High Degree Of Oxidative Stress Research Articles

Oxidative stress and DNA damage in critically ill patients with sepsis.

The aim of our study was to assess the oxidative stress and inflammatory status in critically ill patients with sepsis as well as their relationship with the level of DNA damage. The study also evaluated the influence of all analyzed parameters on the outcome of the patients. The study included 27 critically ill patients with sepsis and 20 healthy subjects. Comet Assay was used for the measurement of the level of DNA damage, expressed as genetic damage index (GDI). Both oxidative stress parameters and the antioxidant parameters were obtained spectrophotometrically. The standard laboratory methods and the appropriate autoanalyzers were performed for determination the parameters of inflammation. A higher level of oxidative stress and more pronounced inflammation were found in the patients with sepsis compared to healthy subjects. The activity of the antioxidant enzymes was statistically declined in patients with sepsis, so that the most notable differences between two groups of participants were found for the activity of superoxide dismutase (SOD) (p=0.004). Comet assay indicated that patients with sepsis had significantly higher GDI compared to healthy subjects (p<0.001), which positively correlated with the concentration of superoxide anion radical (О2-) (r=0.497, p=0.010), and nitrites (NО2-) (r=0.473, p=0.015), as well with the concentration of C reactive protein (CRP) (r=0.460, p=0.041). Regression analysis confirmed that patients' age (p=0.033), the level of О2- (p=0.007), CRP concentration (p=0.029) and GDI (p=0.001) increased the risk of lethal outcome in critically ill patients with sepsis. In conclusion, critically ill patients with sepsis have a higher degree of oxidative stress and inflammation which contribute to a higher level of DNA damage. Consequently, above mentioned parameters, including patients' age, adversely affect the outcome of critically ill patients with sepsis.

Serum Bilirubin and Markers of Oxidative Stress and Inflammation in a Healthy Population and in Patients with Various Forms of Atherosclerosis.

Oxidative stress and inflammation contribute significantly to atherogenesis. We and others have demonstrated that mildly elevated serum bilirubin levels protect against coronary and peripheral atherosclerosis, most likely due to the antioxidant and anti-inflammatory activities of bilirubin. The aim of the present study was to assess serum bilirubin and the markers of oxidative stress and inflammation in both healthy subjects and patients with various forms of atherosclerosis. The study was performed in patients with premature myocardial infarction (n = 129), chronic ischemic heart disease (n = 43), peripheral artery disease (PAD, n = 69), and healthy subjects (n = 225). In all subjects, standard serum biochemistry, UGT1A1 genotypes, total antioxidant status (TAS), and concentrations of various pro- and anti-inflammatory chemokines were determined. Compared to controls, all atherosclerotic groups had significantly lower serum bilirubin and TAS, while having much higher serum high-sensitivity C-reactive protein (hsCRP) and most of the analyzed proinflammatory cytokines (p < 0.05 for all comparisons). Surprisingly, the highest inflammation, and the lowest antioxidant status, together with the lowest serum bilirubin, was observed in PAD patients, and not in premature atherosclerosis. In conclusion, elevated serum bilirubin is positively correlated with TAS, and negatively related to inflammatory markers. Compared to healthy subjects, patients with atherosclerosis have a much higher degree of oxidative stress and inflammation.

Functional Role of Natural Antioxidants in Controlling Oxidative Stress Associated with SARS-CoV-2 Infection

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogenic coronavirus that emerged in late 2019, resulting in coronavirus disease (COVID-19). COVID-19 can be potentially fatal among a certain group of patients. Older age and underlying medical illness are the major risk factors for COVID-19-related fatal respiratory dysfunction. The reason for the pathogenicity of COVID-19 in the older age group remains unclear. Factors, such as coagulopathy, cytokine storm, metabolic disruption, and impaired T cell function, may worsen the symptoms of the disease. Recent literature has indicated that viral infections are particularly associated with a high degree of oxidative stress and an imbalance of antioxidant response. Although pharmacological management has taken its place in reducing the severity of COVID-19, the antioxidants can serve as an adjunct therapy to protect an individual from oxidative damage triggered by SARS-CoV-2 infection. In general, antioxidant enzymes counteract free radicals and prevent their formation. The exact functional role of antioxidant supplements in reducing disease symptoms of SARS-CoV-2 infection remains mostly unknown. In this review, the functional role of natural antioxidants in SARS-CoV-2 infection management is discussed in brief.

The role of ethylene signalling in the regulation of salt stress response in mature tomato fruits: Metabolism of antioxidants and polyamines

Salt stress-induced ethylene (ET) can influence the defence responses of plants that can be dependent on plant organs. In this work, the effects of salt stress evoked by 75 mM NaCl treatment were measured in fruits of wild-type (WT) and ET receptor-mutant Never ripe (Nr) tomato. Salt stress reduced the weight and size of fruits both in WT and Nr, which proved to be more pronounced in mutants. In addition, significantly higher H2O2 levels and lipid peroxidation were measured after the salt treatment in Nr as compared to the untreated control than in WT. ET regulated the key antioxidant enzymes, especially ascorbate peroxidase (APX), in WT but in the mutant fruits the activity of APX did not change and the superoxide dismutase and catalase activities were downregulated compared to untreated controls after salt treatment contributing to a higher degree of oxidative stress in Nr fruits. The dependency of PA metabolism on the active ET signalling was investigated for the first time in fruits of Nr mutants under salt stress. 75 mM NaCl enhanced the accumulation of spermine in WT fruits, which was not observed in Nr, but levels of putrescine and spermidine were elevated by salt stress in these tissues. Moreover, the catabolism of PAs was much stronger under high salinity in Nr fruits contributing to higher oxidative stress, which was only partially alleviated by the increased total and reduced ascorbate and glutathione pool. We can conclude that ET-mediated signalling plays a crucial role in the regulation of salt-induced oxidative stress and PA levels in tomato fruits at the mature stage.

Comparison of thiol disulfide values in the cord blood of patients undergoing cesarean section under spinal or general anesthesia

Background/Aim: Oxidative stress is known to increase in patients receiving anesthesia before undergoing surgery. Since newborns are more sensitive to oxygen-free radicals, the effects and characteristics of anesthesia methods that are used for pregnant women require analysis. This study aimed to evaluate the effects of spinal and general anesthesia on oxidative stress by investigating thiol disulfide and ischemia modified albumin (IMA) concentrations in the cord blood of patients undergoing cesarean section (C-section) via spinal or general anesthesia.&#x0D; Methods: This cross-sectional prospective study included 60 patients who were indicated for elective cesarean section. Patients with chronic disease, pregnancy complications and/or required emergency cesareans were not included. Group 1 (n = 30) underwent general anesthesia, and Group 2 (n = 30) underwent spinal anesthesia during their C-sections. Thiol–disulfide levels were evaluated concurrently in all blood samples taken from the umbilical artery remaining on the placental side.&#x0D; Results: The mean age (SD) of the mothers was 30.6 (4.4) years and the mean gestational age (SD) was 39.0 (0.9) weeks. Gestational age, birth weight, and first and fifth min Apgar scores of the two groups were similar. The mean (SD) native thiol (362.4 [63.8]; 323.2 [45.8]), total thiol (409.6 [70.2]; 363.5 [46.1]), and disulfide values (23.6 (5.4); 20.2 (4.3)) were significantly higher in group 1 than group 2, while the median (interquartile range [IQR]) values of IMA (0.89 (0.85-max 0.92); 0.85 (min 0.82-max 0.879) were significantly higher in group 2 than group 1 (P &lt; 0.05).&#x0D; Conclusions: As general anesthesia may cause a higher degree of oxidative stress, selecting the appropriate anesthetic technique may be especially important for risky pregnancies in which increased oxidative stress in the mother and baby may be critical for the outcome.

Possible Role of Ppar-Alpha Agonist in Attenuated Cardioprotective Effects of Ischemic Postconditioning in Diabetic Rat Heart

Background: It has been accounted for that infarct size reduction and cardioprotective effects of Ischemic Postconditioning (IPOC) have been abrogated in few pathological conditions including diabetes. Peroxisome Proliferator-Activated Receptor-Alpha (PPAR-Alpha) agonist is known to have cardioprotective effect. Therefore, the current examination researched the possible role of PPAR-Alpha Agonist in Attenuated Cardioprotective Effects of Ischemic Postconditioning in Diabetic Rat Heart. Materials and Methods: Rats were injected Alloxan Monohydrate (150/mg/kg/i.p) single dose to produced diabetes. Isolated Langendorff ’s perfused normal and diabetic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analyzed for Lactatedehydogenase (LDH) and Creatine Kinase (CK) release to evaluate the extent of cardiac injury. The oxidative stress in heart was evaluated by measuring Thiobarbituric Acid Reactive Substances (TBARS), superoxide dismutase (SOD) generation and reduced form of glutathione. Result: In the current investigation, Ischemia-reperfusion (I/R) induced oxidative stress by increasing TBARS, superoxide anion generation and the decreased form of glutathione in normal and diabetic rat heart. Moreover, I/R induced myocardial injury, was evaluated in terms of increase in, LDH and CK release in coronary effluent, and reduction in coronary flow rate in normal and diabetic rat heart. The diabetic rat heart showed enhanced I/R induced myocardial injury with high extent of oxidative stress as compared with normal rat heart subjected to I/R Six episodes of IPOC afforded cardioprotection against I/R induced myocardial injury in normal rat heart as assessed in terms of improvement of coronary flow rate and decrease of LDH, CK and oxidative stress. On other hand, IPOC mediated myocardial protection against I/R injury was nullified in diabetic rat heart. Fenofibrate (5µM), a selective agonist of PPAR alpha, its administration markedly restored the Cardioprotective potential of IPOC in diabetic rat heart. Conclusion: The current investigation presumed that, the high degree of oxidative stress produced in diabetic rat heart during reperfusion and resulting inactivation of PPAR alpha receptor might be responsible for abolishing the Cardioprotective potential of IPOC against I/R induced myocardial injury

Oxidative stress correlates well with markers of metabolic syndrome in clinically hypothyroid cases: a hospital based study in a remote tribal district

Relevance. Dislipidemia is one of the major manifestation of thyroid disease process due to alteration of metabolic parameters which are also seen in metabolic syndrome. Though oxidative stress has been implicated in both processes, controversial results have been obtained. Objective. To determine the status of lipid peroxidation product (Lpx) in the study group and identify the association of different components of metabolic syndrome. Material and Methods: 102 patients comprising of 60 healthy euthyroid controls and 42 hypothyroid patients served as the study group. Blood samples were collected for fasting blood sugar, renal parameters, lipid profile, tri-iodothyronin (T3), thyroxine (T4) and thyroid stimulating hormone (TSH). Level of lipid peroxidation in the samples was determined by monitoring the level of thiobarbituric acid like substances (TBARS) like substances. Results. The demographic parameters were significantly altered in hypothyroid patients. Systolic and diastolic blood pressure amongst both the groups was observed to have higher mean value in hypothyroid patients. The fasting blood sugar (FBS), total cholesterol, triacylglycerol, low density lipoprotein (LDL) and high density lipoprotein (HDL) in the hypothyroid was significantly higher than euthyroid control groups. The most frequent alteration in the hypothyroid patients was rise in SBP (95 %), Hypertriglyceridemia (50 %) and raised waist circumference (48 %) and DBP (42 %). A fourfold rise in Lpx was observed in hypothyroid subjects (p0.001). Robust positive association was observed between TSH and Lpx. Multiple linear regressions revealed strongest and statistically significant association between serum serum thyroid stimulating hormone and waist circumference. Conclusion. The hypothyroid patients have significant higher degree of oxidative stress and the components of metabolic syndrome. They are the candidates for preventive health intervention.

PSXV-14 Level of spontaneous oxidative modification of sperm plasma proteins in stallions of different ages

Abstract The objective of the study was to assess the level of spontaneous oxidative modification of sperm plasma proteins (OMP) in young and mature stallions as indicators of the severity of oxidative stress. Sperm from 12 stallions aged 14–18 years (average age 15.8±1.9 years) (Group I) and 12 stallions aged 3–5 years (average age 4.3±0.6 years; Group II) was obtained during the breeding season (February-May). Each ejaculate was evaluated by volume, concentration, total number of spermatozoa, as well as by the progressive motility and survival of spermatozoa in diluted sperm during its hypothermic storage at +4°C. For a quantitative assessment of the OMP level, a spectrophotometric analysis of 2,4-dinitrophenylhydrazones formed during the interaction of carbonyl derivatives of proteins with 2,4-dinitrophenylhydrazine was carried out (SF-2000, Russia). The level of aldehyde- and ketone-dinitrophenylhydrazones of neutral (ADNPHn, KDNPHn) and basic (ADNPGb, KDNPGb), and the total level of OMP (S OMP) was measured. Significance of differences was assessed by the Mann-Whitney test, the results were statistically significant at P ≤ 0.05. The total level of spontaneous OMP of sperm plasma in aged stallions is statistically significantly higher than in young stallions (531.7 and 384.3 Uod/g protein, respectively, P &amp;lt; 0.05). This indicates a higher degree of oxidative stress in Group I, a more significant damage to the amino acid residues of sperm plasma proteins. In Group I a shift in the absorption spectrum towards neutral aldehyde derivatives (367.6 and 255.8 Uod/g protein, respectively, P &amp;lt; 0.05) was noted. We assume that the pro-oxidant systems in a stallion body increasingly prevail over the protective ones with the age. This leads to an increase in the level of OMP in the sperm and a decrease in the survival of spermatozoa during the hypothermic storage of diluted sperm. Authors acknowledge financial support from Russian Science Foundation, Grant No: 20-16-00101.

P-BN005. Maternal vitamin B12 deficiency is associated with increased oxidative stress and DNA damage in brain regions of C57BL/6 mouse offspring

Introduction . Maternal micronutrient deficiencies are predominant in developing countries. Vitamin B12 deficiency is common in women, especially during child-bearing age. Maternal vitamin B12 deficiency is known to have a profound impact on the developing fetus and programs it to a number of complex adult-onset disorders like cardiovascular diseases, diabetes, neurological disturbances, etc. We hypothesized that increased oxidative stress and reduced activity of antioxidant enzymes along with DNA damage in the brain are associated with the etiology of these complications. As little is known about the effects of maternal vitamin B12 restriction on brain regions of the offspring, we have focused particularly on the cerebral cortex and hippocampus in our study. Methods . Female, weaning C57BL/6 mice received ad libitum for 4 weeks a control diet (American Institute of Nutrition-76A) or the same with restriction of vitamin B12. After confirming the deficiency, the mice were allowed to breed with control males to obtain the F1 generation offspring. The different parameters related to oxidative stress and DNA damage were assessed at 3 months of age of the offspring. Results . Interestingly, offspring born to mice fed on vitamin B12 restricted diet had a significantly higher degree of oxidative stress in both the cerebral cortex and hippocampus as reflected by their increased levels of lipid peroxidation and protein oxidation. Also, the activity of antioxidant enzymes (superoxide dismutase and catalase) was diminished in both the brain regions of offspring born to mice fed on vitamin B12 restricted diet. DNA damage in the form of single and double-stranded DNA breaks were also increased in the cerebral cortex and hippocampus of mice offspring born to vitamin B12 restricted dams. Conclusion . To conclude, maternal vitamin B12 deficiency is associated with increased oxidative stress in the brain of young offspring, which further leads to DNA damage in the brain.

Oxidative stress markers, thioredoxin 1 and 8-isoprostane, in relation to ischemic time in patients with ST‑segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

The extent of ischemia-reperfusion injury (IRI) significantly affects the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). Excessive generation of reactive oxygen species during ischemia and subsequent reperfusion leads to cellular necrosis and apoptosis. These processes contribute to the impairment of microcirculation and the no-reflow phenomenon, development and progression of left ventricular remodeling and failure. Out of numerous factors affecting the complex process of IRI, the duration of ischemia is of major importance. Prolonged ischemia has been associated with higher degree of oxidative stress, but only scarce evidence is available up to date.2 Our goal was to evaluate selected markers of oxidative stress in relation to reperfusion via primary percutaneous coronary intervention (pPCI) and their potential correlation with the duration of ischemia, defined as time delay between symptom onset and reperfusion.

Optimal Nitrogen Supply Ameliorates the Performance of Wheat Seedlings under Osmotic Stress in Genotype-Specific Manner.

Strategies and coping mechanisms for stress tolerance under sub-optimal nutrition conditions could provide important guidelines for developing selection criteria in sustainable agriculture. Nitrogen (N) is one of the major nutrients limiting the growth and yield of crop plants, among which wheat is probably the most substantial to human diet worldwide. Physiological status and photosynthetic capacity of two contrasting wheat genotypes (old Slomer and modern semi-dwarf Enola) were evaluated at the seedling stage to assess how N supply affected osmotic stress tolerance and capacity of plants to survive drought periods. It was evident that higher N input in both varieties contributed to better performance under dehydration. The combination of lower N supply and water deprivation (osmotic stress induced by polyethylene glycol treatment) led to greater damage of the photosynthetic efficiency and a higher degree of oxidative stress than the individually applied stresses. The old wheat variety had better N assimilation efficiency, and it was also the one with better performance under N deficiency. However, when both N and water were deficient, the modern variety demonstrated better photosynthetic performance. It was concluded that different strategies for overcoming osmotic stress alone or in combination with low N could be attributed to differences in the genetic background. Better performance of the modern variety conceivably indicated that semi-dwarfing (Rht) alleles might have a beneficial effect in arid regions and N deficiency conditions.

The protective effect of fibroblast growth factor‐21 in alcoholic cardiomyopathy: a role in protecting cardiac mitochondrial function

Alcoholic cardiomyopathy (ACM) resulting from chronic alcohol misuse is one of the main contributors leading to heart failure and cardiovascular mortality. Fibroblast growth factor 21 (FGF21) is a well-established cardioprotective factor. We aimed to study the role of FGF21 in experimentally induced models and clinical affected patients with cardiac damage due to chronic alcohol consumption. We found that circulating FGF21 levels and cardiac FGF21 and β-klotho protein levels were increased in subjects with chronic alcohol consumption. As an experimental model of ACM, we fed wild-type and Fgf21 knockout (Fgf21-/- ) mice with a 4% alcohol liquid diet for 4 and 12 weeks. FGF21 circulating levels and FGF21 expression in the myocardium were also increased in wild-type mice after chronic alcohol intake. Fgf21-/- mice develop a higher degree of cardiac hypertrophy, fibrosis, and cardiac dysfunction after chronic alcohol consumption than wild-type mice. Moreover, the myocardium of Fgf21-/- mice showed signs of metabolic deregulation, oxidative stress, and mitochondrial dysfunction after alcohol intake. Finally, human cardiac biopsies from patients with chronic alcohol consumption developing ACM presented a higher degree of oxidative stress which positively correlated with the FGF21 protein levels in the myocardium. We conclude that plasma levels and cardiac myocyte FGF21 expression were induced in response to chronic alcohol consumption. The lack of FGF21 aggravated cardiac damage produced by ACM, in association with enhanced mitochondrial and oxidative stress, thus pointing to FGF21 as a protective agent against development of alcohol-induced cardiomyopathy. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Evaluation of oxidant/antioxidant status, metabolic profile and milk production in cows with metritis

BackgroundThe aim of the study was to evaluate oxidant/antioxidant status in 21 Holstein dairy cows with metritis compared to 8 healthy controls. Blood samples were taken during the first 21 days postpartum. Malondialdehyde (MDA), a marker of oxidative stress, total antioxidant status (TAS) and antioxidant parameters such as glutathione peroxidase (GPx), selenium (Se), vitamins A and E and beta-carotene were determined from all cows. The differences in beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), calcium, bilirubin concentrations and aspartate aminotransferase (AST) activity were also monitored, as were milk production and milk composition. Metritis was defined by an unpleasant discharge of varying color (milky-grey/brown/sanguineous) and consistency (muco-purulent/purulent/watery) and by the presence of increased temperature (> 38.5 °C) in cows within 21 days postpartum. Rectal examination revealed increased uterine size, thickened uterine wall and increased uterine tone. The affected cows had significantly reduced daily milk production. Additionally, hematological parameters and haptoglobin concentration were also measured in metritic cows.ResultsHigher MDA concentration (P < 0.001) was recorded in cows with metritis, while vitamin A and vitamin E concentrations were lower (P < 0.01) compared to healthy cows. Higher BHB (P < 0.05), NEFA (P < 0.05), AST (P < 0.05) and bilirubin (P < 0.001) concentrations was recorded in cows with metritis as compared to the control group. Significant differences in beta-carotene concentration, GPx activity, and Se, TAS and Ca concentrations in cows with metritis compared to control group were not observed in the present study (P > 0.05). Milk production was decreased in the cows with metritis (P < 0.001) and alterations in milk composition were also observed in metritic cows as compared to healthy cows.ConclusionsThe results of the study showed that cows with metritis in early postpartum are exposed to a higher degree of oxidative stress and that the incidence of metritis can negatively affect milk production in dairy cows.

Proteomic and Ultrastructural Analysis of Cellulite-New Findings on an Old Topic.

Background: Cellulite is a condition in which the skin has a dimpled lumpy appearance. The main causes of cellulite development, studied until now, comprehends modified sensitivity to estrogens, the damage of microvasculature present among dermis and hypodermis. The differences of adipose tissue architecture between male and female might make female more susceptible to cellulite. Adipose tissue is seen to be deeply modified during cellulite development. Our study tried to understand the overall features within and surrounding cellulite to apply the best therapeutic approach. Methods: Samples of gluteal femoral area were collected from cadavers and women who had undergone surgical treatment to remove orange peel characteristics on the skin. Samples from cadavers were employed for an accurate study of cellulite using magnetic resonance imaging at 7 Tesla and for light microscopy. Specimens from patients were employed for the proteomic analysis, which was performed using high resolution mass spectroscopy (MS). Stromal vascular fraction (SVF) was obtained from the samples, which was studied using MS and flow cytometry. Results: light and electron microscopy of the cellulite affected area showed a morphology completely different from the other usual adipose depots. In cellulite affected tissues, sweat glands associated with adipocytes were found. In particular, there were vesicles in the extracellular matrix, indicating a crosstalk between the two different components. Proteomic analysis showed that adipose tissue affected by cellulite is characterized by high degree of oxidative stress and by remodeling phenomena. Conclusions: The novel aspects of this study are the peculiar morphology of adipose tissue affected by cellulite, which could influence the surgical procedures finalized to the reduction of dimpling, based on the collagen fibers cutting. The second novel aspect is the role played by the mesenchymal stem cells isolated from stromal vascular fraction of adipose tissue affected by cellulite.

Possible mechanism involved in attenuated cardioprotective effects of ischemic post-conditioning in hyperglycaemic rat heart

The present study aimed to investigate the possible role of JAK-2 in attenuated cardio protective effects of ischemic post-conditioning (IPOC) in Hyperglycaemic rat heart. Experimental hyperglycaemia was induced by Alloxan monohydrate (100 mg/kg, i.p). Isolated normal & hyperglycaemic rat heart mounted on Langendorff's apparatus was subjected to 30 min of global ischemia followed by 120 min of reperfusion. Six episodes of ischemia followed by reperfusion with Kreb's-Henseleit solution were given each comprising of 10 s to produce IPOC. Ischemia-reperfusion (I/R) induced oxidative stress by increasing thiobarbituric acid reactive substances (TBARS), superoxide-dismutase (SOD) and decreasing reduced form of glutathione in normal and hyperglycaemic rat heart. Furthermore, I/R induced myocardial injury which were indexed by increased in LDH, CK-MB release in coronary effluent, myocardial infract size, and decreased in coronary flow rate in normal and hyperglycaemic rat heart. Extent of myocardial injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC) staining. The hyperglycaemic rat heart showed enhanced I/R-induced myocardial injury with noted high degree of oxidative stress. Treatment with Tyrphostin-AG490 (5 μM), a selective inhibitor of JAK-2 markedly restored the cardioprotective potential of IPOC in hyperglycaemic rat heart. The high degree of oxidative stress produced in hyperglycaemic rat hearts during reperfusion may activate JAK-2, which may be implicated in the observed paradoxically abrogated cardioprotective effect of IPOC. It is concluded that the high degree of oxidative stress produced in hyperglycaemic rat heart during reperfusion may activate JAK-2, may be implicated in the observed paradoxically abrogated cardioprotective effect of IPOC.

Role of fibrates in attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart

The present study has been designed to investigate the beneficial role of Fenofibrate in attenuated the cardioprotective effect of ischemic preconditioning (IPC) in hyperlipidemic (Hpl) rat heart. Experimental Hpl was produced by feeding high fat diet to rats for a period of 28 days. Isolated langendorff's perfused normal and Hpl rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. The myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase-MB release to assess the extent of cardiac injury. Moreover, the oxidative stress in heart was assessed by measuring thiobarbituric acid reactive substance, superoxide anion generation and reduced form of glutathione. Moreover, I/R produced myocardial injury, which was assessed in terms of increase in myocardial infarct size, LDH and CK-MB release in coronary effluent and decrease in coronary flow rate. Four episodes of IPC (5 min each) afforded cardioprotection against I/R-induced myocardial injury in normal rat heart. On the other hand, IPC mediated myocardial protection against I/R-injury was abolished in Hpl rat heart. However, Treatment with Fenofibrate (100 mg/kg/day, i.p.) as agonists of PPAR-α have not affected the cardioprotective effect of IPC in normal rat heart, but its treatment markedly restored the cardioprotective potentials of IPC in Hpl rat heart. It is noted that the high degree of oxidative stress produced in Hpl rat heart during reperfusion and consequent down regulation of PPAR-α may be responsible to abolish the cardioprotectivepotentials of IPC.

Evaluation of urinary 8-hydroxy-2-deoxyguanosine level in experimental Alzheimer's disease: Impact of carvacrol nanoparticles.

The present study aimed to compare the effect of carvacrol essential oil and carvacrol nanoemulsion against experimental Alzheimer's (AD). Forty male albino rats were used and divided into four groups as follow: control, AlCl3 induced AD, carvacrol oil treated and carvacrol nanoemulsion treated groups. Brain nor-epinephrine, serotonin and dopamine were analyzed by high performance liquid chromatography (HPLC). Levels of brain Thiobarbituric acid-reactive substances (TBARS), Superoxide dismutase (SOD), reduced glutathione (GSH), cholinesterase, and advanced oxidation protein product (AOPP) were evaluated. Urinary 8-hydroxyguanosine (8-OHdG) level was evaluated by HPLC. Brain Cyclooxygenase 1 and 2 (COX 1and 2) were analyzed by immunohistochemistry. AD induced by AlCl3 in rats was depicted by the significant increase in the neurotransmitters levels which is accompanied with high degree of oxidative stress that was revealed in the elevated level of urinary 8-OHdG along with significant elevation in AOPP, TBARS, and cholinesterase levels and a significant decrease in SOD and GSH; these results are confirmed by immunohistochemistry analysis of COX 1 and 2. On the other hand, the treatment with carvacrol oil and carvacrol nanoemulsion were capable of mitigate effects mediated by AlCl3 administration in treated rats. While the treatment with both approached succeeded to retract the negative impact of AlCl3; but the effect of carvacrol nanoemulsion was more notable than the essential oil. Carvacrol oil and carvacrol nanoemulsion were eminent to overturn AlCl3 induced brain AD which could be imputed to antioxidant and anti-inflammatory capabilities of carvacrol to alter oxidative stress effect. In extension; carvacrol nanoemulsion were evident to give more effective and efficient way in carvacrol delivery to pass through blood brain barriers and ameliorate brain changes.

Comparative Evaluation of Oxidative Stress in Type-2 Diabetes Mellitus in Relation to Controlled Vs Uncontrolled Diabetes

Background: Type 2 Diabetes Mellitus (T2DM) is associated with the production of excess free radicals which are not neutralised by available antioxidants thereby, leading to oxidative stress (OS). The extent of oxidative damage and resulting diabetic complications may be determined by the degree of hyperglycemia viz; controlled vs uncontrolled T2DM. Aim: To evaluate and compare oxidative stress in T2DM patients with good glycemic control vs uncontrolled T2DM, by estimating malondialdehyde (MDA, index of lipid peroxidation), ferric acid reducing ability of plasma (FRAP as total antioxidant capacity, TAC). Methods: The study included 50 healthy controls (Gp I) and 100 T2DM patients which were further divided into: Gp II having good glycemic control (HbA1c ≤ 7.0%) and Gp III with uncontrolled T2DM (HbA1c >7.0%)(n=50 each). Fasting & post-prandial plasma glucose, HbA1c, MDA, FRAP & hsCRP were estimated using standard methods. Result: MDA was significantly higher and FRAP was significantly lower in T2DM patients as compared to healthy controls. Further, T2DM patients (Gp III) with uncontrolled hyperglycemia had higher degree of oxidative stress vs Gp II patients with good glycemic control. Moreover there was: i) A significant positive correlation between HbA1c & MDA (p<0.001),& ii) Significant negative correlation between HbA1c & FRAP and MDA & FRAP (p<0.001) in T2DM patients. Conclusion: Oxidative stress in T2DM patients is directly proportional to the degree of hyperglycemia measured as HbA1c.Therefore it is important to maintain tight glycemic control in T2DM patients (HbA1c ≤ 7%), to decrease oxidative stress and thereby delay the onset of diabetic complications.

Combination of Coenzyme Q10 Intake and Moderate Physical Activity Counteracts Mitochondrial Dysfunctions in a SAMP8 Mouse Model.

Aging skeletal muscles are characterized by a progressive decline in muscle mass and muscular strength. Such muscular dysfunctions are usually associated with structural and functional alterations of skeletal muscle mitochondria. The senescence-accelerated mouse-prone 8 (SAMP8) model, characterized by premature aging and high degree of oxidative stress, was used to investigate whether a combined intervention with mild physical exercise and ubiquinol supplementation was able to improve mitochondrial function and preserve skeletal muscle health during aging. 5-month-old SAMP8 mice, in a presarcopenia phase, have been randomly divided into 4 groups (n = 10): untreated controls and mice treated for two months with either physical exercise (0.5 km/h, on a 5% inclination, for 30 min, 5/7 days per week), ubiquinol 10 (500 mg/kg/day), or a combination of exercise and ubiquinol. Two months of physical exercise significantly increased mitochondrial damage in the muscles of exercised mice when compared to controls. On the contrary, ubiquinol and physical exercise combination significantly improved the overall status of the skeletal muscle, preserving mitochondrial ultrastructure and limiting mitochondrial depolarization induced by physical exercise alone. Accordingly, combination treatment while promoting mitochondrial biogenesis lowered autophagy and caspase 3-dependent apoptosis. In conclusion, the present study shows that ubiquinol supplementation counteracts the deleterious effects of physical exercise-derived ROS improving mitochondrial functionality in an oxidative stress model, such as SAMP8 in the presarcopenia phase.

Advanced glycation end products (AGEs) and cardiovascular dysfunction: focus on high molecular weight AGEs.

Advanced glycation end products (AGEs) are a group of proteins and lipids becoming glycated and oxidized after persistent contact with reducing sugars or short-chain aldehydes with amino group and/or high degree of oxidative stress. The accumulation of AGEs in the body is a natural process that occurs with senescence, when the turnover rate of proteins is reduced. However, increased circulating AGEs have been described to arise at early lifetime and are associated with adverse outcome and survival, in particular in settings of cardiovascular diseases. AGEs contribute to the development of cardiac dysfunction by two major mechanisms: cross-linking of proteins or binding to their cell surface receptor. Recently, growing evidence shows that high-molecular weight AGEs (HMW-AGEs) might be as important as the characterized low-molecular weight AGEs (LMW-AGEs). Here, we point out the targets of AGEs in the heart and the mechanisms that lead to heart failure with focus on the difference between LMW-AGEs and the less characterized HMW-AGEs. As such, this review is a compilation of relevant papers in the form of a useful resource tool for researchers who want to further investigate the role of HMW-AGEs on cardiac disorders and need a solid base to start on this specific topic.