Malondialdehide Research Articles

Nasal Administration of Quercetin Liposomes Modulate Cognitive Impairment and Inhibit Acetylcholinesterase Activity in Hippocampus

Problem statement: Oxidative stress is a major factor implicated in t he degeneration of cholinergic neurons in Alzheimer's Disease (AD). Several reports have indicated that antioxidant intake is beneficial to delay or inhibit the progre ssion of this disease. Presently, Acetylcholinester ase (AChE) inhibitors are the mainstay of therapy for A D. Quercetin, one of the flavonoids in fruits and vegetables, has a powerful antioxidant activity bot h in vitro and in vivo . However, the potential of quercetin as Acetylcholinesterase (AChE) inhibitors , an important aspect for neuroprotection, has not been properly investigated. Approach: This study was designed to evaluate the anti-choli nesterase activity and improves cognitive function of quercet in liposomes via nasal administration in a rat AF64A injection model of AD. Male Wistar rats were pretreated with quercetin liposomes, containing 0.5 mg of quercetin in 20 �L via intranasal route once daily continually for 3 weeks. Learning and memory was evaluated using the Morris water maze test at 7 days after the lesioning and then the rats were sacrificed for determining the contents of Ace tylcholinesterase (AChE), the activities of Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Malondialdehide (MDA), a lipid peroxidation product in the hippocampus. Results: AF64A with nasal administration of free liposomes showed the loss of cognitive performance in Morris water maze test, increase in the markers of oxidative damage (MDA, SOD and GPX) and the AChE activity in the hippocampus. However, AF64A with nasal administration of quercetin liposo mes reversed all the parameters significantly. Conclusion: Our studies demonstrated that quercetin liposomes via nasal administration may have a therapeutic importance in the clinical management o f Alzheimer's disease.

Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit

In this study, it was aimed to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on cisplatin hepatotoxicity. Thirty New Zealand rabbits were divided into 5 groups as group 1 (saline-injected control, C), group 2 (1% ethanol; vehicle for CAPE, E), group 3 (CAPE), group 4 (cisplatin, CS) and group 5 (cisplatin plus CAPE, CS+CAPE). Cisplatin caused increased immunoreactivity against inducible nitric oxide synthase (iNOS), but CAPE treatment reduced the immunoreactive hepatocytes. Liver malondialdehide (MDA), nitric oxide (NO ·) levels and xanthine oxidase (XO) activities were higher in CS than in groups C and E. Cisplatin treatment also significantly decreased the tissue reduced glutathione (GSH) concentration compared to groups C and E. CAPE administration normalized the tissue GSH level and XO activity in group CS+CAPE, whereas CAPE treatment did not affect MDA level in group CS+CAPE. In addition, CAPE treatment significantly depressed the cisplatin-induced NO · increase in group CS+CAPE. Histopathologically, cisplatin caused hydropic degenerations, necrosis in hepatocytes, sinusoidal congestion, Kupffer cell proliferation and mononuclear cell infiltration. These alterations were less severe in rabbits receiving CS+CAPE. Parallel to histopathology, cisplatin increased serum AST and ALT levels, whereas CAPE treatment significantly reduced cisplatin-induced AST and ALT rise in the serum. Results suggest that cisplatin causes oxidative and nitrosative damage to hepatocytes. Cisplatin-induced increase in XO and NO · could contribute oxidative stress in the hepatotoxicity. CAPE shows partial protection against cisplatin-associated biochemical and histopathological alterations.

THE EFFECT OF VACCINIUM MYRTILLUS AND VACCINUM VITIS-IDAEA FRUITS EXTRACTS ON THE ANTIOXIDANT SYSTEM OF MAMALIAN ORGANISMS

SUMMARY The present paper deals with the study of some Vaccinium myrtillus and Vaccinum vitis-idaea fruits extracts effects on the antioxidant system of guinea pigs. Both extracts stimulated the antioxidant system of the cells: it doesnt not effect the normal function of the liver and stimulates the absorption of calcium and phosphorus. Especially; Vaccinum myrtil us stimulates the haemoglobine synthesis and also the iron absorption. It is a much more antioxidant as Vaccinum vitis-idaea as there were registered lower levels of malondial dehide (MDA) respectively higher concentration of reduced glutathione (GSH) in comparison with the Vaccinum vitis-idaea . In the same time lower activities of superoxid di smutase (SOD); glutathione peroxidase (G-px) and glutathione reduc tase (G-red) were registered in the treatment with Vaccinum myrtilus extract. Free radicals; respectively reactive species of t he oxigen (ROS) in physiological concentration are stimulating the development and t he cell division. A mutation at cell level can be the cause of permanent deviation of the oxid ative reactions with RSO development in excess. In very large doses; ROS lead to apoptosis. As there are quite few studies in this field; in the present work we study the antioxidant proper ties of some Vaccinium myrtillus and Vaccinum vitis-idaea fruits extracts on the antioxidant system of guine a pigs; as a possible oxidative stress barrier as both of the extracts co ntain antioxidant components as flavonoides; antocianines; etc. The experiment was carried on 36 adult female guinea pigs (divided in three groups) and maintained in good physiological conditions. Th ey were divided in three groups. Each group included 12 guinea pigs.L1- control; received tap water ad libitum during 14 days; L2 - received during 14 days 0.5 ml i.m. of the Vaccinium myrtillus extrac t; L3- received during 14 days 0.5 ml i.m. of the Vaccinium vitis-idaea extract After 14 days blood (on heparine); by cardiac punction and tissue samples were collect ed under general narcosis from L1; L2 and L3. The data are presented as means ± S.D. values. ANOVA; TTest were used. The best antioxidant properties has the Vaccinium myrtillus extract as it maintained a normal function of the liver (GPT; GOT and GGT were situated in normal values) and stimulates the absorption of calcium and phosphorus ; the haemoglobine synthesis and also the

Erdosteine and Ebselen As Useful Agents in Intestinal Ischemia/Reperfusion Injury

Reactive oxygen and nitrogen species generated during reperfusion of the tissue are characteristic of ischemia/reperfusion (I/R) injury. The purpose of the present study was to investigate whether erdosteine and ebselen, molecules with antioxidant properties and peroxynitrite scavenging capability, respectively, can reduce oxidative stress and histological damage in the rat small bowel subjected to mesenteric I/R injury. Forty Sprague-Dawley rats were divided into five groups equally: sham, I/R, I/R plus erdosteine, I/R plus ebselen, and I/R plus erdosteine and ebselen. Intestinal ischemia for 45 min and reperfusion for 3 d were carried out. Ileal specimens were obtained to determine the tissue levels of malondialdehide (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), glutathione peroxidase (GPx), nitrite/nitrate (NO(x)) level and histological changes. Intestinal I/R resulted in increased tissue MDA, PCC, and NO(x) levels and decreased SOD and GPx activities. Both erdosteine and ebselen alone significantly decreased MDA, PCC, and NO(x) levels and increased antioxidant enzymes activities, but all values were different from control. These changes almost returned to control values in the group treated with erdostein and ebselen. Histopathologically, the intestinal injury in rats treated with erdosteine and ebselen as well as combination were less than I/R group. Both erdosteine and ebselen were able to attenuate I/R injury of the intestine via inhibition of lipid peroxidation and protein oxidation, maintenance of antioxidant, and free radical scavenger properties. Nevertheless, combination treatment showed more promising results, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing intestinal I/R injury.

Preventive effect of α‐lipoic acid and ebselen on rat intestine against ischemia/reperfusion injury

Purpose: Reactive oxygen species (ROS) and reactive nitrogen species(RNS) generated during reperfusion of the tissue are characteristic of ischemia and reperfusion (I/R) injury. The present study was designed to evaluate whether a‐Lipoic Acid (a‐LA) and Ebselen have protective effect in intestinal I/R injury.Methods: Fourty Sprague‐Dawley rats were divided into five groups equally: Group‐1 Sham‐operated; Group‐2 I/R; Group‐3 I/R+a‐LA; Group‐4 I/R+Ebselen; Group‐5 I/R+a‐LA+Ebselen. Intestinal ischemia for 45 min and reperfusion for 3 days were carried out. Ileal specimens were obtained to determine the tissue levels of Malondialdehide (MDA), Protein Carbonyl (PC) content, Superoxide dismutase (SOD) and Glutation Peroxidase (GPx) and histologic changes.Results: There was a statistically significant decrease in SOD and GPx levels, with an increase in MDA and PC content and intestinal mucosal injury in intestinal I/R group (p<0.05). a‐LA and Ebselen led to a significantly increase in SOD and GPx level, with a decrease in MDA and PC content and intestinal injury when compared with I/R group, (p<0.05). Although shortness of villous and epithelial lifting was seen in the rats subject to I/R, there was slightly injury in mucosa in treatment groups.Conclusion: a‐LA and Ebselen played significant protective role in attenuating I/R injury of the intestine by scavenging ROS and RNS.

Determination of some heavy metal levels and oxidative status in Carassius carassius L., 1758 from Eber Lake

In this study, the levels of some heavy metals (Al, Cd, Co, Cr, Cu, Fe, Li, Mn, Ni, Pb and Zn) in muscle, gill, and liver of Carassius carassius and in the water samples from Eber Lake (Afyonkarahisar, Turkey) have been investigated. Additionally, one of the lipid peroxidation markers, malondialdehide (MDA) and glutathion (GSH) levels were investigated. All the metal analysis was performed by using ICP-AES. According to results obtained, it was observed that heavy metals were accummulated in liver in the highest degree and lowest one in the muscle tissues. MDA and GSH levels varied in the seasons but their winter levels were found to be statistically meaningful when compared with other seasons. The obtained data of metals from the study were compared with the acceptable levels of Turkish governmental regulation and they were found not to be harmful for human health. On the other hand, it was suggested that oxidative stress markers should be checked regularly in order to get important data for continuous life of aquatic organisms.

Ergothioneine Modulates Proinflammatory Cytokines and Heat Shock Protein 70 in Mesenteric Ischemia and Reperfusion Injury

Ergothioneine (EGT) is a natural compound that is synthesized by soil bacteria in fungal substrates and exhibits antioxidant functions in many cell models. The purpose of this study was to investigate the effect of EGT on mesenteric ischemia and reperfusion injury. Rats were supplemented with or without l-ergothioneine (10 mg/kg/d) for 15 days prior to intestinal ischemia. Animals were subjected to ischemia induced by clamping the superior mesenteric artery for 60 min followed by reperfusion. Serum tumor necrosis factor (TNF)-alpha and interleukin-1beta (IL-1beta) levels, tissue malondialdehide (MDA), myleoperoxidase (MPO), and heat shock protein (HSP) 70 levels, as well as histological findings, were evaluated after 1, 2, and 4 h of reperfusion. Serum TNF-alpha and IL-1beta levels, and tissue MDA and MPO activities at 1, 2 and 4 h after reperfusion in the EGT group, were significantly lower than the control group (P < 0.05). Tissue HSP-70 levels of the study group were significantly greater than the control group at any time point of reperfusion. No significant differences in tissue damage including morphological changes ranging from villous denudation to focal necrosis, ulceration, hemorrhage, and architectural disintegration at 1 and 2 h after reperfusion exist between the two groups; however, after 4 h of reperfusion, the tissue damage based on histopathologic scores by Chiu was considerably lower in the study group (P < 0.05). After 4 h of reperfusion, focal epithelial lifting and occasional areas of denuded villi could be seen in the samples of the treated animals, thus preserving villous height and mucosal architecture. EGT attenuates mesenteric ischemia reperfusion injury in rat intestine by increasing tissue HSP-70 and decreasing TNF-alpha, IL-1beta, MDA, and MPO levels. EGT also improves morphological alterations, which occurred after IR injury after prolonged periods of reperfusion.

Melatonin attenuates radiation-induced learning deficit and brain oxidative stress in mice

Oxidative stress has been implicated in cognitive impairment in both experimental animals and humans. This implication has led to the notion that antioxidant defence mechanisms in the brain are not sufficient to prevent oxidative damage, and that dietary intake of a variety of antioxidants might be beneficial for preserving brain function. The present study, therefore, aimed to investigate the protective effect of melatonin against radiation-induced impairment in the learning ability of mice. Twenty days oral administration of melatonin (0.1 mg/kg b.w.), followed by an acute exposure to ¡-radiation (6 Gy), inhibited the radiation-induced decline in learning ability. Biochemical estimation of brain protein carbonyls, malondialdehide (MDA) and reduced glutathione (GSH) in these mice indicated that radiation-induced augmentation of protein oxidation and lipid peroxidation had been significantly ameliorated in melatonin treated, irradiated mice. Radiation-induced deficit of glutathione was also normalized by melatonin administration, as there was no statistical difference from normal at P

The intervention of antioxidant therapy on platelet adhesion and immunomodulation in experimental physical stress

During effort overstress the reactive oxygen species act chiefly on unsaturated lipids, inducing the formation of certain peroxidation products. We have investigated malondialdehide (MDA), platelet adhesion index, and immunological activation parameters during effort overstress and administration of vitamins E and C. Biochemical measurements were performed on erythrocytes and heart homogenate. In the vitamin E supplemented group, the platelet adhesion index was constantly correlated with the MDA level (p < 0.001). There is a protecting effect concerning the oxidative stress in animals pretreated with vitamin E and C, which is expressed through the diminution of the MDA quantity both in the erythrocyte and in the heart. The physical effort required by swimming led to a decrease in the NBT test values and in the activity of the serum complement. The steady administration of vitamin E in the effort overstress, due to its antioxidant properties, causes the progressive decrease in peroxidation and platelet adhesion.

Oxidative stress is closely related to clinical severity of pre-eclampsia

Pre-eclampsia is a hypertensive disorder of pregnancy in which enzymatic antioxidant defenses fail and tissues are injured. This prospective case-control study evaluated whether pre-eclamptic women and their newborns show higher degrees of oxidative stress than normal pregnancies and sought to determine if this stress is related to clinical severity. Forty-four pre-eclamptic and thirty healthy pregnant women attending two hospitals in Valparaíso, Chile, were studied. The following plasmatic variables of antioxidant capacity were evaluated: glutathione peroxidase activity (GPx), total antioxidant capacity measured by oxidation of ABTS substrate (2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), and superoxide dismutase activity (SOD). malondialdehide (MDA) was measured to evaluate lipoperoxidation. The evaluation was performed at diagnosis of pre-eclampsia, delivery, 30 days and 120 days post delivery. Newborns were studied at delivery through umbilical cord blood samples. Our analysis shows that antioxidant enzyme activity (SOD, GPx, ABTS) was significantly decreased, while lipoperoxidation (MDA) was increased in both pre-eclamptic groups compared to normal pregnant women (p<0.01). Statistically significant difference was found between mild and severe pre-eclamptic groups (p<0.01), for all biochemical markers studied. Therefore, the clinical severity of this pathology is closely related to the degree of oxidative stress.

Serum Malondialdehyde Levels and Superoxide Dismutase Activities in Pulmonary Tuberculosis and Lung Cancers

Methodology: The present investigation has been undertaken to study the levels of lipid peroxide (LP) and antioxidant enzyme superoxide dismutase (SOD) activities in sera of lung cancers (Lc) and tb. Forty-two patients and fourteen healthy cases were enrolled into the study. Group I had seventeen subjects with Lc, group II had twenty-five patients with tb and group III had fourteen healthy cases. The malondialdehide (MDA) and superoxide dismutase (SOD) activities in sera were quantified.

Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach.

Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative response of the organism to stimulate gluconeogenesis. They showed for the first time that HCB causes impairment of the gluconeogenic pathway. Therefore, the reduced levels of glucose would thus be the consequence of decreased gluconeogenesis, enhanced glucose storage, and unaffected glycolysis. The impairment of gluconeogenesis (especially for PEPCK) and the related variation in glucose levels caused by HCB treatment could be a consequence of the oxidative stress produced by the fungicide. Tryptophan adds its effect to this decrease in the higher phases of HCB intoxication, where its levels overcome the control values possibly owing to the drastic decline of URO-D. This derangement of carbohydrates leads porphyric hepatocytes to have lower levels of free glucose. These results contribute to our understanding of the protective and modulatory effect that diets rich in carbohydrates have in hepatic porphyria disease.

Effects of leukocyte-depleted warm blood cardioplegia on cardiac and endothelial function.

It has been reported that neutrophils and platelets have deleterious effects on myocardium and endothelium during and after ischemia. In this study we evaluated the effects of a leukocyte-depleting filter (Sepacell PLX, Asahi medical, Tokyo) during warm blood cardioplegia and early reperfusion on cardiac and endothelial function in the blood-perfused rat heart. Hearts (n = 7 per group) from donor rats were excised and perfused with blood at 37 degrees C from a support rat. After 10 min of stabilization, the hearts were arrested for 60 min with warm blood cardioplegia given at 20 min intervals. This was followed by 60 min of reperfusion. A leukocyte-depleting filter was used during the cardioplegia and the initial 10 min of reperfusion in the experimental group (Group F) and it was not used in the control group (Group N). Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximum rate of left ventricular pressure rise (+dp/dt) and maximum rate of left ventricular pressure fall (-dp/dt) were measured as indices of left ventricular function before and after cardioplegic arrest. Coronary sinus effluent was obtained and the levels of MB isozyme of creatine kinase (CKMB), malondialdehide (MDA), elastase and thromboxane B2 (TXB2) were measured as indices of myocardial and endothelial injury. After 60 min of reperfusion, acetylcholine (Ach.) was administered to the coronary perfusate and the difference of nitric oxide (NO) concentration between inflow and outflow, and coronary blood flow were measured as an indication of endothelial function. Group F showed significantly lower LVEDP than Group N at 10 min of reperfusion. The elastase levels were significantly (p < 0.05) lower and the CKMB levels tended (p < 0.1) to be lower in Group F at 60 min of reperfusion. The administration of Ach. to the coronary perfusate showed significantly (p < 0.05) greater coronary blood flow and NO production in Group F. The results suggested that the use of a leukocyte-depleting filter during warm blood cardioplegia and early reperfusion preserves endothelial function and left ventricular diastolic compliance. The technique may provide beneficial effects by reducing reperfusion injury in patients undergoing cardiac surgery.

The induction of lipid peroxidation by E. coli lipopolysaccharide on rat hepatocytes as an important factor in the etiology of endotoxic liver damage

Oxygen-derived radicals have been suggested to produce tissue injury during endotoxic shock by initiating lipid peroxidation. In order to investigate the induction of lipid peroxidation by Escherichia coli 0111:B4 lipopolysaccharide (LPS) on hepatocytes, malondialdehide (MDA) and superoxide dismutase (SOD) activity have been evaluated in vivo and in vitro using two experimental models: rat liver after the establishment of endotoxic reversible shock, and cultured hepatocytes after treatment with LPS. Liver MDA levels were increase in vivo during the acute-phase of endotoxic shock, decreasing below control values in the recovery phase. An inverse pattern was obtained when SOD activitiy was measured, consistent with an active system of cellular protection. Similar results were obtained in vitro after treatment of cultured hepatocytes with LPS (50 μg/ml), thus indicating that a direct LPS cytotoxic effect on hepatocytes exits during the endotoxic process. The direct LPS interaction induced alterations in Ca 2+ permeability of hepatocyte plasma membrane as detected by flow cytometry using the fluorescent probe Indo-1.

Clinical effects of six-month short time biofiltration

The clinical effects of six-month short time biofiltration (SBF) were evaluated using a B-A-B' study (B, B': conventional bicarbonate hemodialysis; CBHD, A:SBF) in ten patients maintained on CBHD three times a week. An F80 hemodiafilter (1.9 m2, polysulfone, Fresenius) was used. In addition to routine clinical parameters for a patient on regular dialysis treatment, plasma von Willebrand factor antigen (vWF) (an index of stimulation of vascular endothelium), and the methylguanidine/creatinine ratio (MG/Cr) and malondialdehide (MDA) (indices of the levels of oxygen radicals), were evaluated. Nine patients completed the study, one patient dropping out at the 12th week of A because of muscle cramps during SBF. The treatment time was 2 hours in six cases and 2.5 hours in three cases. The mean blood flow rate was 280 +/- 42 (SD) minutes. Using the urea kinetics model, the mean KT/V was 1.26 +/- 0.28, and the mean protein catabolic rate was 1.22 +/- 0.18 g/kg body weight/day at the end of A. No change in ultrafiltration, blood pressure, cardiac function (assessed by echocardiography), CTR, human atrial natriuretic peptide, total protein, albumin, uric acid, serum creatinine, sodium, calcium, inorganic phosphorus, vWF, or MDA was found between each period. Blood urea nitrogen, c-PTH, and MG/Cr increased during the A period. Serum magnesium and beta-2 microglobulin decreased during the A period. Blood gas results, on the whole, did not change. In a patients, however, acidosis gradually developed. An increase in substitution fluid from 5 L/session to 7.5 L/session improved the acid-base balance in that patient. In conclusion, SBF is as effective as CBHD in removing small molecules and maintaining cardiocirculatory status, and is superior to CBHD in removing beta 2-microglobulin and is less stimulative to the endothelium than CBHD.