Effect of verapamil on focal epileptic activity in the rat cerebral cortex

Experiments were carried out on 64 nonanesthetized male Wistar rats (200-220 g). Epileptic foci were induced by the application of a filter paper saturated with a solution of benzylpenicillin sodium salt (12,000 and 20,000 U/ml) to the sensorimotor cortex. It was shown that subsequent intraperitoneal administration of verapamil (5 mg/kg and 10 mg/kg) during steady focal epileptic activity (EpA) resulted in the suppression of EpA in most animals. The antiepileptic effect of verapamil was manifested in a reduced frequency and amplitude of spike discharges, decreased power of epileptic foci and less frequent appearance of seizure (ictal) discharges. The role of Ca canals of neuronal membranes in the pathogenesis of epilepsy is discussed.     

Possible role of regional superoxide dismutase activity and lipid peroxide levels in cadmium neurotoxicity: in vivo and in vitro studies in growing rats

Cd2+ (0.4 mg/kg) administration to growing rats (45 +/- 5 g) intraperitoneally, daily for 30 days was found to decrease the activity of superoxide dismutase (SOD) in all the brain regions, except hippocampus. The concentrations of lipid peroxides were significantly elevated in the cerebellum, cerebral cortex, corpus striatum and midbrain. A 100% inhibition in SOD activity was observed by 14 microM and 50 microM of Cd2+ in bovine blood and rat brain preparations, respectively. Cadmium-induced strong inhibitory effect on brain and purified bovine blood SOD suggested a direct effect of the metal on enzyme molecule. Furthermore, in vitro addition of a wide range of Cd2+ (1-100 microM) increased the rate of lipid peroxidation (LPO) reaction in fresh brain homogenate, however, did not affect boiled homogenate. The studies on LPO in reconstituted homogenate resulting from mixing of fresh and/or heated different subcellular fractions indicated the presence of some heat-labile Cd2+ -sensitive factor in 15000 x g pellet fraction. It is suggested that Cd2+ directly and indirectly through inhibition of SOD, increases the LPO of cell membranes and thus produces damage to the associated physiological functions leading to central nervous dysfunctions.     

The antiepileptic effects of sodium valproate and the calcium antagonist riodipine when used jointly in a model of focal penicillin-induced epileptic activity]

In experiments on 52 freely moving Wistar male rats, 200-220 g in weight, on the model of focal penicillin-induced epileptic activity (EpA) in brain cortex the efficacy of combined application of drugs influencing different mechanisms of epileptogenesis: sodium valproate enhancing GABA-ergic processes, and the calcium antagonist ryodipine (1,4-dihydropyridine) have been studied. It was shown that valproate and ryodipine when used in combination at relatively small doses (150 and 0.8 mg/kg l.p., respectively) produced a more marked antiepileptic effect than each of these drugs given alone. These and previously reported results of studies on the model of generalized pentylenetetrazol-induced EpA, suggest that complex pathogenic therapy (CPT) as a combination of the antiepileptic drugs acting on the corresponding basic pathogenic mechanisms of respective form of epilepsy is reasonable to be used. CPT allows to obtain a better curative effect with a lower dose of each drug used and to reduce the risk of side effects of the drugs applied at large doses in case of monotherapy.     

Can the function of the extirpated amygdaloid complex be compensated for by the transplantation of embryonic nerve tissue?

In 20 white rats bilateral coagulation of the amygdalar complex was produced; on the fifth day to one half of them transplantation was performed by introducing stereotaxically on the left side 0.2-0.5 mm3 of the brain embryonal tissue from the corresponding area of the amygdala of 20-days embryo; in control saline was administered. After two months the rats were sacrificed to determine the activity of antiradical defense by superoxide dismutase (SOD) and the level of lipids peroxide oxidation (LPO) in the cerebral cortex. The transplantation decreased LPO even more and increased SOD as compared to amygdalectomy, e. i. caused still greater deviations from the norm (in this meaning--paradoxal effect), what apparently corresponds to intensification of adaptative-compensatory processes caused by amygdalectomy. The transplantation did not reverse the rats behaviour to the initial one and did not eliminate memory defect in the test of conditioned reaction of passive avoidance (like pyrazetam); it had different direction influence on "drinking under current" in conflict situation, only in particular cases approaching it to the norm.     

Malathion-induced Oxidative Stress in Rat Brain Regions

Malathion is a pesticide with high potential for human exposure. However, it is possible that during the malathion metabolism, there is generation of reactive oxygen species (ROS) and malathion may produce oxidative stress in intoxicated rats. The present study was therefore undertaken to determine malathion-induced lipid peroxidation (LPO), protein carbonylation and to determine whether malathion intoxication alters the antioxidant system in brain rats. Malathion was administered intraperitoneally in the acute and chronic protocols in the doses of 25, 50, 100 and 150 mg malathion/kg. The results showed that LPO in brain increased in both protocols. The increased oxidative stress resulted in an increased in the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), observed in cortex, striatum in the acute malathion protocol and hippocampus in the chronic malathion protocol. Our results demonstrated that malathion induced oxidative stress and modulated SOD and CAT activity in selective brain regions.     

The effects of oxidative stress in urinary tract infection during pregnancy

The purpose of this study was to determine the effect of urinary tract infection (UTI) on antioxidant systems and lipid peroxidation (LPO) levels during pregnancy. We also investigated if these antioxidant systems and LPO levels differed in each trimester. One hundred forty-three nonpregnant women, as a control group, and 77 pregnant women were included in the study. Urine cultures were performed according to standard techniques. Catalase (CAT), superoxide dismutase (SOD), and LPO levels were measured using a spectrophotometer. UTI was observed in 14 of 77 pregnant women and the isolated microorganisms were Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus. CAT, SOD, and LPO levels were increased in pregnant women compared with nonpregnant women (P<.01). CAT, SOD activities, and LPO levels were increased from the first trimester to the third trimester in pregnancy without UTI. However, CAT and SOD activities were decreased, LPO levels were increased from the first trimester to the third trimester in pregnancy with UTI (P<.01). Pregnancy causes oxidative stress and also UTI during pregnancy may aggravate oxidative stress.     

Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype.

A great number of epidemiological studies have demonstrated that the frequency of the epsilon4 allele of the apolipoprotein E gene (APOE) is markedly higher in sporadic and in familial late onset Alzheimer disease (AD). In the frontal cortex of AD patients, oxidative damage is elevated. We address the hypothesis that the APOE genotype and reactive oxygen-mediated damage are linked in the frontal cortex of AD patients. We have related the APOE genotype to the levels of lipid oxidation (LPO) and to the antioxidant status, in frontal cortex tissues from age-matched control and AD cases with different APOE genotypes. LPO levels were significantly elevated in tissues from Alzheimer's cases which are homozygous for the epsilon4 allele of APOE, compared to AD epsilon3/epsilon3 cases and controls. Activities of enzymatic antioxidants, such as catalase and glutathione peroxidase (GSH-PX), were also higher in AD cases with at least one epsilon4 allele of APOE, while superoxide dismutase (SOD) activity was unchanged. In the frontal cortex, the concentration of apoE protein was not different between controls and AD cases, and was genotype independent. The Ginkgo biloba extract (EGb 761), the neurosteroid dehydroepiandrosterone (DHEA) and human recombinant apoE3 (hapoE3rec) were able to protect control, AD epsilon3/epsilon3 and epsilon3/epsilon4 cases against hydrogen peroxide/iron-induced LPO, while hapoE4rec was completely ineffective. Moreover, EGb 761 and DHEA had no effect in homozygous epsilon4 cases. These results demonstrate that oxidative stress-induced injury and protection by antioxidants in the frontal cortex of AD cases are related to the APOE genotype.     

蛇毒清胶囊对眼镜蛇咬伤局部坏死患者血浆LPO、SOD、GSH-Px的影响

目的观察蛇毒清胶囊对眼镜蛇咬伤合并局部组织坏死患者血浆LPO、SOD、GSH-PX的影响及疗效。方法将眼镜蛇咬伤2 h内合并局部组织坏死的患者60例,随机分为两组,均给予常规治疗,治疗组加服蛇毒清胶囊,均以7天为1疗程。分别于就诊时、咬伤后24 h、疗程结束时测定其血浆LPO、SOD、GSH-PX,比较两组患者三项指标的变化和临床疗效。结果两组患者在就诊时三项指标无明显差异(P>0.05);伤后24 h及疗程结束时,治疗组LPO明显低于对照组,SOD、GSH-PX显著高于对照组,治疗组疗效优于对照组(P<0.05)。结论蛇毒清胶囊能降低眼镜蛇咬伤患者血浆LPO水平,提高其SOD、GSH-PX活性,对眼镜蛇咬伤患者有清除氧自由基的作用。     

The variation of antioxidant defense system of Streptomyces sp. M4018 with respect to carbon sources

The effect of glycerol, glucose, and starch as carbon sources on the antioxidant defense system such as superoxide dismutase (SOD) and catalase (CAT) activities, pyruvate levels, and membrane lipid peroxidation (LPO) levels of Streptomyces sp. M4018, after isolation from the rhizosphere samples of Colutea arborescens and identification as a strain of S. hiroshimensis based on phenotypic and genotypic characteristics, were investigated. As an antioxidant defense enzyme, SOD activities increased up to 20 g/L of glycerol and 15 g/L of starch, while they showed negative correlation with glucose concentration. CAT activity variations of glycerol- and glucose-supplemented mediums showed significant positive correlations with the trend of SOD activities. However, CAT activity, in contrast to SOD, in Streptomyces sp. M4018 tended to decrease as the starch concentration increased. The production of pyruvate increased with respect to glycerol and starch up to 15 g/L, while it was positively correlated with glucose concentration. The highest pyruvate production was seen at 20 g/L glucose. Membrane LPO levels were negatively correlated with the activities of SOD and CAT enzymes, and the minimum LPO level was determined at 5 g/L of glucose, where SOD and CAT activities reached their maximum levels. Nevertheless, the higher SOD and CAT activities in a wider range of incubation period compared to the beginning by resulting in insignificant increases in membrane LPO levels showed the unusual antioxidant response capacities of the in Streptomyces sp. M4018 against the potentially deleterious effects of reactive oxygen species (ROS) for glycerol, glucose, and starch as carbon sources.     

微波对小白鼠超氧化物歧化酶和脂质过氧化物的影响

低剂量（９１５兆赫）的微波照射小白鼠后，用ＮＢＴ光化还原法测知脾脏的ＳＯＤ活性降低；聚丙烯酰胺凝胶电泳ＰＡＧＥ测知ＳＯＤ的电泳图谱发生了变化；脂质过氧化物增加。经恢复饲养，ＳＯＤ的活性持续下降，脂质过氧化物含量持续增高，但降低和增加的趋势于第１１天后趋于稳定，而ＳＯＤ的电泳酶谱却不能恢复到对照水平。本研究表明低剂量的微波照射对小白鼠的ＳＯＤ具有明显的损伤作用，并使有害于机体的脂质过氧化物增加。     

Lipid peroxidation in the kidneys of rats with nephritis induced by nephrotoxic serum and proteinuria induced by albumin overload]

Lipid peroxidation (LPO) stimulated by ascorbate was studied in renal cortex of 20 rats with nephrotoxic nephritis (NTN) and of 9 rats with proteinuria induced by a 3-day course of i. p. injections of the human serum albumin. At the early stages of NTN (0.5 h. and 3 h.) LPO activities were of the same values as in control rats. A small decrease in renal cortex LPO was found on the 4-th day of NTN when nephrotic syndrome has been developed. A significant reduction in LPO activity was observed on the 16-th day of NTN characterized by a more pronounced nephrotic syndrome. LPO activity in renal cortex of the rats with albumin overload proteinuria was also reduced. An inhibitory effect of proteinuria on LPO activity in kidney is discussed.     

Oxidative stress in zinc-induced dopaminergic neurodegeneration: implications of superoxide dismutase and heme oxygenase-1

The study was undertaken to investigate the effect of zinc (Zn) on glutathione S-transferase (GST) and superoxide dismutases (SOD) activities and on the expressions of cytosolic Cu, Zn-SOD (SOD1), mitochondrial Mn-SOD (SOD2), γ-glutamyl cysteine synthetase (γ-GCS) and heme oxygenase-1 (HO-1) in the nigrostriatal tissue of rats. Additionally, Zn-induced alterations in the neurobehavioral parameters, lipid peroxidation (LPO), striatal dopamine and its metabolites and tyrosine hydroxylase (TH) protein expression were measured to assess their correlations with the oxidative stress. Zn exposure reduced the locomotor activity, rotarod performance, striatal dopamine and its metabolites and TH protein expression. LPO, total SOD, SOD1 and SOD2 activities were increased while GST and catalase were reduced in a dose and time dependent manner. Expressions of SOD1 and HO-1 were increased while no change was observed in SOD2 and γ-GCS expressions. The results obtained suggest that Zn-induced augmentation of total SOD, SOD1, SOD2 and HO-1 was associated with increased oxidative stress and neurodegenerative indexes indicating the involvement of both cytosolic and mitochondrial machinery in Zn-induced oxidative stress leading to dopaminergic neurodegeneration.     

邻苯二甲酸二丁酯对翡翠贻贝抗氧化酶及脂质过氧化水平的影响

实验室条件下,研究了不同浓度邻苯二甲酸二丁酯(DBP)长期胁迫(15 d)对翡翠贻贝内脏团和外套膜抗氧化酶(超氧化物歧化酶SOD、过氧化氢酶CAT)及脂质过氧化(LPO)水平(以MDA含量表示)的影响,以及受胁迫翡翠贻贝在清洁海水中恢复阶段上述生化指标的变化特征.结果表明:胁迫阶段,0.5和2.5 mg.L-1DBP下翡翠贻贝内脏团SOD活性表现为先抑制后逐渐恢复,12.5和62.5 mg.L-1下则持续受到显著抑制;不同浓度组CAT活性均明显被抑制.LPO水平明显升高.外套膜中,2.5 mg.L-1下SOD活性受到持续诱导,其他浓度组则先被抑制,后随曝露时间延长逐渐被诱导;各浓度组CAT的变化波动较大,没有明显规律;而LPO水平明显升高.净化恢复阶段,12.5和62.5 mg.L-1DBP胁迫下的内脏团SOD和CAT活性恢复较慢,其LPO水平随时间延长逐渐恢复至对照组水平;外套膜中SOD活性呈持续升高趋势,CAT活性和LPO水平则随时间延长恢复到对照组水平.     

Oxidative stress in zinc-induced dopaminergic neurodegeneration: Implications of superoxide dismutase and heme oxygenase-1

Abstract

The study was undertaken to investigate the effect of zinc (Zn) on glutathione S-transferase (GST) and superoxide dismutases (SOD) activities and on the expressions of cytosolic Cu, Zn-SOD (SOD1), mitochondrial Mn-SOD (SOD2), γ-glutamyl cysteine synthetase (γ-GCS) and heme oxygenase-1 (HO-1) in the nigrostriatal tissue of rats. Additionally, Zn-induced alterations in the neurobehavioral parameters, lipid peroxidation (LPO), striatal dopamine and its metabolites and tyrosine hydroxylase (TH) protein expression were measured to assess their correlations with the oxidative stress. Zn exposure reduced the locomotor activity, rotarod performance, striatal dopamine and its metabolites and TH protein expression. LPO, total SOD, SOD1 and SOD2 activities were increased while GST and catalase were reduced in a dose and time dependent manner. Expressions of SOD1 and HO-1 were increased while no change was observed in SOD2 and γ-GCS expressions. The results obtained suggest that Zn-induced augmentation of total SOD, SOD1, SOD2 and HO-1 was associated with increased oxidative stress and neurodegenerative indexes indicating the involvement of both cytosolic and mitochondrial machinery in Zn-induced oxidative stress leading to dopaminergic neurodegeneration.     

Neuro-pathophysiologic effects during primary hyperactivation of the bed nucleus of the stria terminalis in the rat brain

Penicillin administration into the bed nucleus of stria terminalis (BNST) in the rat brain caused epileptiform activity (EpA)--the formation of the generator of pathologically enhanced excitation (GPEE) in the nucleus. GPEE was registered during the first 3 days. EpA was also detected in the amygdala during 5-8 days, and in the hippocamp during the whole period of registration (2-3 weeks). There was the generalized enhancement of synchronized EpA in the range of 6-10 oscillations per s., in some cases with high-amplitude spindle (7-8 oscillations per s.). 50% of animals had emotional behavioural disorders, a marked fear reaction was observed for a month and more. Some animals demonstrated psychotic-like paroxysms with the elements of stereotypy accompanied by high-frequency low-amplitude EpA. It is suggested that when a primary GPEE in BNST is formed, the structures of septo-hippocampal system (BNST, amygdala, hippocamp) play a role of pathological determinants under the influence of which the pathological system consisting of a number of limbic and extrapyramidal structures is formed. Its activity is clinically manifested in the complex polymorphic neuropathological syndrome.     

The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat heart and ameliorating role of vitamin E and vitamin C

Diazinon is one of the most widely used organophosphate insecticides (OPIs) in agriculture and public health programs. Reactive oxygen species (ROS) caused by OPIs may be involved in the toxicity of various pesticides. The aim of this study was to investigate how diazinon affects lipid peroxidation (LPO) and the antioxidant defense system in vivo and the possible ameliorating role of vitamins E and C. For this purpose, experiments were done to study the effects of DI on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in adult rat heart. Experimental groups were: (1) control group, (2) diazinon treated (DI) group, (3) DI+vitamins E and C-treated (DI+Vit) group. The levels of malondialdehyde (MDA) and the activities of SOD and CAT increased significantly in the DI group compared with the control group. The activity of SOD and the levels of MDA decreased significantly in the DI+Vit group compared with the DI group. The differences between the DI+Vit and control groups according to the MDA levels and the activities of both SOD and CAT were statistically significant. These results suggest that treating rats with a single dose of diazinon increases LPO and some antioxidant enzyme activities in the rat myocardium and, in addition, that single-dose treatment with a combination of vitamins E and C after the administration of diazinon can reduce LPO caused by diazinon, though this treatment was not sufficiently effective to reduce the values to those in control group.     

Accumulation and oxidative stress biomarkers in Japanese flounder larvae and juveniles under chronic cadmium exposure

This study investigated how Cd exposure affected oxidative biomarkers in Japanese flounder, Paralichthys olivaceus, at early life stages (ELS). Fish were exposed to waterborne Cd (0–48 µg L^− 1) from embryonic to juvenile stages for 80 days. Growth, Cd accumulation, activities of superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), glutathione S-transferase (GST, EC 2.5.1.18), and levels of glutathione (GSH) and lipid peroxidation (LPO) were investigated at three developmental stages. Flounder growth decreased and Cd accumulation increased with increasing Cd concentration. In metamorphosing larvae, CAT and SOD activities were inhibited and GSH level was elevated, while LPO was enhanced by increasing Cd concentrations. CAT and GST activities of settling larvae were inhibited but GSH level was elevated at high Cd concentrations. In juveniles, SOD activity and LPO level were increased but GST activity was inhibited as Cd concentration increased. Antioxidants in flounder at ELS were able to develop ductile responses to defend against oxidative stress, but LPO fatally occurred due to Cd exposure. These biochemical parameters could be used as effective oxidative biomarkers for evaluating Cd contamination and toxicity in marine environments: CAT, SOD, GSH, and LPO for metamorphosing stage; CAT, GSH, and GST for settling stage; and SOD, GST, and LPO for juvenile stage.     

Oxidative damage following cerebral ischemia depends on reperfusion - a biochemical study in rat

The extent of brain injury during reperfusion appears to depend on the experimental pattern of ischemia/reperfusion. The goals of this study were: first, to identify the rate of free radicals generation and the antioxidant activity during ischemia and reperfusion by means of biochemical measurement of lipid peroxidation (LPO) and both enzymatic (superoxid dismutase - SOD, catalase - CAT, glutathion peroxidase - GPx) and non-enzymatic antioxidants activity (glutathione - GSH); and second, to try to find out how the pattern of reperfusion may influence the balance between free radical production and clearance. Wistar male rats were subject of four-vessel occlusion model (Pulsinelly & Brierley) cerebral blood flow being controlled by means of two atraumatic arterial microclamps placed on carotid arteries. The level of free radicals and the antioxidant activity were measured in ischemic rat brain tissue homogenate using spectrophotometrical techniques. All groups subjected to ischemia shown an increase of LPO and a reduction of the activity of enzymatic antioxidative systems (CAT, GPx, SOD) and non-enzymatic systems (GSH). For both groups subjected to ischemia and reperfusion, results shown an important increase of LPO but less significant than the levels found in the group with ischemia only. Statistically relevant differences (p<0.01) between continuous reperfusion and fragmented reperfusion were observed concerning the LPO, CAT, SOD and GSH levels, oxidative aggresion during fragmented reperfusion being more important.     

THE VARIATION OF ANTIOXIDANT DEFENSE SYSTEM OF Streptomyces sp. M4018 WITH RESPECT TO CARBON SOURCES

The effect of glycerol, glucose, and starch as carbon sources on the antioxidant defense system such as superoxide dismutase (SOD) and catalase (CAT) activities, pyruvate levels, and membrane lipid peroxidation (LPO) levels of Streptomyces sp. M4018, after isolation from the rhizosphere samples of Colutea arborescens and identification as a strain of S. hiroshimensis based on phenotypic and genotypic characteristics, were investigated. As an antioxidant defense enzyme, SOD activities increased up to 20 g/L of glycerol and 15 g/L of starch, while they showed negative correlation with glucose concentration. CAT activity variations of glycerol- and glucose-supplemented mediums showed significant positive correlations with the trend of SOD activities. However, CAT activity, in contrast to SOD, in Streptomyces sp. M4018 tended to decrease as the starch concentration increased. The production of pyruvate increased with respect to glycerol and starch up to 15 g/L, while it was positively correlated with glucose concentration. The highest pyruvate production was seen at 20 g/L glucose. Membrane LPO levels were negatively correlated with the activities of SOD and CAT enzymes, and the minimum LPO level was determined at 5 g/L of glucose, where SOD and CAT activities reached their maximum levels. Nevertheless, the higher SOD and CAT activities in a wider range of incubation period compared to the beginning by resulting in insignificant increases in membrane LPO levels showed the unusual antioxidant response capacities of the in Streptomyces sp. M4018 against the potentially deleterious effects of reactive oxygen species (ROS) for glycerol, glucose, and starch as carbon sources.     

Effect of conditioned-reflex bilateral avoidance learning on lipid components of the rat brain

The active avoidance training of rats resulted in a depletion of lipid peroxidation (LPO) products in cerebral cortex. LPO inhibition was also shown in cerebral cortex of "active control" group receiving +non-combined stimuli (the effect of short-term stress). LPO inhibition was more pronounced in rats staining a training criterion compared to rats which received combined stimuli but did not reach the criterion. In the active control group LPO inhibition was accompanied by total phospholipids accumulation and cholesterol depletion in cortical lipid extracts. Irrespective of attaining the criterion in all rats trained for active avoidance the accumulation of cholesterol was seen. Active avoidance training affected also the phospholipid composition of cerebral cortex.