Plasma Protein Carbonyl Research Articles

Bioavailability of l-methionine relative to dl-methionine in Broiler chickens

This study was aimed to estimate the relative bioavailability (RBA) of l-methionine (l-Met) to dl-methionine (dl-Met) in broiler chickens from 1 to 21 d of age. A total of 1664 one-day-old broiler chicks were randomly divided into 13 groups with 8 replicates per group. The basal diet contained 60% of the NRC requirement for Met. Birds in treatment groups were fed the basal diet supplemented with graded levels of dl- or l-Met, resulting in the dietary content of Met at 75%, 80%, 85%, 90%, 95% and 100% of the NRC requirement, respectively. Results showed that there were linear increases (p < .05) in average daily gain (ADG), average daily feed intake, feed efficiency (FE), eviscerated weight, breast muscle weight and leg muscle weight in response to the increasing supplementation of either dl- or l-Met, which also linearly reduced (p < .05) plasma uric acid and protein carbonyl contents. Compared with dl-Met, l-Met addition resulted in elevations (p < .05) in ADG and FE, along with leg muscle yield of birds. A lower (p < .05) content of urea nitrogen with a higher (p < .05) content of uric acid in plasma were observed in the birds supplemented with l-Met compared with dl-Met. Slope-ratio assay revealed that the RBA of l-Met to dl-Met for ADG and FE were 141.5% and 189.1%, respectively. And the respective values were calculated as 122.9% and 116.8% when based on eviscerated weight and breast muscle weight as the response criteria. However, the above RBA estimates except for FE did not differ from 100%. Collectively, supplemental l-Met had a higher bioavailability for FE of broilers relative to dl-Met during the first 3 weeks of life.Highlightsl-methionine addition has an advantage over dl-methionine for supporting the growth performance of broiler chickens in early age.The relative bioavailability of l-Met to dl-Met for feed efficiency of broiler chickens during the first 21 days post-hatch was calculated as 189.1% that differs from 100%.

Parenteral L-Arginine Improves Mitochondrial Function in Children with Sickle Cell Disease Admitted for Vaso-Occlusive Pain Episodes

Introduction: Vaso-occlusive pain episodes (VOE) are the leading cause of emergency department visits and hospitalization in patients with sickle cell disease (SCD). There is currently no standard therapy for treating the underlying causes of VOE; supportive care & symptomatic pain relief with parenteral opioids is the mainstay of therapy. Prior work by Morris & colleagues has demonstrated that patients in VOE show depleted concentrations of plasma L-arginine (Arg), and that supplementation with Arg significantly decreases total parenteral opioid use and improves pain scores during hospitalization in these patients (Morris et al 2013, Haematologica). The mechanisms by which Arg mediates these positive effects remain unclear, but are potentially due to its ability to modulate metabolism through increased Arg transport or affect vascular signaling through the stimulation of nitric oxide production. The Shiva lab has previously demonstrated that platelet mitochondrial function is altered in patients with SCD compared to healthy controls (Cardenas et al 2014, Blood). This alteration is manifested as a decrease in mitochondrial electron transport Complex V (ATP Synthase) activity, which leads to decreased respiration and increased detrimental oxidant production. Here we hypothesized that treatment of SCD patients in VOE with Arg increases mitochondrial function.Methods: In a pharmacokinetic study, 10 subjects with Hb-SS or Sb0-thalassemia hospitalized for VOE (age 14±3 years, 70% male, 80% Hb-SS) were randomized to treatment utilizing one of 3 dosing schemes of L-arginine: 1) 100mg/kg IV three times/day (n=3); 2) loading dose (200mg/kg) then 100mg/kg three times/day (n=4); or 3) loading dose (200mg/kg) followed by continuous infusion (300mg/kg/day) until discharge (n=3). Platelet rich plasma was isolated & stored at baseline & discharge for each subject & mitochondrial electron transport complex activities, protein expression, as well as protein carbonyls were measured.Results: Compared to a cohort of SCD patients in steady state, all subjects in VOE had a significantly decreased complex V activity (Fig 1A). Notably, complex V activity was increased at discharge in subjects with VOE treated with Arg in all three dosing schemes. However, the increase in complex V activity was greatest when utilizing a loading dose. (Fig 1B, p<0.001). While complex IV & citrate synthase activities were not changed in platelets from subjects with VOE compared to SCD patients in steady state (data not shown), the activities of these enzymes were also significantly increased in VOE subjects after Arg treatment when utilizing a loading dose( Fig 1C-D, p<0.01). These changes with Arg do not appear to be due to increased mitochondrial number as quantification of mitochondrial DNA before and after Arg was not different (Fig 1E). Complex V protein expression was also unchanged after Arg treatment (data not shown). However, Arg treatment did significantly decrease levels of protein carbonyls in the platelet rich plasma across all treatment dosing schemes (Fig 1F, p<0.01 in all dosing groups), suggesting a decrease in oxidative stress.Conclusion: These data demonstrate for the first time that Arg supplementation increases mitochondrial activity and decreases oxidative stress in children with SCD and VOE. Our prior study showed that complex V inhibition leads to increased mitochondrial oxidant production in platelets from SCD patients. The improvement in complex V function & decreased oxidative markers observed with Arg treatment are consistent with Arg-induced decrease in mitochondrial oxidant generation. However, Arg treatment potentially regulates other oxidant sources and could decrease overall oxidative stress in SCD patients. Arg therapy has been reported to improve symptoms associated with MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) suggesting an impact of arginine on mitochondrial activity that may be beneficial for patients with SCD. With the recent FDA approval of L-glutamine, which is an Arg prodrug, this is also a potential consequence of glutamine that warrants further study. This increase in mitochondrial function may mechanistically contribute to decreased pain and ultimately less opioid requirement after IV Arg treatment in SCD, as well as have further implications for improved metabolism and oxidative signaling in these patients. DisclosuresDampier:Pfizer: Research Funding. Morris:Pfizer: Consultancy; MAST Therapeutics: Research Funding; UCSF-Benioff Children's Hospital Oakland: Patents & Royalties: For nutritional supplement licensed to Lifetrients; Calithera: Consultancy; FDA: Research Funding; NIH/NHLBI: Research Funding.

Identification of differences in the formation of plasma glycated proteins between dogs and humans under diabetes-like glucose concentration conditions

Dogs have been proposed as a translational model and used for studying aging, diabetes, and diabetes-related complications in humans. However, no studies have ever compared the glycation of plasma proteins between dogs and humans under similar experimental conditions. Thus, the aim of this study was to fill this gap by comparing the plasma protein glycation patterns of dogs and humans in an ex-vivo system. Canine and human plasma samples were incubated with glucose at concentrations comparable to those observed in diabetic patients. The final glucose plasma concentration resulted in similar glucose:albumin ratios in both species. Glycated proteins were evaluated by measuring the content of fructosamine, protein carbonyls, and the formation of advanced glycation end-products (AGEs). The concentrations of fructosamine and protein carbonyls in canine and human plasma increased in a glucose concentration-dependent manner (P < 0.0001). Of note, the relative increment of fructosamine and protein carbonyl content and AGE formation was always higher in human than in dog plasma. Our results reveal that the plasma glycation processes in dogs and humans are not similar. These novel findings could contribute to improve our understating about canine and human diabetes as well as other condition associated in the glycation of proteins.

DNA damage and protein oxidation associated with ageing correlate with cognitive dysfunction in a Malaysian population

Ageing is associated with increased oxidative stress accompanied by cognitive decline. The aim of this study was to evaluate oxidative stress biomarkers and their possible relationship with cognitive performances during ageing among the Malay population. Approximately 160 healthy Malay adults aged between 28 and 79 years were recruited around Selangor and Klang Valley. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA), forward digit span (FDS), backward digit span (BDS), digit symbol, Rey Auditory Verbal Learning Test immediate recalled [RAVLT(I)] and delayed recalled [RAVLT(D)], and visual reproduction immediate recalled (VR-I) and delayed recalled (VR-II). DNA damage, plasma protein carbonyl and malondialdehyde (MDA) levels were also determined. Cognitive function test showed significant lower scores of MoCA, BDS, RAVLT(I), RAVLT(D), digit symbol, VR-I, and VR-II in the older age group (60 years old) compared with the 30-, 40-, and 50-year-old group. The extent of DNA damage was sequential with age: 60 > 50 > 40 > 30, whereas protein carbonyl was higher in 40-, 50-, and 60-year-old groups compared with the youngest group (30 years old). However, the MDA level was observed unchanged in all age groups. Approximately 21.88% of the participants had cognitive impairment. Multiple logistic regression analysis revealed that DNA damage and protein carbonyl levels are predictors for cognitive impairment in healthy Malays. In conclusion, cognitive decline occurred in healthy adult Malay population at an early age of 30 years old with corresponding higher DNA damage and protein oxidation.

P-110 - Centenarian offspring: A model for understanding healthy aging

Centenarians exhibit extreme longevity showing a compression of morbidity. We showed previously that microRNA expression profiles and plasma protein carbonylation in centenarians and young people are similar, whereas they are very different from that found in old individuals. This suggests that centenarians have a better control of homeostasis and are protected against oxidative damage. In this study, we aimed to determine if such characteristic microRNA expression profile and lower protein oxidation status in centenarians may be inherited by their offspring. For this purpose, we collected plasma and peripheral blood mononuclear cells from 90 septuagenarians, 68 centenarians and 46 centenarian offspring. MicroRNA expression profile was performed using the Genechip miRNA 2.0 Array and protein carbonylation by OxyBlot TM Protein Oxidation Detection kit. Our results showed that microRNA expression pattern in centenarians is similar to centenarian offspring and different to septuagenarians. We observed a significant decrease in plasma protein carbonylation levels in centenarians and centenarian offspring when compared to septuagenarians. In conclusion, centenarian offspring resemble centenarian characteristics, and could be a model of healthy aging in humans.

Effects of exhaustive exercises, with different intensities, on oxidative stress markers in rat plasma and skeletal muscle

Summary Objectives The purpose of this study was to examine the effects of exhaustive exercises, with different intensities, on oxidative stress markers in rat plasma and skeletal muscle. Methods Male Sprague-Dawley rats (n = 24) were randomly divided into the following four groups: control (CON), low-intensity exercise (LE), high-intensity interval exercise (HE) and incremental exercise (IE). The animals in the latter three groups performed exercises in which they ran until exhaustion as follows: Animals in the LE group ran at 20 m/min (6° graded); the HE group ran at 40 m/min for 30 s (0° graded) with a rest interval of 60 s between each run; and the IE group ran at 15 m/min (6° graded), initially, with the running speed gradually increased by 5 m/min, every 10 min. Immediately following the exercise, a blood sample was drawn, and followed by the gastrocnemius muscle and liver were quickly removed. These samples were analysed for lactate concentration, oxidative stress markers, and glycogen contents. Results Plasma oxidative stress markers in the LE and HE groups demonstrated no change, while plasma protein carbonyl (PC) levels and total antioxidant capacity (TAC) in the IE group were significantly increased compared with the CON group (P Conclusion Incremental exhaustive exercise elevates the plasma PC levels and TAC, but does not change skeletal muscle oxidative stress markers in rats.

The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial.

Oxidative stress plays a pivotal role in the pathogenesis of type 2 diabetes (T2D). In vitro and animal studies have shown that resveratrol exerts an antioxidant effect, but clinical trials addressing this effect in patients with T2D are limited. The aim of this study was to determine whether resveratrol supplementation affects oxidative stress markers in a randomized, placebo-controlled, double-blind clinical trial. A total of 48 patients with T2D randomly were assigned to receive 800mg/day resveratrol or placebo for 2months. Plasma total antioxidant capacity, malondialdehyde concentration, protein carbonyl and total thiol contents, intracellular superoxide anion (O2-·) and hydrogen peroxide (H2O2) in PBMCs, the expression of genes involved in oxidative stress responses (Nrf2, SOD, Cat, HO-1, RAGE, NOS) in PBMCs, and metabolic and anthropometric parameters were measured at the baseline and at the trial end. Compared with the placebo group, resveratrol reduced plasma protein carbonyl content and PBMCs O2-· level and significantly increased plasma total antioxidant capacity and total thiol content. Furthermore, the expression of Nrf2 and SOD was significantly increased after resveratrol consumption. Resveratrol had no significant effects on the metabolic and anthropometric parameters except for a significant reduction in weight, BMI, and blood pressure levels. Resveratrol was well tolerated, and no serious adverse event was occurred. Our study demonstrated that 8weeks of supplementation with 800mg/day resveratrol has an antioxidant effect in the blood and PBMCs of patients with T2D. Clinical Trial Registry number and website IRCT registration number: IRCT2015072523336N1 and http://en.search.irct.ir/view/24752 .

Effect of scuba diving on the oxidant/antioxidant status, SIRT1 and SIRT3 expression in recreational divers after a winter nondive period

The aim of this study was to examine the effects of scuba diving on oxidative damage markers in erythrocytes and plasma, antioxidant system in peripheral blood mononuclear cells (PBMCs), as well as sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3) gene expressions in recreational divers after a winter nondive period (at least 5 months). For that purpose, 17 male recreational divers performed an immersion at a depth of 30 m for 30 min. Blood samples were collected immediately before and after diving, 3 and 6 h after diving. Erythrocyte lipid peroxidation measured by thiobarbituric-reactive substances (TBARS) method was significantly increased immediately after diving, but returned to the baseline 6 h after diving, while no significant change was found for plasma TBARS and protein carbonyl derivates in both plasma and erythrocytes. Diving-induced catalase (CAT), superoxide dismutase 2 (SOD2), and consequently total superoxide dismutase (SOD) activities in the PBMC samples (significantly increased immediately after diving, reached the maximum activities 3 h after diving, while 6 h after diving only CAT activity remained significantly increased). No significant change was observed for SOD1 activity and gene expression, as well as SOD2 expression, while CAT and SIRT1 expressions were slightly decreased immediately after diving and 3 h after diving. Interestingly, SIRT3 expression was significantly increased 6 h after diving. In conclusion, after the first dive to 30 m after a nondive season, activation of antioxidant defence was not sufficient to prevent oxidative damage, while SIRT3 upregulation could be a step towards an adaptive response to the diving.

Anti‐Inflammatory and Antioxidant Actions of Methyl Jasmonate Are Associated with Metabolic Modifications in the Liver of Arthritic Rats

Methyl jasmonate (MeJA) is a fatty acid-derived cyclopentanone which shares structural similarities with prostaglandins and has been under study as a promising anti-inflammatory agent. This study investigated the actions of MeJA on systemic inflammation and oxidative status in rats with adjuvant-induced arthritis, a model for rheumatoid arthritis. MeJA (75 to 300 mg·kg−1) was administrated orally during 18 days after arthritis induction with Freund's adjuvant. Articular and systemic inflammation was greatly increased in arthritic rats, likewise the oxidative stress in plasma and liver. The hepatic glucokinase activity and glycolysis were increased in arthritic rats. MeJA decreased most inflammatory parameters and abolished the increased protein carbonylation in plasma and liver, diminished the increased hepatic ROS content, and restored the hepatic GSH/GSSG ratio in arthritic rats. However, the MeJA treatment decreased the hepatic glucokinase activity and glycolysis and stimulated mitochondrial ROS production in healthy and arthritic rats. Oxygen uptake was increased by MeJA only in livers from treated arthritic rats. This action may bear relation to the increased activity of mitochondrial NADP+-dependent enzymes to provide reducing equivalents for the glutathione cycle. These beneficial effects, however, are associated with a decreased glucose flux through the glycolysis in the liver of arthritic and healthy rats.

Plasma Protein Carbonylation in Haemodialysed Patients: Focus on Diabetes and Gender

Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) experience oxidative/carbonyl stress, which is postulated to increase after the HD session. The influence of diabetes mellitus and sex on oxidation of plasma proteins in ESRD has not yet been clarified despite that diabetic nephropathy is the most common cause of ESRD in developed and developing countries and despite the increasingly emerging differences between males and females in epidemiology, pathophysiology, clinical manifestations, and outcomes for several diseases. Therefore, this study aimed to evaluate the possible effect of type 2 diabetes mellitus, gender, and dialysis filter on plasma level of protein carbonyls (PCO) in ESRD patients at the beginning and at the end of a single HD session. Results show that mean post-HD plasma PCO levels are significantly higher than mean pre-HD plasma PCO levels and that the type of dialysis filter and dialysis technique are unrelated to plasma PCO levels. The mean level of plasma PCO after a HD session increases slightly but significantly in nondiabetic ESRD patients compared to diabetic ones, whereas it increases more markedly in women than in men. These novel findings suggest that women with ESRD are more susceptible than men to oxidative/carbonyl stress induced by HD.

Aging related changes in circulating reactive oxygen species (ROS) and protein carbonyls are indicative of liver oxidative injury.

Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms, plays a major role in inducing oxidative damage and cellular impairment, resulting in a general decline of the physiological functions. The aim of this work was to evaluate age-related changes in circulating ROS levels and plasma protein carbonyls, in very young (2 months aged), young (8 months aged) and in middle age (15 months aged) F344 rats. In addition, the DNA oxidative marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the expression of the DNA repair enzymes APE1, OGG1 and UNG genes were also measured in the liver of these animals. We also determined whether systemic oxidative stress reflects oxidative injury at organ level. Our results demonstrate that the increase in circulating ROS and protein carbonyl content occurs as early as middle age. Moreover, increased 8-OHdG in the liver of 15-month-old rats was at least in part associated with a reduced DNA damage repairing capacity as suggested by the down-regulation of APE1 gene expression. In addition, we demonstrated for the first time, that plasma carbonyls and liver 8-OHdG are well correlated, suggesting that plasma protein carbonyls may be used as a surrogate marker of oxidative injury in target organs.

The effect of resveratrol on glycation and oxidation products in plasma and liver of chronic methylglyoxal-treated rats.

Methylglyoxal (MG) is a highly reactive dicarbonyl compound. It is produced by processes like glycolysis, glucose autooxidation, lipid peroxidation, and protein glycation. It is a major precursor of advanced glycation end products (AGE). It also exacerbates oxidative stress in the organism. Although there are some in vitro studies investigating the effect of resveratrol (RES) as an antioxidant and antiglycating agent on MG-induced toxicity, in vivo effect of RES is unknown. Therefore, we aimed to investigate the efficiency of RES in chronic MG-treated rats. Rats were given incrementally increased doses (100-300 mg/kg) of MG in drinking water for ten weeks. RES (10 mg/kg ip) was administered together with MG. Reactive oxygen species (ROS) formation, thiobarbituric reactive substances (TBARS), protein carbonyl (PC), advanced oxidation protein products (AOPP) and AGE levels as well as ferric reducing antioxidant power (FRAP) values were determined in plasma and liver. Significant increases in plasma TBARS, PC, AOPP and AGE and fructosamine levels were detected in MG-treated rats. However, plasma ROS and FRAP levels remained unchanged. Hepatic ROS, TBARS, PC and AOPP, but not AGE and FRAP levels were also increased in MG-treated rats. RES treatment diminished high levels of plasma PC, AOPP and AGE levels in MG-treated rats. Additionally, significant decreases in hepatic ROS, TBARS, PC and AOPP levels together with histopatological amelioration were detected due to RES treatment in MG-treated rats. Our results indicate that RES may be considered as a protective agent against glycoxidative stress generated by in vivo MG treatment.

The Effects of Magnesium and Zinc Co-Supplementation on Biomarkers of Inflammation and Oxidative Stress, and Gene Expression Related to Inflammation in Polycystic Ovary Syndrome: a Randomized Controlled Clinical Trial.

http://www.irct.ir : IRCT201706075623N121.

Metabolomic Analysis and Antioxidant Effect of Amla (Emblica officinalis) Extract in Preventing Oxidative Stress-Induced Red Cell Damage and Plasma Protein Alterations: An In Vitro Study.

Amla (Emblica officinalis) has antidiabetic, hypolipidemic, anti-inflammatory, and antioxidant properties, but its effect on free radical induced red cell damage and membrane and plasma protein alterations has not been adequately addressed. The aim of the present study was to evaluate the antioxidant property of amla against oxidative stress-induced red cell damage and plasma protein alterations. Red blood cells (RBCs) were preincubated with different concentrations of amla extract (50, 100, 150, and 200 μg/mL) and then treated with physiological (5 mM) and pathological (50 mM) concentrations of glucose for 24 h. In another in vitro study the plasma was pretreated with different concentrations of amla extract and then incubated with 2, 2'-Azo-Bis (2-methylpropionamidine) dihydrochloride (AAPH) for 2 h. After the incubation RBC-malondialdehyde (MDA), RBC-reduced glutathione (GSH), RBC indices, RBC morphometric study, plasma MDA, protein carbonylation, total protein, and albumin were estimated. The antioxidant property of amla was assessed by DPPH assay. RBC-MDA levels were significantly decreased and RBC-GSH levels were significantly increased with higher concentration of amla extract (150 and 200 μg/mL). Red cell count and its indices were improved with the increasing concentration of amla. In addition, at higher concentration, amla restored the RBC membrane integrity. The plasma in vitro study also showed that amla improved the plasma MDA, protein carbonylation, total protein, and albumin levels. Amla extract effectively protected the RBCs and plasma proteins from the reactive oxygen species induced oxidative damage. Liquid chromatography-mass spectrometry (LC-MS) analysis of the extract revealed the presence of gallic acid, quinic acid, and quercetin as the major constituents in addition to the other flavonoids.

Zinc-Induced Metallothionein in Centenarian Offspring From a Large European Population: The MARK-AGE Project.

Metallothionein (MT) family are cysteine-rich proteins that regulate zinc (Zn) homeostasis and protect against oxidative damage. Studies in transgenic mice have shown that MT favorably influence longevity, although their role in human aging is not completely understood. Within the European multicenter study MARK-AGE, we analyzed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2,936 age-stratified subjects (35-75 years) including the general population (RASIG), centenarian offspring (GO), and their spouses (SGO). We found that the lymphocyte capability to induce MT in response to Zn is not affected by aging. However, GO participants showed lower Zn-induced MT and increased basal expression of MT1A, MT1X, and ZnT-1 genes than RASIG subjects. Moreover, Zn-induced MT levels were found to be inversely related with oxidative stress markers (plasma protein carbonyls, 3-nitrotyrosine, and malondialdehyde) in the whole population, but not in GO subjects. In conclusion, our results support the hypothesis that the response to Zn is attenuated in PBMCs of centenarian offspring compared to the general population as a consequence of a tighter control of Zn homeostasis which is likely to provide them constant protection against stress stimuli over the whole lifespan.

Single Silver Nanoparticle Instillation Induced Early and Persisting Moderate Cortical Damage in Rat Kidneys.

The potential toxic effects of silver nanoparticles (AgNPs), administered by a single intratracheal instillation (i.t), was assessed in a rat model using commercial physico-chemical characterized nanosilver. Histopathological changes, overall toxic response and oxidative stress (kidney and plasma protein carbonylation), paralleled by ultrastructural observations (TEM), were evaluated to examine renal responses 7 and 28 days after i.t. application of a low AgNP dose (50 µg/rat), compared to an equivalent dose of ionic silver (7 µg AgNO3/rat). The AgNPs caused moderate renal histopathological and ultrastructural alteration, in a region-specific manner, being the cortex the most affected area. Notably, the bulk AgNO3, caused similar adverse effects with a slightly more marked extent, also triggering apoptotic phenomena. Specifically, 7 days after exposure to both AgNPs and AgNO3, dilatation of the intercapillary and peripheral Bowman’s space was observed, together with glomerular shrinkage. At day 28, these effects still persisted after both treatments, accompanied by an additional injury involving the vascular component of the mesangium, with interstitial micro-hemorrhages. Neither AgNPs nor AgNO3 induced oxidative stress effects in kidneys and plasma, at either time point. The AgNP-induced moderate renal effects indicate that, despite their benefits, novel AgNPs employed in consumer products need exhaustive investigation to ensure public health safety.

Synergistic Effect of Rapamycin and Metformin Against Age-Dependent Oxidative Stress in Rat Erythrocytes.

Erythrocytes are particularly vulnerable toward age-dependent oxidative stress-mediated damage. Caloric restriction mimetics (CRMs) may provide a novel strategy for the maintenance of redox balance as well as effective treatment of age-associated diseases. Herein, we have investigated the beneficial effect of cotreatment with CRM-candidate drugs, rapamycin (an immunosuppressant drug and inhibitor of mammalian target of rapamycin) and metformin (an antidiabetic biguanide and activator of adenosine monophosphate kinase), against aging-induced oxidative stress in erythrocytes and plasma of aging rats. Male Wistar rats of age 4 (young) and 24 months (old) were coexposed to rapamycin (0.5 mg/kg body weight [b.w.]) and metformin (300 mg/kg b.w.), and data were compared with the response of rats receiving an independent exposure to these chemicals at similar doses. The exposure of individual candidate drugs significantly reversed the age-dependent alterations in the endpoints associated with oxidative stress such as reactive oxygen species, ferric reducing ability of plasma, malondialdehyde, reduced glutathione, plasma membrane redox system, plasma protein carbonyl, and acetyl cholinesterase in erythrocytes and plasma of aging rats. However, the cotreatment with rapamycin and metformin showed a significant augmented effect compared with individual drug interventions on reversal of these age-dependent biomarkers of oxidative stress, suggesting a synergistic response. Thus, the findings open up further possibilities for the design of new combinatorial therapies to prevent oxidative stress- and age-associated health problems.

Histopathological evaluation and redox assessment in blood and kidney tissues in a rabbit contrast-induced nephrotoxicity model

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury as a result of iodinated contrast-media use for diagnostic purposes. Pathophysiology remains unclear. In the present study iopromide was administered to New Zealand white rabbits without any prior intervention. Oxidative stress was assessed in blood and tissue level at three anatomical kidney areas (medullary, cortical, juxtamedullary). Histopathological evaluation was also performed. Serum creatinine and urea increased in the CIN groups over 25% at two hours after administration and returned to baseline at 48 h. In kidney tissues, a significant reduction (40%) of catalase in renal cortexes of the CIN groups was observed. Necrosis and tubular vacuolization was also noted that correlated with urea and creatinine levels. Lipid peroxidation decreased at 10 h after administration (>45%) and remained low even at 48 h. Plasma protein carbonyls were significantly increased (67%) in 2 h and dropped later. Serum levels of creatinine and urea at 24 and 48 h significantly correlated with the Total Antioxidant Activity and lipid peroxidation, respectively. Oxidative stress is shown to be involved in CIN development in the rabbit, with more pronounced effects to be confined to the cortex and outer stripe of the outer medulla.

Comparing palm oil tocotrienol rich fraction with α-tocopherol supplementation on oxidative stress in healthy older adults

Vitamin E is a fat-soluble compound and powerful antioxidant that have been shown to protect the cell membranes against damage caused by free radicals. Human vitamin E supplementation studies are usually limited to α-tocopherol but currently tocotrienols are also available. This study aims to compare the effects of tocotrienol rich fraction (TRF) with α-tocopherol (α-TF) supplementation on oxidative stress in healthy male and female older adults aged 50-55 years old. A total of 71 subjects both male and female aged between 50 and 55 years were divided into groups receiving placebo (n=23), α-TF (n=24) and TRF (n=24) for six months. Blood was taken at baseline (month 0), 3 months and 6 months osf supplementation for determination of plasma malondialdehyde (MDA), protein carbonyl, total DNA damage, vitamin D concentration and vitamin E isomers. α-TF supplementation reduced plasma MDA and protein carbonyl in female subjects after 3 and 6 months. TRF supplementation reduced MDA levels in both males and females as early as 3 months while DNA damage was reduced in females only at 6 months. Supplementation with α-TF and TRF increased plasma vitamin D concentration in both males and females after 6 months, but vitamin D concentration in male subjects were significantly higher compared to female subjects in TRF group. Vitamin E isomer determination showed α-TF, α-tocotrienol and γ-tocotrienol were increased in both male and female subjects. In conclusion, TRF supplementation effects were different from α-TF in reducing oxidative stress markers and vitamin D levels with a more pronounced effect in female subjects.

Effect of a 2000-m running test on antioxidant and cytokine response in plasma and circulating cells.

Exercise intensity usually correlates with increased oxidative stress and enhanced cytokine production. However, it is unknown if all types of exercise that induce muscle damage can cause a parallel response in the oxidation balance and cytokine production. To this end, the effect of a 2000-m running test in a group of volunteers that regularly train in aerobic routines was studied. Different circulating parameters were measured, oxidative stress markers (protein carbonyls and malondialdehyde), antioxidant enzyme activity, and cytokine levels in plasma as well as in the main circulating cells of blood samples obtained in basal conditions and after test execution. As a result, the test caused muscle damage evidenced by an increase in circulating creatine kinase and myoglobin. This was accompanied by an increase in protein carbonyls in plasma and peripheral blood mononuclear cells. Activities of antioxidant enzymes (catalase, glutathione peroxidase and reductase, superoxide dismutase) were elevated in peripheral blood mononuclear cells, neutrophils, and erythrocytes after the test. Regarding cytokine production, interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α exhibited no significant changes after the test. Results suggest that this short but intense running exercise (2000m) can induce muscle damage and elicit a good balance between oxidant/antioxidant responses with no changes in the circulating concentration of pro-inflammatory cytokines.