Malonyldialdehyde Levels Research Articles

Lipid peroxidation and impaired vascular function in patients with type 1 diabetes mellitus

Patients with type 1 diabetes mellitus (T1DM) develop microvascular complications during the course of the disease. Oxidative stress is the main mechanism of the microvascular damage. Currently no specific and reliable laboratory tests are available for screening of early microvascular changes. 56 patients with T1DM were included. We measured their serum levels of malonyl dialdehyde and reactive aldehydes with chain lengths C6–C12, which are known to be generated during lipid peroxidation, a process associated with oxidative stress. Serum levels of aldehydes were compared with the parameters of microvascular reactivity (MVR) examined by laser Doppler flowmetry and with the parameters of blood glucose control (glycated hemoglobin, glycemic variability using continuous glucose monitoring). In this cross-sectional observational study, higher levels of reactive aldehydes were associated with impaired skin MVR in T1DM. However, the parameters of glucose control were not associated with lipid peroxidation or MVR in our study. Therefore, we suggest that other than simple glycemic mechanism may be more important in the process of reactive aldehyde generation in T1DM.

Effect of Iloprost, a Prostacyclin Analogue, on Myocardial Ischemia-Reperfusion Injury

Myocardial ischemia-reperfusion injury continues to be observed during open heart surgery. Various experimental models have been developed to overcome this injury and to increase postoperative prognosis. This study was conducted to assess the effect that iloprost, a prostacyclin analogue, can have on myocardial ischemia-reperfusion injury. We evaluated tissue damage by measuring the levels of malonyldialdehyde (MDA), glutathione, and nitric oxide (NO) in tissue and perfusates. In this study, 20 guinea pig hearts were prepared by using the modified Langendorff perfusion apparatus to form control (n = 10) and experimental study groups (n = 10). Following a preischemic period of perfusion and an ischemic period of 20 minutes, control hearts were perfused with Krebs–Henseleit solution. In the experimental group, iloprost (0.45 μg/kg per hour) was included in the perfusates for the last 10 minutes of the preischemic phase. Following cardiac stabilization, heart rate (pulse/min), contractility (mm), and aortic pressure (mmHg) values were recorded at the end of preischemia, postischemia, and reperfusion. Perfusate and tissue analyses for glutathione, MDA, and NO levels were made in each group at the end of experiments. Iloprost was found to have protective effects against myocardial ischemia by means of increased myocardial contractility, decreased tissue/perfusate glutathione levels and inhibited rise of tissue/perfusate MDA observed in the iloprost-treated experimental group. Future investigations on myocardial ischemia-reperfusion injury must evaluate iloprost-related mechanisms.

Beneficios de la suplementación con zinc sobre el estado metabólico, redox y de elementos traza en un modelo de diabetes moderada en ratas

Context: The function of zinc in the diabetes prevention, its management and complications are not clear. Aim: To determine the effect of zinc supplementation on the metabolic, redox and trace element status in mild diabetic Wistar rats. Methods: Thirty-two female Wistar rats equally distributed in four groups were studied: C: Control, CZn: Control-Zn-supplemented, D: Diabetic, DZn: Diabetic-Zn-supplemented. Diabetes was induced by streptozotocin (STZ-100 mg/kg-sc, second postnatal day). In adulthood, the corresponding groups were supplemented with zinc sulfate (ZnSO4x7H2O-100 mg/kg) for 14 days. Results: Zn supplementation in diabetic rats: -alleviated diabetes markers such as HbA1C, HOMA cell-β index, tolerance to glucose and insulin, polydipsia and polyuria; -decreased the Cu/Zn ratio levels in serum and tissues; -in liver and kidney improved excessive accumulation of Cu and increased the Zn concentrations, without causing toxicity; -increased the reduced glutathione (GSH) levels in liver and kidney and decreased the malonyldialdehyde (MDA) levels in liver, without changes in advanced oxidation protein products (AOPP); -evidenced negative correlation between tissue levels of Zn Vs MDA and AOPP. Conclusions: Zn supplementation favored glycemic control in rats with moderate diabetes, contributing to recovery of the metabolic, redox and trace elements status. Regulation of diabetes complications was associated with the antioxidant action of Zn. Nutritional supplementation with zinc may be suggested to prevent complications of diabetes in conditions of deficiency of this micronutrient.

Genetic polymorphism and antioxidant activity in interventions of tobacco-related diseases of the abdominal aorta.

IntroductionThe aim of this study was to determine the genetic polymorphisms of some antioxidant enzymes together with oxidative stress and the response of some antioxidant enzymes against this situation in vascular and endovascular interventions performed for diseases of the infrarenal abdominal aorta.Material and methodsTwenty-four current or ex-smoker patients (eight aortoiliac occlusive disease (AOD), 16 abdominal aortic aneurysm (AAA)) who were operated were included in this pilot study. Malonyl dialdehyde (MDA) levels, as an indicator of oxidative stress, reduced glutathione, catalase and superoxide dismutase enzymes, which are indicators of antioxidant status, which were measured in aortofemoral bypass in AODs, and in endovascular abdominal aortic aneurysms repairs in the preoperative, operative, and postoperative periods. Genetic polymorphisms of these antioxidant enzymes developing a response to the damage in the preoperative blood samples were determined by using the PCR-RFLP method.ResultsThe lack of a significant increase of MDA (nmol/ml preoperative: 2.57 ±0.19, operative: 2.59 ±0.21, postoperative: 2.64 ±0.22, p = 0.63) in the oxidative damage in the operative and postoperative periods compared to the preoperative period prevented the damage and was thought to be associated with the elevation of some effective antioxidant parameters in the operative and postoperative periods.ConclusionsIt may be thought that both types of interventions are quite reliable in terms of oxidative damage and, accordingly, the effect of the procedure-associated oxidative damage in the postoperative complications is low or ineffective. Two genotypes were obtained in each of the three gene areas of the patients, and no statistical significance was determined between the genotypes (p > 0.05).

Identification of therapeutic effect of glucagon-like peptide 1 in the treatment of STZ-induced diabetes mellitus in rats by restoring the balance of intestinal flora.

The objective of this study was to identify the therapeutic effect and the underlying mechanism of glucagon-like peptide 1 (GLP-1) in the treatment of STZ-induced diabetes mellitus (DM). Mice were treated with STZ to establish an animal model of DM, which was further treated with a GLP-1 receptor agonist. Subsequently, the status of glucose, insulin, nitric oxide, inflammatory and oxidative factors was evaluated and compared among Sham, STZ, and STZ + GLP-1 groups. In addition, the intestinal flora spectrum in each group was also evaluated. In this study, it was found that the administration of STZ increased the level of glucose and glycosylated hemoglobin but reduced the level of insulin. It was also found that the levels of inflammation and oxidative stress in STZ-induced DM were both enhanced, as evidenced by a decreased level of catalase, superoxide dismutase, glutathione peroxidase, as well as increased levels of malonyldialdehyde, interleukin-1β (IL-1β), and IL-6. Meanwhile, the expression of nitric oxide, a factor associated with both oxidative stress and inflammation, was also suppressed in STZ-induced DM. More importantly, the imbalance of intestinal flora was observed in STZ-induced DM, as shown by a decreased level of both total bacteria and that of some strains including Clostridium, Bacteroides, Lactobacilli, and Bifidobacteria. In summary, the findings of this study confirmed the antihyperglycemic effect of GLP-1 and demonstrated that the therapeutic effect of GLP-1 in the treatment of STZ-induced DM was mediated, at least partially, by its ability to restore the balance of intestinal flora.

The protective effects of a novel synthetic β-elemene derivative on human umbilical vein endothelial cells against oxidative stress-induced injury: Involvement of antioxidation and PI3k/Akt/eNOS/NO signaling pathways

Antioxidant therapy is considered as promising strategy for treating oxidative stress-induced cardiovascular disease. Bis (β-elemene-13-yl) glutarate (BEG) is a novel β-elemene derivative. Herein, we examined the antioxidant activity of BEG on human umbilical vein endothelial cells (HUVECs) after injury with hydrogen peroxide (H2O2) and investigated the mechanism involved. HUVECs were divided into the following groups: control group (untreated cells); treated groups (cells treated with 0.1, 1, 10 μmol/L of BEG); positive control group (cells treated with 0.1 mM Vitamin E); model group (cells treated with 0.5 mM H2O2 alone). Cells were pre-incubated with or without BEG for 24 h and then incubated for a further 2 h with 0.5 mM H2O2. Our results showed that BEG significantly reduced H2O2 induced loss in endothelial cell viability, reactive oxygen species (ROS) production, reduced lactate dehydrogenase (LDH) release, and malonyldialdehyde (MDA) level in a concentration-dependent manner. Also, BEG increased the cellular the superoxide dismutase (SOD) activity. Moreover, we found that H2O2 decreased Akt and eNOS phosphorylation, which perhaps, indirectly reduced nitric oxide (NO) production. These effects induced by H2O2, however, were reduced by pre-treatment with BEG. BEG effects were inhibited by a PI3K inhibitor (wortmannin) and eNOS inhibitor (L-NAME). In conclusion, the present study demonstrated that BEG has antioxidant activity. Furthermore, BEG reduced H2O2-induced endothelial cells injury by the involvement of antioxidation and PI3K/Akt/eNOS/NO signaling pathways.

LncRNA MALAT1 promotes the apoptosis and oxidative stress of human lens epithelial cells via p38MAPK pathway in diabetic cataract

BackgroundLncRNAs are involved in various biological processes and disorders. We aimed to investigate the role of lncRNA MALAT1 deregulation in the pathogenic mechanism of diabetic cataract (DC). MethodsThe expression of MALAT1 in the tissues and cells was detected by qRT-PCR. The levels of SP1, p38 and apoptosis-related protein were assessed by Western blot assay. Chromatin immunoprecipitation assay and Dual luciferase assay were performed to evaluate the relationship between SP1 and MALAT1. The viability and apoptosis of human lens epithelial cells (HLECs) were analyzed by MTT assay and flow cytometry. The levels of malonyldialdehyde (MDA), superoxide dismutase (SOD) and phospholipid hydroperoxide glutathione peroxidase (GSH-Px) were used to examine the level of oxidative stress. ResultsMALAT1 not only was aberrantly expressed in DC anterior lens capsule tissues and high glucose (HG)-treated HLECs, but also were up-regulated by HG to promote the apoptosis and oxidative stress of HLECs. HG induced the up-regulation of MALAT1 via SP1 binding MALAT1 promoter regions in HLECs. Moreover, p38 was up-regulated in HG-treated HLECs, and knockdown of p38 reversed the effect of MALAT1 over-expression on HLECs. ConclusionHG induced the up-regulation of MALAT1 in HLECs via SP1 binding SP1 binding MALAT1, which promoted the apoptosis and oxidative stress of HLECs through the activation of p38MAPK signaling pathway.

Effects of iron supplementation and nutrition education on haemoglobin, ferritin and oxidative stress in iron-deficient female adolescents in Palestine: randomized control trial.

Iron deficiency and iron-deficiency anaemia are associated with oxidative stress, but their role is largely unclear. Information is scarce on the effects of iron supplementation on biomarkers of oxidative stress in humans. This study evaluated the effectiveness of iron supplementation and nutrition education on improving the levels of haemoglobin and ferritin, and decreasing oxidative stress among iron-deficient female adolescents in Gaza, Palestine. A total 131 iron-deficient female adolescents were recruited and allocated randomly into 3 different groups. The iron supplementation group (A) received 200 mg of ferrous fumarate weekly during the 3-month intervention, the iron supplementation with nutrition education group (B) received iron supplements with nutrition education sessions, and the control group (C) did not receive any intervention. The levels of haemoglobin, ferritin and malonyl dialdehyde were measured at baseline, after 3 months (at which point the intervention was stopped), and then 3 months later. Trial registration number: ACTRN12618000960257. Haemoglobin levels increased significantly after supplementation in both groups A and B. At the follow-up stage (3 months after stopping the intervention), iron and haemoglobin levels in group B continued to increase and malonyl dialdehyde decreased. In Group A, haemoglobin, ferritin and malonyl dialdehyde levels decreased after 3 months of stopping the intervention. No changes were seen in Group C. A nutrition programme should be adopted and integrated into comprehensive intervention programmes to target iron-deficiency anaemia among female adolescents in Palestine.

Effect of cadmium on anion exchange capability through Band 3 protein in human erythrocytes

The efficiency of Band 3 protein, mediating HCO3-/Cl- exchange across erythrocytes membrane, is reduced by oxidative stress. The aim of the present study was to verify whether Band 3 protein efficiency is compromised by treatment with Cadmium (Cd2+), an extremely toxic heavy metal known to interfere with antioxidant enzymes, energy metabolism, gene expression and cell membranes. To this end, the rate constant for SO4= uptake through Band 3 protein (accounting for velocity of anion exchange) was measured along with membrane –SH groups, Malonyldialdehyde (MDA) and Band 3 protein expression levels in Cd2+ -treated human erythrocytes (300 µM, 1 mM). Our results show that Cd2+ reduced the rate constant for SO4= uptake, with a significant increase in MDA levels at both concentrations and with a reduction in –SH groups observed after 1 mM Cd2+ treatment, whereas Band 3 protein expression levels were unchanged in both conditions. In conclusion: i) Cd2+ reduces Band 3 protein efficiency via different mechanisms depending on metal concentration and with unchanged expression levels; ii) the assessment of Band 3 protein anion exchange capability is a good tool to assay the impact of heavy metals on cell homeostasis and, possibly, useful for diagnosis and monitoring of devalopment of Cd2+ toxicity-related pathologies.

Cystathionine γ-Lyase Is Involved in the Renoprotective Effect of Brief and Repeated Ischemic Postconditioning After Renal Ischemia/Reperfusion Injury in Diabetes Mellitus

BackgroundThe aim of this study was to determine whether the protective effects of brief and repeated ischemic postconditioning (IPoC) are associated with the modulation of cystathionine γ-lyase (CSE) expression after renal ischemia/reperfusion (I/R) injury in diabetes mellitus (DM). MethodsWe subjected diabetic rats to 45 minutes of ischemia followed by reperfusion at 24 hours. Before reperfusion, diabetic rats were treated with 3 cycles of 6 seconds of reperfusion, followed by 6 seconds of ischemia. DL-Propargylglycine (PAG, a CSE inhibitor) was administered to the diabetic rats to investigate its effects on the severity of renal I/R injury in diabetes mellitus (DM). Blood samples and left kidneys were collected for the measurement of blood urea nitrogen (BUN) and serum creatinine (SCr) levels and renal pathologic changes. Western blot and immunochemistry techniques were also performed for the localization of CSE. Levels of superoxidase dismutase (SOD), malonyldialdehyde (MDA), tumor necrosis-alpha (TNF-α), and hydrogen sulfide (H2S) were quantified using commercially available kits. ResultsThe results showed that BUN and SCr levels increased on renal ischemia/reperfusion injury (RI/RI) in the DM group. Diabetic rats treated with IPoC exhibited significantly less renal damage on I/R. Kit measurements showed that IPoC could markedly inhibit the levels of MDA and TNF-α and also improve SOD and H2S levels. Western blot and immunochemistry showed that expression of CSE was downregulated on I/R in the DM group and IPoC upregulated CSE expression, whereas PAG treatment resulted in opposite effects. ConclusionOur findings show that brief and repeated IPoC increased the expression of CSE after I/R in DM, and the modulation of CSE may underlie the renoprotective effect of IPoC.

Plasma and Urine Malondialdehyde Levels of Infants with Acute Bronchopneumonia in the Assessment of Oxidative Response

Objective: Acute lower respiratory tract infections are seen as a major public health problem in many developing countries. This study was carried out in order to evaluate plasma and urine malonyldialdehyde (MDA) levels which represents the lipid peroxidation and hence of oxidative stress in infants diagnosed with acute bronchopneumonia which is a cause of high mortality and morbidity in children.Material and methods: This case-control study was carried out at the department of Paediatrics, Ministry of Health Bakirkoy Sadi Konuk Training and Research Hospital in 2005. The patient group comprised of 25 patients who were admitted to the hospital with the diagnosis of acute bronchopneumonia. The control group consisted of 10 healthy children of the same age range who had no pathological findings on physical examination. MDA values of urine and plasma samples were compared between both groups as an oxidative stress indicator.Results: The mean serum MDA value of the patient group was 3.91 ± 1.55 micromol/L and that of the control group was measured as 1.03 ± 0.1micromol/L. The difference was significantly higher (p 0.05).Conclusion: The urine MDA values on the first day of follow-up and the plasma MDA values may be used as a parameter in the diagnosis and following-up treatment of oxidative stress in the infants with acute bronchopneumonia.

Free radical scavenger edaravone produces robust neuroprotection in a rat model of spinal cord injury

We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord injury (SCI). SCI was induced by extradural compression of thoracic spinal cord. In experiment 1, 30 min prior to compression, rats received a 3 mg/kg intravenous bolus of edaravone followed by a maintenance infusion of 1 (low-dose), 3 (moderate-dose), or 10 (high-dose) mg/kg/h edaravone. Although both moderate- and high-dose edaravone regimens promoted recovery of spinal motor-evoked potentials (MEPs) at 2 h post-SCI, the effect of the moderate dose was more pronounced. In experiment 2, moderate-dose edaravone was administered 30 min prior to compression, at the start of compression, or 10 min after decompression. Although both preemptive and coincident administration resulted in significantly improved spinal MEPs at 2 h post-SCI, the effect of preemptive administration was more pronounced. A moderate dose of edaravone resulted in significant attenuation of lipid peroxidation, as evidenced by lower concentrations of the free radical malonyldialdehyde in the spinal cord 3 h post-SCI. Malonyldialdehyde levels in the high-dose edaravone group were not reduced. Both moderate- and high-dose edaravone resulted in significant functional improvements, evidenced by better Basso-Beattie-Bresnahan (BBB) scores and better performance on an inclined plane during an 8 week period post-SCI. Both moderate- and high-dose edaravone significantly attenuated neuronal loss in the spinal cord at 8 weeks post-SCI, as evidenced by quantitative immunohistochemical analysis of NeuN-positive cells. In conclusion, early administration of a moderate dose of edaravone minimized the negative consequences of SCI and facilitated functional recovery.

NARINGIN ATTENUATES METHOTREXATE INDUCED INTESTINAL INJURY AND OXIDATIVE STRESS IN WISTAR RATS

Methotrexate (MTX) is a pivot anticancer drug used for cancer therapy, rheumatic disease and psoriasis. Intestinal damage is a main toxic effect of MTX associated with villus shortening, mitotic arrest in crypt, atrophy of epithelium, disruption of mucosa, inflammation, ulcer and decline in goblet cells. The aim of present study was to investigate the protective effect of naringin on MTX induced intestinal injury and oxidative stress in wistar rats. The animals were randomly divided into five equal groups: Normal (saline 1 mL p.o.), MTX (20 mg/mg i.p on 4th day), Group III (Naringin 50 mg/kg p.o., + MTX 20 mg/kg, i.p.), IV (Naringin 100 mg/kg p.o., + MTX 20 mg/kg, i.p.) and V (Naringin 100 mg/kg p.o., alone). Rats of all groups except Group I and Group V treated with MTX in a dosage of 20 mg/mg i.p on 4th day. Jejunum tissues of each rat were isolated and subjected to antioxidants evaluation such as myeloperoxidase (MPO), glutathione peroxidise (GP-x), malonyl dialdehyde (MDA), glutathione (GSH), super oxide dismutase (SOD), catalase and histopathological study. Naringin exhibit a significant (P<0.001) protective role against MTX induced intestinal oxidative injury by elevating the GSH, SOD, catalase and suppresses the MPO and MDA level. Also, naringin successfully prevents the MTX treatment induced villus shortening, crypts damage, inflammatory infiltration, ulceration and depletion of goblets cells in experimental rats. The current findings demonstrate that naringin explored beneficial role by attenuating the MTX induced impairment in oxidative stress and jejunum injury in rats.

60 - Iron-sulfur [2Fe-2S] nitrosyl complexes as new trend in synthesis of donors of nitric oxide for anti-aging therapy

Aging is associated with dysfunctions in vascular smooth muscle cells, neurotransmission, renal and immune systems, to name just a few, many of which stems from decline in reliability of the regulatory functions of nitric oxide (NO) radicals. Our approach to the problems of anti-aging therapy is based on the iron-sulfur nitrosyl complexes as the donors of NO. Some of them demonstrate the anti-cancer properties (Sanina, Aldoshin, 2011). Moreover, the water-soluble polyvinylpyrrolidone composites containing the iron sulfur nitrosyl complexes with the antitumor and antiseptic activities were synthesized as potential long-living transport agents of NO (Shmatko et al., 2015). Here, we present geroprotective effects of Na2[Fe2(S2O3)2(NO)4]·4H2O (FeSNO) as the NO donor. Wistar male rats, 24 months age, were daily administered for 14 days intraperitoneally with FeSNO, 5 mg/kg of mass in 1.0 ml of physiological solution or with 1.0 ml of the physiological solution (control animals). The service for 605 days has proved that the administration with FeSNO increases survivorship of the rats about 30 percent as compared to the control animals. Furthermore, the rats of 7-8 months age were subjected to X-ray irradiation (5 Gy) after which the irradiated animals were daily intraperitoneally administered with FeSNO for 30 days, 5 mg/kg of mass, or with the physiological solution (control animals). Then, malonyldialdehyde (MDA) and the antioxidant enzymes superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (GPO) and glutathione reductase (GR) as the oxidative stress indicators were measured in liver, heart and brain tissues of the animals. It was revealed that the administration of FeSNO restores the negative impacts of irradiation on the level of MDA and the activities of SOD, Cat, GPO and GR. Thus, the nitrosyl complexes with the functionalized sulfur-containing ligands can be recommended as the potential drugs for anti-aging medicine. Furthermore, the polymer composites of the [2Fe-2S] nitrosyl complexes hold considerable promise as the drug delivery systems for NO-based therapy.

The induction of salt stress tolerance by propyl gallate treatment in green microalga Dunaliella bardawil, through enhancing ascorbate pool and antioxidant enzymes activity.

The effect of propyl gallate (PG), a synthetic antioxidant, on antioxidant responses and salinity tolerance was investigated in the cells of the green microalga, Dunaliella bardawil. Algal suspensions grown at three salinity levels of 1, 2, and 3M NaCl were incubated with 1mM of PG. The number of cells was significantly lower in all PG-treated cells compared to untreated controls. Despite PG-induced cell death, the fresh weight of all PG-treated cells was considerably higher than controls. PG-treated cells had enhanced antioxidant capacity because of increased levels of Chlorophyll a, β-carotene, reduced ascorbate, protein, and enzymatic activities, but accumulated lower levels of malonyldialdehyde and hydrogen peroxide compared to untreated cells. The results suggest that PG acts as a signal molecule both directly by reducing of free radical oxidants and indirectly by augmenting ascorbate pool levels, β-carotene production, and antioxidant enzymes activity to boost the capacity of antioxidant systems and radical oxygen species scavenging. Therefore, induction of salt stress tolerance by PG in D. bardawil is associated with metabolic adjustments through activation or synthesis of both enzymatic and non-enzymatic molecules involved in antioxidant systems.

To Study The Serum Vitamin –D And Oxidative Stress Status In Rheumatoid Arthritis

Aim and objectives: Rheumatoid arthritis (RA) is a chronic autoimmune systemic disease characterized predominantly by synovial inflammation, leading to joint destruction. The study was undertaken to analyze the vitamin –D and oxidative stress status in Rheumatoid arthritis
 
 Materials and methods: The Study includes Patients diagnosed as RA by using RA factor within the age group of30 to 60 years and comprised of 20 age matched control group. To assess oxidative stress, serum Malonyldialdehyde (MDA) was by thiobarbituric acid method and antioxidant level was assessed by estimation of serum vitamin C by dinitrophenyl hydrazine method. And vitamin D total is estimated by chemiluminescent immunoassay.
 Results: There is a significant decreased level of vitamin -D in the RA patients (37.58±5.7ng/ml) as compared to healthy controls (58.5±5.6ngl/ml). There is a a significant increased levels of MDA in the RA patients (7.6±1.09) as compared to healthy controls (8.4±2.8). There is a significant decreased level of vitamin -c in the RA patients (0.6±0.3mg/dl) as compared to healthy controls (1.0±0.31mg/dl).
 
 Conclusion: Low levels of Vitamin D deficiency in RA patients is associated with inflammation which leads to Increased oxidative stress status , which may lead to connective tissue degradation leading to joint and periarticular deformities in rheumatoid arthritis.

The involvement of Nrf2 in the protective effects of (-)-Epigallocatechin-3-gallate (EGCG) on NaAsO2-induced hepatotoxicity.

Arsenic exposure produces hepatotoxicity. The common mechanism determining its toxicity is the generation of oxidative stress. Oxidative stress induced by arsenic leads to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. (-)-Epigallocatechin-3-gallate (EGCG) possesses a potent antioxidant capacity and exhibits extensive pharmacological activities. This study aims to evaluate effects of EGCG on arsenic-induced hepatotoxicity and activation of Nrf2 pathway. Plasma activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were measured; Histological analyses were conducted to observe morphological changes; Biochemical indexes such as oxidative stress (Catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), reactive oxygen species (ROS)), Nrf2 signaling related genes (Nrf2, Nqo1, and Ho-1) were assessed. The results showed that EGCG inhibited arsenic-induced hepatic pathological damage, liver ROS level and MDA level. Arsenic decreases the antioxidant enzymes SOD, GPX, and CAT activity and the decrease was inhibited by treatment of EGCG. Furthermore, EGCG attenuated the retention of arsenic in liver tissues and improved the expressions of Nrf2 signaling related genes (Nrf2, Nqo1, and Ho-1). These findings provide evidences that EGCG may be useful for reducing hepatotoxicity associated with oxidative stress by the activation of Nrf2 signaling pathway. Our findings suggest a possible mechanism of antioxidant EGCG in preventing hepatotoxicity, which implicate that EGCG may be a potential treatment for arsenicosis therapy.

OXIDATIVE STRESS INCIDENCE ON THE SEVERITY OF KNEE OSTEOARTHRITIS

The aim of the study was to examine the incidence of oxidative stress on the severity of knee osteoarthritis (OA). Data were obtained from a previous pilot controlled trial among patients, diagnosed with OA in one or both knees, that were randomly assigned into two different treatment groups and were either supplemented with ascorbic acid and Vitamin E daily per os or treated with meloxicam. The following markers were estimated: A. Clinical markers: functionality of the knee (WOMAC index), pain (using a pain visual analogue scale) and severity of OA (Kellgren–Lawrence grading scale) B. Laboratory markers: total antioxidant capacity (TAC) and malonyldialdehyde (MDA) levels in the synovial fluid. The TAC of the knees was moderately correlated with the severity of OA and the level of pain whilst MDA concentration was weekly correlated. An average change of 5[Formula: see text]mM of a-tocopherol in TAC (4.6–5.5[Formula: see text]mM of a-tocopherol) defines the shift among stages of OA and the level of pain experienced by the patients. Neither TAC nor MDA were correlated with the Kellgren–Lawrence grading scale. Alleviation of oxidative stress should be a key objective for the therapeutic interventions (pharmacological and nonpharmacological) in knee OA. Even small improvements in antioxidant capacity of the synovial fluid may contribute to the patient’s quality of life and to the deceleration of the disease progression.

PROTECTIVE ROLE OF DAIDZEIN AGAINST CYCLOPHOSPHAMIDE INDUCED NEPHROTOXICITY IN EXPERIMENTAL RATS

Objective: To evaluate the protective effect of daidzein on cyclophosphamide (CPA) induced nephrotoxicity in experimental rats.Methods: The Wistar rats of either sex were randomly divided into five equal groups: Group I (normal saline 1 ml p. o.), Group II (CPA 150 mg/mg i. p), Group III (Daidzein 20 mg/kg p. o.+CPA 150 mg/kg, i. p.), Group IV (Daidzein 40 mg/kg p. o.+CPA 150 mg/kg, i. p.) and Group V (Daidzein 40 mg/kg p. o., alone). Rats of all groups except Group I and Group V treated with CPA in a dosage of 150 mg/mg i. p in the last five days of treatment. Blood samples were collected on 11th day from each rat and subjected for the evaluation of serum markers such as Serum creatinin, serum urea and serum uric acid. Kidney of each rat was excised and subjected for antioxidant parameters evaluation such as malonyl dialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase and histopathological study.Results: Daidzein explored a significant (P<0.001) role in CPA-induced nephrotoxicity by suppressing serum creatinine, serum urea and serum uric acid. Daidzein also demonstrated significant (P<0.001) protection against CPA-induced nephrotoxicity by decreasing MDA level and by elevating the GSH, SOD, catalase at different doses.Conclusions: The obtained results of present study revealed that daidzein attenuates the CPA-induced nephrotoxicity by antioxidant defence action in rats.

Cytoprotective Effects and Mechanisms of Δ-17 Fatty Acid Desaturase in Injured Human Umbilical Vein Endothelial Cells (HUVECs).

BackgroundThe beneficial effect of Δ-17 FAD is poorly understood. The aim of this study was to investigate the protective mechanism of fatty acids against atherosclerotic (AS) damage induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs), and to identify the molecular mechanisms involved.Material/MethodsThe ox-LDL was used to induce lipotoxicity in HUVECs to establish a model of oxidative injury. HUVECs were transfected with Δ-17FAD lentivirus to induce cytoprotective effects. We evaluated the alterations in cell proliferation and apoptosis, and oxidative stress index, including levels of nitric oxide (NO), malonyldialdehyde (MDA), SOD enzyme, LDH, GSH-PX, and vascular endothelial growth factor (VEGF) expression.ResultsThe ox-LDL-induced excessive cellular apoptosis of HUVECs was abrogated by upregulation of Δ-17 FAD. Importantly, Δ-17 FAD converted ω-3 polyunsaturated fatty acid ARA into ω-6 polyunsaturated fatty acid EPA. Further, Δ-17 FAD overexpression promoted the proliferation of HUVECS, and inhibited ox-LDL-induced lipid peroxidation of HUVECs. The levels of nitric oxide, GSH-PX, and SOD enzyme were increased, and the activity of MDA and LDH was suppressed by the upregulation of Δ-17 FAD. In addition, upregulation of Δ-17 FAD significantly increased VEGF expression. In vitro tube formation assay showed that Δ-17 FAD significantly promoted angiogenesis.ConclusionsThese results suggest that Δ-17 fatty acid desaturase plays a beneficial role in the prevention of ox-LDL-induced cellular damage.