +吲哚美辛 2 5mg/kg)。吲哚美辛灌胃 ,灌胃前 10min阿托品皮下注射。取动脉血测ET、NO、丙二醛 (MDA)、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH Px)水平 ,进行胃形态学观察。结果 :5mg/kg吲哚美辛不引起胃粘膜损伤 ,各检测指标与对照组无差异 ;2 5mg/kg吲哚美辛可引起胃粘膜显著出血性损伤 ,损伤指数为 38 5 7± 12 4 7,病理损伤积分为13 36± 3 37;ET 1和MDA水平升高 (P <0 0 1) ,NO、SOD、GSH Px水平降低 (P <0 0 1,P <0 0 1,P <0 0 5 ) ;阿托品组粘膜损伤较轻 ,损伤指数为 8 71± 3 35 ,病理损伤积分为 3 77± 1 0 4,ET 1含量和对照组无差异 ,MDA水平升高 (P <0 0 5 ) ,NO、SOD含量有所下降 (P <0 0 5 ) ,GSH Px含量无变化。结论 :吲哚美辛所致胃粘膜损伤中 ,ET 1和MDA生成增加起损害作用 ,内源性NO、SOD和GSH Px可清除氧自由基 ,有保护作用 ;阿托品对吲哚美辛所致胃粘膜损伤的保护作用 ,提示胃动力增加在吲哚美辛致溃疡中有重要作用。     

In vitro effects of resveratrol on oxidative stress in diabetic platelets

To evaluate the in vitro effects of resveratrol (RSV) incubation on platelets from compensated and decompensated diabetic patients in order to use it as an adjuvant therapy. The study was performed on 77 diabetic patients and divided into two phases: 29 compensated and 48 decompensated diabetic platelets were analyzed at recruitment (T ₀) and after in vitro RSV incubation (20 μg/ml) for 3 h at 37 °C (T ₁). Lipoperoxide and nitric oxide (NO) levels, superoxide dismutase (SOD) and Na⁺/K⁺ ATPase activities, total antioxidant capacity (TAC), and membrane fluidity tested by anisotropy of fluorescent probes TMA-DPH and DPH were determined. In vitro RSV incubation counteracts oxidative damage associated with diabetes and its complications; it is able to improve platelet function through augmented membrane fluidity and Na⁺/K⁺ ATPase activity; it enhances antioxidant systems’ functionality by increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels in both compensated and decompensated patients. Such platelet functionality enhancement suggests a new method of secondary prevention of complications associated with platelet dysfunction. Being free from one of the major risks associated with many antidiabetic agents, it can be assumed that RSV utilization in the diabetic diet may have a preventive and protective role in the progression of diabetic oxidative damage.     

Suckling Rat Brain Regional Distribution of Na<Superscript>+</Superscript>,K<Superscript>+</Superscript>-ATPase Activity in the In Vitro Galactosaemia: The Effect of L-Cysteine and Glutathione

Inhibition of Na⁺,K⁺-ATPase activity causes edema and cell death in central nervous system. We determined the in vitro effects of galactose-1-phosphate (Gal-1-P), galactitol (Galtol) and galactose (Gal) (mix A = classical galactosaemia) or Galtol and Gal (mix B = galactokinase deficiency galactosaemia), on Na⁺,K⁺-ATPase activity in suckling rat brain frontal cortex, hippocampus or hypothalamus homogenates. Gal-1-P or Galtol alone at different concentrations, significantly inhibited Na⁺,K⁺-ATPase whereas Gal activated the enzyme in all investigated brain regions. Both mix A and mix B inactivated the enzyme by 20–30% (p < 0.001) in all studied areas. L-Cysteine (Cys) and glutathione (GSH) supplementation in mix B not only reversed the enzyme inhibition but also resulted in an activation of 50–60%, (p < 0.001) in all brain areas. Their presence in mix A also activated the inhibited Na⁺,K⁺-ATPase in hippocampus and hypothalamus to a lower degree, whereas Cys reversed the frontal cortex enzyme activity to control value only. These findings indicate that oxidation of the enzyme critical groups may be involved in galactosaemia, producing inhibitory effect. This phenomenon is reversed by antioxidants Cys and GSH, implying that free radicals may be implicated in the observed enzyme inactivation.     

The Protective Effect of L-Cysteine and Glutathione on the Adult and Aged Rat Brain (Na<Superscript>+</Superscript>,K<Superscript>+</Superscript>)-ATPase and Mg<Superscript>2+</Superscript>-ATPase Activities in Galactosemia In Vitro

The aim of this study was to evaluate whether the addition of the antioxidants L-cysteine (Cys) or the reduced glutathione (GSH) could reverse the alterations of brain total antioxidant status (TAS) and the modulated activities of the enzymes (Na⁺,K⁺)-ATPase, and Mg²⁺-ATPase in adult or aged rat brain homogenates induced by galactosemia in vitro. Mixture A [mix. A: galactose-1-phosphate (Gal-1-P, 2 mM) plus galactitol (Galtol, 2 mM) plus galactose (Gal, 4 mM) = classical galactosemia] or mixture B [mix. B: Galtol (2 mM) plus Gal (1 mM) = galactokinase deficiency galactosemia] were preincubated in the presence or absence of Cys (0.83 mM) or GSH (0.83 mM) with adult or aged brain homogenates at 37C for 1 h. TAS and the enzyme activities were determined spectrophotometrically. Mix. A or mix. B preincubation with the adult brain resulted in a significant (Na⁺,K⁺)-ATPase inhibition (–30%) and a Mg²⁺-ATPase stimulation (+300% and +33%, respectively), whereas lower modifications of the enzyme activities (p < 0.001) were found in the aged brain. Gal mixtures decreased TAS by 40% (p < 0.001) and by 20% (p < 0.01) in adult and aged samples, respectively. The antioxidants significantly increased TAS resulting in the reversion of (Na⁺,K⁺)-ATPase inhibition and Mg²⁺-ATPase stimulation by mix. B only. The inhibitory effect of Gal and its derivatives on brain (Na⁺,K⁺)-ATPase and their stimulatory effect on Mg²⁺-ATPase are being decreased with age, probably due to the producion of free radicals. Cys and GSH increased TAS resulting in a reversion of the inhibited (Na⁺,K⁺)-ATPase in both models of the in vitro galactosemia and the stimulated Mg²⁺-ATPase in galactokinase deficiency galactosemia only.     

新疆红树莓果实提取物降压作用及机制的实验研究

目的观察新疆红树莓果实乙酸乙酯提取物(EER)对自发性高血压大鼠(SHR)的降压作用,并从抗氧化角度探讨其降压作用机制,为红树莓的心血管保护作用提供科学依据。方法将32只16周龄雄性SHR随机分为:高血压对照组(SHR组)、EER低剂量组(EERL组)、EER高剂量组(EERH组)和卡托普利组(Cap组);另选8只WKY大鼠为正常血压对照组(WKY组)。采用无创尾压法测量血压,干预5周后检测大鼠NO、内皮素(ET)、MDA水平及总抗氧化能力(T-AOC)和超氧化物歧化酶(SOD)活性。结果与SHR组比较,Cap组、EERL组、EERH组大鼠于预后血压呈不同程度的下降趋势;EERL组大鼠NO、SOD明显升高(P<0.01);EERH组大鼠SOD、T-AOC明显升高(P<0.01),而ET、MDA明显下降(P<0.05)。结论EER对SHR的降压作用可能与其抗氧化作用有关。     

Poor metabolic control and predisposition to hypertension,rather than hypertension itself,are risk factors for nephropathy in type 2 diabetes

Sodium-lithium countertransport (Na⁺/ Li⁺ CT) activity in erythrocytes has been shown to be high in a subset of patients with essential but not secondary hypertension and in type 1 (insulin-dependent) diabetic patients with nephropathy. More recently it has been shown that the presence of a major gene for Na⁺/Li⁺ CT, or another closely linked gene, rather than the actual level of Na⁺/Li⁺ CT, increases the risk of hypertension onset. The aim of the present study was to investigate whether Na⁺/Li⁺ CT activity is associated with hypertension and nephropathy in type 2 (non-insulin-dependent) diabetes. We studied 18 type 2 diabetic patients with normal blood pressure levels (systolic 140 and diastolic 85 mmHg) and albumin excretion rate (15 g/min), 19 type 2 diabetic patients with hypertension (systolic 145 and diastolic 90 mmHg) and a normal albumin excretion rate (15 g/min) and 19 type 2 diabetic patients with an increased albumin excretion rate (20 g/min), irrespective of blood pressure levels. Eighteen normal subjects, matched for sex and age, served as controls. Na⁺/Li⁺ CT activity in erythrocytes was higher in type 2 diabetics with a high albumin excretion rate (486±148 mol/l erythrocytes per hour,P<0.01) and in hypertensive diabetics (410±129,P<0.05), but not in normotensive diabetics (340±141), than in controls (282±96) (mean±SD). Body mass index was higher in diabetics with hypertension and in those with an abnormal albumin excretion rate than in normotensive diabetics and controls. Blood pressure levels were higher in diabetic patients with an increased albumin excretion rate than in normotensive diabetics and controls. Of diabetic patients with a high albumin excretion rate 26% had normal diastolic blood pressure levels. Diabetics with a high albumin excretion rate had higher glycated haemoglobin, cholesterol and triglyceride levels and a longer duration of diabetes than hypertensive diabetics with a normal albumin excretion rate. The association of these clinical features in type 2 diabetes closely resembles that previously reported in type 1 diabetes. A novel finding of the present study is that predisposition to hypertension, as indicated by high Na⁺/Li⁺ CT, seems to confer a susceptibility to the development of renal damage in type 2 diabetes, partially independent of blood pressure levels per se, and that diabetic patients with high Na⁺/Li⁺ CT and hypertension are, to some extent, protected against the development of nephropathy when the metabolic control is tighter and the duration of the disease shorter.