Erythrocyte GSH Levels Research Articles

Effects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis.

N-acetylcysteine (NAC), a thiol-containing antioxidant and glutathione (GSH) precursor, attenuates oxidative stress, and possibly improves psychiatric disorders. This study aimed to evaluate the effects of oral NAC on oxidative stress, depression, and anxiety symptoms in patients with multiple sclerosis (MS). This clinical trial was conducted on 42 MS patients randomly assigned to intervention (n = 21) and control (n = 21) groups. The intervention group received 600 mg of NAC twice daily for 8 weeks, and the control group received a placebo with the same prescription form. An analysis of serum malondialdehyde (MDA), serum nitric oxide (NO), and erythrocyte GSH was carried out on both groups, along with a complete blood count. The Hospital Anxiety and Depression Scale (HADS) was used to assess symptoms of depression (HADS-D) and anxiety (HADS-A). Compared to the control group, NAC consumption significantly decreased serum MDA concentrations (-0.33 [-5.85-2.50] vs. 2.75 [-0.25-5.22] μmol/L; p = 0.03) and HADS-A scores (-1.6 ± 2.67 vs. 0.33 ± 2.83; p = 0.02). No significant changes were observed in serum NO concentrations, erythrocyte GSH levels, and HADS-D scores (p > 0.05). Based on the findings of the present study, NAC supplementation for 8 weeks decreased lipid peroxidation and improved anxiety symptoms in MS patients. The aforementioned results suggest that adjunctive therapy with NAC can be considered an effective strategy for MS management. Further randomized controlled studies are warranted.

Effect of Linseed Oil Supplementation on Lipid Peroxidation and Antioxidant Capacity in Pregnant Overfed Obese Rats and Their Offspring

Effect of Linseed Oil Supplementation on Lipid Peroxidation and Antioxidant Capacity in Pregnant Overfed Obese Rats and Their Offspring

Glutathione Deficiency in HIV-1-Infected Children with Short Stature

Abstract Objective This study was aimed to determine if glutathione (GSH) deficiency occurs in children with HIV infection and whether GSH deficiency is associated with HIV-related short stature. Methods We conducted a cross-sectional study with two age-matched comparison groups in an inner city hospital-based pediatric AIDS/HIV outpatient clinic. Ten perinatally HIV-infected children aged 6 to 49 months with short stature (height–age percentile ≤5) were studied together with age-matched 10 HIV-infected children with normal height and 10 HIV-seronegative children with normal height. Total erythrocyte GSH (GSH and GSH disulfide) levels were determined by a modification of the 5,5′-dithiobis-2-nitrobenzoic acid glutathione disulfide reductase method. Other measures included complete blood counts, lymphocyte subset analysis, plasma albumin, cholesterol, vitamins A and E, and determination of HIV disease stage. Discussion Erythrocyte GSH levels were lower in HIV-infected children with short stature (mean ± standard deviation [SD]: 0.639 µmol/mL ± 0.189) compared with HIV-infected children with normal height (mean ± SD: 0.860 µmol/mL ± 0.358; p < 0.05) and HIV-negative controls (mean ± SD: 0.990 µmol/mL ± 0.343; p < 0.05). Plasma levels of cholesterol, albumin, and vitamins A and E did not differ between the short-stature group and either the HIV-infected normal-height group or HIV-negative controls. Conclusion These results demonstrate a GSH deficiency in HIV-infected children with short stature and support the hypothesis that GSH balance is important in growth among HIV-infected children.

The Effect of Zinc and Melatonin Administration on Lipid Peroxidation, IL-6 Levels, and Element Metabolism in DMBA-Induced Breast Cancer in Rats

The purpose of this study was to investigate the effects of zinc and melatonin administration on interleukin-6, lipid peroxidation parameters, and element metabolism in DMBA-induced breast cancer in female rats. A total of 42 recently weaned Wistar rats were divided into 5 groups as follows: control (group 1), DMBA control (group 2), DMBA + zinc (group 3), DMBA + melatonin (group 4), and DMBA + melatonin and zinc (group 5). Malondialdehyde (MDA) and glutathione (GSH) levels in breast tissue and blood samples were determined via spectrophotometric methods. In addition, iron, magnesium, zinc, and copper levels in serum samples were determined by atomic emission, and plasma interleukin-6 levels were determined by ELISA method. The highest tissue and plasma MDA and the lowest tissue and erythrocyte GSH levels found in the study were in group 2; the highest tissue and erythrocyte GSH levels and the lowest tissue and plasma MDA levels are in group 5 (P < 0.05). Iron, magnesium, and zinc levels of groups 3, 4, and 5 were higher than the DMBA group without administration (group 2), but the copper values were significantly lower (P < 0.05). The highest IL-6 levels were determined in group 2 while IL-6 levels in the DMBA group (G5) treated with combined melatonin and zinc were lower than all other breast cancer groups (P < 0.05). According to the findings obtained in this presented study, combined zinc and melatonin therapy can contribute to the prevention of tumor growth by improving the disruption in element metabolism and suppressing IL-6 levels and reducing tissue damage that causes the cancer.

THE EFFECT OF BETAINE AND PIPERINE ON RATS WITH CREATED ALZHEIMER- LIKE DEMENTIA BY AF64A

OBJECTIVE: The great majority of dementia patients (about 60-70%) suffer from Alzheimer disease (AD). The distinctive pathological signs of AD are senile plaques (SPs), neurofibrillary tangles (NFTS), synaptic loss and neurodegeneration. In this study; it is aimed to determine the damage caused by Acetylcholine Mustard Aziridin Ion (AF64A), which induces neurological anomalies, and the therapeutic effect of antioxidant piperine and betaine.MATERIAL AND METHODS: In this study; 24 Sprague-Dawley male rats were used and 4 groups were formed: Group 1 consisting of healthy rats (control, n = 6); Group 2 (n = 6) with experimental dementia induced by AF64A, group 3 (AF64A betaine, n = 6) treated with betaine and 4 (AF64A piperine, n = 6) treated with piperine. The mRNA levels of mitogen activated protein kinase-1 (MAPK-1) in hippocampus tissue, Malondialdehyde (MDA) levels in liver and blood serum samples and reduced glutathione (GSH) levels in liver and erythrocyte samples were investigated. In addition, behavioral differences were determined in terms of duration using the morris water maze test.RESULTS: The highest GSH levels in liver and erythrocytes were determined in piperine-treated group 4 (p &amp;lt;0.01). The highest results were recorded in group 2 and the lowest results were recorded in group 4 (p &amp;lt;0.05) in terms of liver and plasma MDA levels. The best results in brain tissue pathology findings were also observed in the piperine applied group (p &amp;lt;0.05). There was a significant increase in hippocampus MAPK-1 mRNA levels in group 2 whereas a decrease in group 4.CONCLUSIONS:Determined pathological, biochemical and genetic analyzes beside the longest reaction time in the behavior test result showed that the use of AF64A significantly destroys the brain nerve cell. But especially piperine treatment create almost reversible effect onto AF64A damaging act via bring down all negative signs into control level compare to the betaine effect. AF64A application causes a significant level of brain damage in rats, creating a similar effect to Alzheimer's. As an alternative treatment, it shows that the application of betaine and piperine reduces all the negative consequences of AF64A, especially the application of piperine, to almost completely normal levels. These findings indicate that the use of antioxidant piperine may be beneficial in reducing and/or regressing oxidant effects in dementia and especially in AD.

Oral N-Acetyl Cysteine Administration Improved Oxidative Status in Medical Radiation Workers

Abstract: Medical radiation workers (MRWs) are chronically exposed to low doses of ionizing radiation which has been reported to cause deleterious health effects result from oxidative stress. N-acetyl cysteine (NAC) is the promise choice for treating disorders resulted from excessive production of reactive oxygen species (ROS). The aim of the study was to investigate the role of NAC in protecting medical workers occupationally exposed to low doses of ionizing radiation (IR) via detecting some oxidative stress markers and comparing the results with controls. The studied participants divided into healthy MRWs administered NAC effervescent 600 mg, as a radioprotector (n=50) and healthy non-radiation workers as control group (n=50). Two blood samples were taken from MRWs; before and after taking of NAC and one blood sample from the control group to detect reduced erythrocyte glutathione (GSH), plasma malondialdehyde (MDA) and advanced oxidation protein products (AOPPs). Erythrocyte GSH levels were significantly decreased in MRWs group than control group and significantly increased after oral administration of NAC. Plasma levels of MDA and AOPPs in MRWs group were significantly increased than control group, while their levels were significantly reduced after taking NAC. These findings suggest using of NAC as a promising radioprotector in medical workers occupationally exposed to low dose of IR to reduce the resulted oxidative stress.

Chemopreventive Effect of the Germinated Oat and its Phenolic-AVA Extract in Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) Model of Colon Carcinogenesis in Mice.

The consumption of fruits, vegetables, nuts, legumes, and whole grains has been associated with a lower risk of colorectal cancer (CRC) due to the content of natural compounds with antioxidant and anticancer activities. The oat (Avena sativa L.) is a unique source of avenanthramides (AVAs), among other compounds, with chemopreventive effects. In addition, oat germination has shown enhanced nutraceutical and phytochemical properties. Therefore, our objective was to evaluate the chemopreventive effect of the sprouted oat (SO) and its phenolic-AVA extract (AVA) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mouse model. Turquesa oat seeds were germinated (five days at 25 °C and 60% relative humidity) and, after 16 weeks of administration, animals in the SO- and AVA-treated groups had a significantly lower inflammation grade and tumor (38–50%) and adenocarcinoma (38–63%) incidence compared to those of the AOM+DSS group (80%). Although both treatments normalized colonic GST and NQO1 activities as well as erythrocyte GSH levels, and significantly reduced cecal and colonic β-GA, thus indicating an improvement in the intestinal parameters, the inflammatory states, and the redox states of the animals, SO exerted a superior chemopreventive effect, probably due to the synergistic effects of multiple compounds. Our results indicate that oats retain their biological properties even after the germination process.

Antioxidatant Effect of Atorvastatin and Rosuvastatin in Hyperlipidemic Patients: A Randomized Controlled Trial

Introduction: Hyperlipidemia is a major risk for the development of atherosclerosis leading to cardiovascular complications. Atorvastatin and rosuvastatin are two widely used important members of the HMG-CoA reductase inhibitor (statins). The beneficial effects of statins on clinical events also involve lipid-independent mechanisms which include improvement of oxidative stress status.&#x0D; Objective: To compare the antioxidative effect of atorvastatin and rosuvastatin in patients with hyperlipidemia.&#x0D; Materials and Methods: A prospective randomized single-center analytic study was carried out in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from March 2016 to August 2017 on 52 hyperlipidemic patients. After randomization patients were assigned to atorvastatin 10 mg or rosuvastatin 5 mg daily for 8 weeks. Blood was collected at baseline and after the intervention to measure plasma malondialdehyde (MDA), erythrocyte reduced glutathione (GSH) (as biomarkers of oxidative stress) and serum lipid profile.&#x0D; Results: The baseline characteristics of patients treated with atorvastatin and rosuvastatin were almost identical. The level of plasma MDA in atorvastatin (1.35 ± 0.94 to 0.97± 0.64) and rosuvastatin (1.56±0.69 to 0.98±0.38) group was significantly reduced after intervention (28.15%, p&lt;0.05 and 37.18%, p&lt;0.001 respectively) but no statistically significant difference (p&gt;0.05) was observed between the two statin-treated groups. Erythrocyte GSH level was increased after intervention in both atorvastatin (2.43±2.90 to 4.14 ± 4.87) group (70.37%, p&lt;0.01) and rosuvastatin (2.76±3.80 to 8.36±12.93) group (202.90%, p&lt;0.01), which was statistically significant. No significant difference was observed between the two groups (p&gt;0.05). Both atorvastatin and rosuvastatin significantly improved serum lipid profile.&#x0D; Conclusion: Both atorvastatin and rosuvastatin significantly improved oxidative stress status in hyperlipidemic patients but no significant change was observed between the two statin-treated groups.&#x0D; Journal of Armed Forces Medical College Bangladesh Vol.14(1) 2018: 54-58

The Effects of Hyperbaric Oxygen at Different Pressures on Oxidative Stress and Antioxidant Status in Rats.

Background: The optimal use of oxygen at greater than atmospheric pressures in any operational or therapeutic application (hyperbaric oxygen, HBO2) requires awareness of the fact that the beneficial effects of oxygen coexist with toxic effects depending on the pressure and duration of exposure. In this study, we aimed to investigate the effect of HBO2 therapy on oxidative stress and antioxidant status in commonly used protocol for acute HBO2 indications, such as carbon monoxide intoxication, central retinal artery occlusion, crush injury, gas gangrene, and to compare it with normobaric oxygen (NBO2) in healthy rats. Materials and Methods: Fifty-six male, young adult Wistar albino rats were randomly divided into seven groups and named as Group I through Group VII. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), and erythrocyte glutathione (GSH) levels in control group were compared to the levels in other groups. Results: The increases in MDA levels and the decrease in SOD activities were statistically significant in HBO2 groups at the end of the first 24 h when compared to the control group, and the significant decrease in erythrocyte GSH level was only at 2.4 atmospheres absolute. Conclusions: The present study showed that pressure and frequency of exposure are important factors to consider when investigating HBO2-induced oxidative stress and antioxidant response.

Erythrocyte G6PD activity and GSH level as risk factors for vascular complications among type 2 diabetics in Osogbo, Nigeria

ABSTRACTBackground: Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the oxidation of glucose-6-phosphate (G6P) to produce nicotine-adenosine-dinucleotide phosphate coenzyme (NADPH), a major defense against oxidative damage in erythrocytes. This study aims at evaluating enzymatic G6PD activity and erythrocyte glutathione (eGSH) as a biomarker of vascular complications among type 2 diabetics.Methods: Fasting Plasma glucose (FPG), glycated hemoglobin (HbA1c), erythrocyte G6PD (eG6PD) activity and erythrocyte GSH (eGSH) level were determined along with measured anthropometrics in 120 known type 2 diabetics (comprising 60 diabetics without vascular complications and 60 diabetics with vascular complications) and 50 age and sex matched apparently healthy non diabetes individuals recruited for this study.Results: Result revealed significant reduced eG6PD activity and eGSH levels in type 2 diabetics especially among those with vascular complications as compared to subjects without diabetes, with a slight correlation between eGSH level and eG6PD activity of diabetics with vascular complications.Conclusion: The study, therefore, advocates measurement of G6PD activity and GSH level in type 2 diabetics to properly monitor the progress of the disease.

Oxidative stress and immune aberrancies in attention-deficit/hyperactivity disorder (ADHD): a case-control comparison.

The objective of this study is to compare oxidative stress and immune biomarkers between attention-deficit/hyperactivity disorder (ADHD) patients and controls without ADHD. A case-control comparison between 57 paediatric (6-12years) untreated ADHD patients from the Antwerp University Hospital and 69 controls without ADHD from random schools in Flanders, Belgium, was conducted. Erythrocyte glutathione (GSH) and plasma lipid-soluble antioxidants (retinol, α-tocopherol, γ-tocopherol, retinyl palmitate, β-carotene, and co-enzyme Q10) were determined by HPLC with electrochemical detection, plasma malondialdehyde (MDA) by HPLC with fluorescence detection, plasma cytokines (interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor (TNF) and interferon (INF)-γ) and immunoglobulins (IgE, IgG and IgM) by flow cytometry and urinary 8-hydroxy-2'deoxyguanosine (8-OHdG) levels by ELISA assay. Dietary habits were determined by a food frequency questionnaire. Plasma MDA levels were on average 0.031µM higher in patients than in controls (p < 0.05), and a trend for higher urinary 8-OHdG was observed. Erythrocyte GSH and plasma retinyl palmitate levels, as well as IgG and IgE levels, were higher in patients than in controls as well (on average 93.707µg/ml, 0.006µg/ml, 301.555µg/ml and 125.004µg/ml, resp., p < 0.05). Finally, a trend for lower plasma IL-5 levels was observed. After Bonferroni correction for multiple testing, the difference in GSH levels remained statistically significant (nominally significant for retinyl palmitate), while significance was lost for MDA, IgG and IgE levels. Dietary habits do not appear to cause the observed differences. These results point at the potential involvement of slight oxidative stress and immune disturbances in ADHD.

Effect of Zinc and Melatonin on Oxidative Stress and Serum Inhibin-B Levels in a Rat Testicular Torsion–Detorsion Model

The present study was aimed to examine the effects of 3-week zinc and melatonin administration on testicular tissue injury and serum Inhibin-B levels caused by unilateral testicular torsion-detorsion in rats. The study was performed on 60 Wistar Albino-type adult male rats. The animals were allocated to 6 groups in equal numbers. 1. Control; 2. Sham; 3. Ischemia-reperfusion; 4. Zinc+ischemia-reperfusion; 5. Melatonin+ischemia-reperfusion; 6. Zinc+melatonin+ischemia-reperfusion. Zinc and melatonin were administered before ischemia-reperfusion at doses of 5 and 3mg/kg respectively, by intraperitoneal route for a period of 3weeks. Testicular torsion-detorsion procedures consisted of ischemia for 1h and then reperfusion for another hour of the left testis. Blood and testicular tissue samples were collected to analyze erythrocyte and tissue GSH and plasma and tissue MDA, Inhibin-B levels. The highest erythrocyte and testis GSH values were found in zinc, melatonin, and zinc+melatonin groups (p<0.001). Torsion-detorsion group has significantly lower erythrocyte GSH levels and higher plasma MDA values (p<0.001). Serum inhibin-B and spermatogenic activity levels in the torsion-detorsion group were also significantly lower than those in the other groups (p<0.001). However, zinc-, melatonin-, and melatonin+zinc-supplemented groups have higher inhibin-B and spermatogenetic activity (p<0.001). The results of the study show that zinc, melatonin, and melatonin+zinc administration partially restores the increased oxidative stress, as well as the reduced inhibin-B and spermatogenic activity levels in testes ischemia-reperfusion in rats. Suppressed inhibin-B levels in the testicular tissue may be a marker of oxidative stress.

Level of Glutathione After Administration of Provitamin B5 to Plasmodium berghei Infected BALB/c Mice

Introduction: Malaria was one of the health problem in developing country including Indonesia. Three hundred to five hundred million people suffered from malaria, and causing more than one million death annually. The objective of this study was to find out erythrocyte GSH level and compared to parasitemiapercentage due to provitamin B5 administration to Plasmodium berghei infected BALB/c mice.&#x0D; Method: 32 males BALB/c mice were infected by 200 µL blood which contain 106 Plasmodium berghei intraperitoneally. Then, samples were separated randomly into four groups, namely control group, group P1, group P2 and group P3. As soon as parasitemia reached 1 – 5 % the treatment should begin. Control group was administered aquades by gavage, group P1 administered 0.14 g/kgBW provitamin B5, group P2 administered 1.4 g/kgBW provitamin B5, group P3 administered 2.8 g/kgBW provitamin B5, all were treated by gavage. Provitamin B5 treatment followed the protocol in the 4-days suppressive test of blood schizontocidal action. On the fourth day the mice were terminated and blood samples from intracardiac was taken. Thus, blood samples conducted erythrocyte GSH measurement using Anderson method.&#x0D; Result: The results were analysed by using Anova α = 0.05, and continued by LSD if the result showed a significant difference. Erythrocyte GSH level decreased in all groups. Erythrocyte GSH in group P3 increased significant compared to group P1 ( P&lt;0.05). Parasitemia measurement using Percent method showed a significant decrease in group P1 ( 48 % ) and in group P2 ( 62 % ) (P&lt;0.05), while in group P3 no significant difference from control group.&#x0D; Conclusion: Erythrocyte GSH level decreased in administration of Provitamin B5 by increasing dosage, in contrast to parasitemia percentage.

Low Retinal Dehydrogenase 1 (RALDH1) Level in Prepubertal Boys with Autism Spectrum Disorder: A Possible Link to Dopamine Dysfunction?

ObjectiveRetinal dehydrogenase 1 (RALDH1) is a cytosolic enzyme which acts both as a source of retinoic acid (RA) and as a detoxification enzyme. RALDH1 has key functions in the midbrain dopaminergic system, which influences motivation, cognition, and social behavior. Since dopamine has been increasingly linked to autism spectrum disorder (ASD), we asked whether RALDH1 could contribute to the autistic phenotype. Therefore, we investigated for the first time the levels of RALDH1 in autistic patients. To further assess the detoxification function of RALDH1, we also explored 4-hydroxynonenal protein adducts (4-HNE PAs) and reduced glutathione (GSH) levels. Moreover, considering the effect of testosterone on RALDH1 expression, we measured the second to fourth digit ratio (2D:4D ratio) for both hands, which reflects exposure to prenatal testosterone.MethodsMale patients with ASD (n=18; age, 62.9±4.3 months) and healthy controls (n=13; age, 78.1±4.9 months) were examined. Erythrocyte RALDH1, serum 4-HNE PAs and erythrocyte GSH levels were measured using colorimetric assays, and digit lengths were measured using digital calipers.ResultsWe found significantly lower (−42.9%) RALDH1 levels in autistic patients as compared to controls (p=0.032). However, there was no difference in 4-HNE PAs levels (p=0.368), GSH levels (p=0.586), or 2D:4D ratios (p=0.246 in the left hand, p=0.584 in the right hand) between healthy controls and autistic subjects.ConclusionWe concluded that a subset of autistic patients had a low RALDH1 level. These results suggest that low RALDH1 levels could contribute to the autistic phenotype by reflecting a dopaminergic dysfunction.

Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function.

Glutathione (GSH) is the most abundant endogenous antioxidant and a critical regulator of oxidative stress. Maintenance of optimal tissues for GSH levels may be an important strategy for the prevention of oxidative stress-related diseases. We investigated if oral administration of liposomal GSH is effective at enhancing GSH levels in vivo. A 1-month pilot clinical study of oral liposomal GSH administration at two doses (500 and 1000 mg of GSH per day) was conducted in healthy adults. GSH levels in whole blood, erythrocytes, plasma and peripheral blood mononuclear cells (PBMCs) were assessed in 12 subjects at the baseline and after 1, 2 and 4 weeks of GSH administration. GSH levels were elevated after 1 week with maximum increases of 40% in whole blood, 25% in erythrocytes, 28% in plasma and 100% in PBMCs occurring after 2 weeks (P<0.05). GSH increases were accompanied by reductions in oxidative stress biomarkers, including decreases of 35% in plasma 8-isoprostane and 20% in oxidized:reduced GSH ratios (P<0.05). Enhancements in immune function markers were observed with liposomal GSH administration including Natural killer (NK) cell cytotoxicity, which was elevated by up to 400% by 2 weeks (P<0.05), and lymphocyte proliferation, which was elevated by up to 60% after 2 weeks (P<0.05). Overall, there were no differences observed between dose groups, but statistical power was limited due to the small sample size in this study. Collectively, these preliminary findings support the effectiveness of daily liposomal GSH administration at elevating stores of GSH and impacting the immune function and levels of oxidative stress.

Erythrocyte glutathione levels as long-term predictor of transition to psychosis

A high proportion of individuals deemed at elevated risk for psychosis will actually never progress to develop the illness. Pharmaceutical intervention may not be necessary in these cases, and may in fact be damaging depending on the invasiveness of the treatment strategy. This highlights the need for biomarkers that are better able to reliably differentiate between at-risk individuals who will subsequently transition to psychosis and those who will not. Low glutathione (GSH) levels have been observed in schizophrenia and in patients with first-episode psychosis. The aim of this study was to determine the predictive value of erythrocyte GSH levels on the transition to psychosis in individuals at risk of developing the illness. Erythrocyte GSH levels were measured in 36 at-risk individuals, 15 of whom had transitioned to psychosis at the 7-year follow-up. Univariate Cox regression analysis showed that transition to psychosis at the 7-year time point was significantly associated with low GSH levels at baseline. The area under the receiving operating characteristic curve was 0.819, indicating that GSH can be considered a good predictor of outcome. Although these results need to be replicated, adding the criterion ‘low erythrocyte GSH’ to the set of criteria used to identify individuals at risk of psychosis may be indicated.

Comparative Study of Protective Effect of Tomato Juice and N-Hexane Extract of Tomato on Blood Lipids and Oxidative Stress in Cholesterol-Fed Rats

Background: Hyperlipidemia is a well-established risk factor in pathogenesis of atherosclerosis and atherosclerosisassociated conditions by enhancing oxidative stress. Dietary supplementation of tomato which is enriched with antioxidants especially like lycopene may therefore be effective in reducing oxidative stress during hyperlipidemic condition. The study evaluates and compares the protective effect of tomato juice and n-Hexane extract of tomato on oxidative stress in hyperlipidemic rats.Methodology: This experimental study was carried out among 42 rats divided in 7 groups. Rats were treated with 0.5% cholesterol (suspension of cholesterol powder in soybean oil) at a dose of 50 mg/ ml once daily through intragastric tube for 8 weeks. In other two groups of rats tomato juice (1 mg/kg) or n-Hexane extract of tomato (1 mg/kg) with 0.5% cholesterol were given orally once daily through intragastric tube for 8 weeks. Serum lipid profile, body weight, plasma malondialdehide (MDA) and erythrocyte reduced glutathione(GSH) levels were measured after 8 weeks in all the groups.Results: Administration of cholesterol caused significant increase (p&lt;0.001) in serum cholesterol, serum triglyceride (TG), serum low-density lipoprotien cholesterol (LDL-C)and significant decrease (p&lt;0.001) in serum high-density lipoprotein cholesterol (HDL-C) which were associated with significant increment (p&lt;0.001) in plasma MDA levels and depletion(p&lt;0.001) in erythrocyte GSH levels. Concomitant treatment of tomato juice or n-Hexane extract of tomato with cholesterol reduced (p&lt;0.001) serum cholesterol, serum LDL-C, body weight and increased serum HDL-C level in cholesterol plus tomato juice treated group (p&lt;0.001) and in cholesterol plus n-Hexane extract of tomato treated group (p&lt;0.05).But serum triglyceride was decreased(p&lt;.05) only in cholesterol plus tomato juice treated group. Simultaneous treatment of tomato juice or n-Hexane extract of tomato with cholesterol decreased (p&lt;0.001) plasma MDA level and increased (p&lt;0.001) erythrocyte GSH level. However, significant differences were noted between the effect of tomato juice and n-Hexane extract of tomato on serum cholesterol (p&lt;0.001), serum triglyceride (p&lt;.05), serum LDL-C (p&lt;0.001), serum HDL-C level(p&lt;0.01) and plasma MDA(p&lt;0.001) and erythrocyte GSH (p&lt;0.001) levels. But no significant difference was noted on body weight.Conclusion: It may be concluded that both tomato juice and n-Hexane extract of tomato offered protection against hyperlipidemia and oxidative stress, but the protection afforded by tomato juice was superior to n-Hexane extract of tomato.Anwer Khan Modern Medical College Journal Vol. 8, No. 1: Jan 2017, P 30-37

Pharmacometabolomics for Predicting Variable Busulfan Exposure in Pediatric HSCT Patients

Optimal dosing for busulfan is important for minimization of systemic toxicity from overexposure and graft failure or relapse from underexposure. Herein, we investigated potential markers for predicting individual variation in the pharmacokinetics of busulfan, and suggested possible mechanism for inter-individual variability by using pharmacometabolomics.Fifty-nine pediatric patients undergoing busulfan-based conditioning chemotherapy for hematopoietic stem cell transplantation were divided into three groups according to the area under the concentration-time curve (AUC) of busulfan; low-, medium-, and high-AUC group. Nontargeted metabolic profiling of baseline urine samples showed that deferoxamine metabolites were abundant, while 2 acylcarnitines and phenylacetylglutamine were significantly lower in high-AUC group, compared with low-AUC group. Higher level of deferoxamine, an iron-chelating agent for the patients with a high serum ferritin level during the conditioning chemotherapy, suggested pharmacokinetic interaction between serum ferritin level and busulfan exposure. Retrospective analysis of the correlation between serum ferritin level and busulfan AUC showed positive correlation in 130 pediatric patients. The optimal busulfan dose to meet the target AUC of 18,750 μg*h/L/day was calculated to be 119.7 ± 30.1 mg/m2 in patients with ferritin < 1,000 ng/mL and 106.1 ± 29.3 mg/m2in patients with ferritin ≥ 1,000 ng/mL (P=0.021).Mechanismly, previous studies have indicated that ferritin, acylcarnitine and phenylacetylglutamine are closely associated with liver function. Increased serum ferritin is thought to be responsible for an increased production of oxygen free radicals and activation of GSH turnover, which means reduction of GSH levels in both plasma and erythrocytes and this depletion seems to be related to the decrease of busulfan metabolism. Down regulation of acylcarnitines is associated with deregulation of mitochondrial fatty acid β-oxidation by hepatic injury. PAGN, a marker of waste nitrogen scavenger, was down-regulated which indicates ammonia-related metabolism could also be involved in busulfan exposure. Hyperammonemia, a clinical condition of elevated ammonia levels, is mainly lead by liver cell damage.Taken together, our findings demonstrate that elevated serum ferritin levels are a potential biomarker correlated with busulfan exposure and provide some evidence that busulfan metabolism seems to decrease in the patients with reduced liver function. DisclosuresNo relevant conflicts of interest to declare.

Effect of Copper on l-Cysteine/l-Cystine Influx in Normal Human Erythrocytes and Erythrocytes of Wilson's Disease.

Wilson's disease is a disease of abnormal copper metabolism in which free serum copper level is raised. The objective of the study was to determine, whether in Wilson disease, l-cysteine/l-cystine influx into RBC was decreased or not and the specific amino acid transporter affected by copper in normal human RBC. For l-cysteine/l-cystine influx, ten untreated cases, ten treated cases and ten age and sex matched healthy controls were recruited. To study the effect of copper on l-cysteine/l-cystine influx in RBC, 15 healthy subjects were selected. RBC GSH and l-cysteine/l-cystine influx were estimated by Beautler's and Yildiz's method respectively. In untreated cases, l-cysteine/l-cystine influx and erythrocyte GSH level were decreased showing that elevated level of free copper in serum or media decreased l-cysteine/l-cystine influx in human RBC. Copper treatment inhibited L amino acid transporter in normal RBC specifically.

The antioxidant N-Acetylcysteine does not improve glucose tolerance or β-cell function in type 2 diabetes

Hyperglycemia induces oxidative stress and thereby may exacerbate β-cell dysfunction in type 2 diabetes (T2DM). Notably, glutathione (GSH), synthesized from N-Acetylcysteine (NAC), neutralizes reactive oxygen species within cells and is low in individuals with diabetes. AimDetermine if NAC supplementation improves β-cell function and glucose tolerance by decreasing oxidative stress in T2DM. MethodsThirteen subjects (6M/7F) with T2DM (duration: 0–13 years, median: 2years), treated with diet/exercise alone (n=7) or metformin (n=6), underwent a 2-h oral glucose tolerance test (OGTT) at baseline, after 2weeks supplementation with 600mg NAC orally twice daily, and again after 2weeks supplementation with 1200mg NAC twice daily. The following measurements were made: fasting glucose and fructosamine for glycemic control, incremental AUC glucose (0–120min) for glucose tolerance, and Δ insulin/Δ glucose (0–30min) for the early insulin response to glucose. Fasting erythrocyte GSH and GSSG (oxidized glutathione) levels, plasma thiobarbituric acid reactive substances (TBARS), and urine F2α isoprostanes were measured to assess oxidative status. ResultsSubjects were middle aged (mean±SEM: 53.9±3.2years), obese (BMI 37.3±2.8kg/m2), and relatively well-controlled (HbA1c 6.7±0.3%, 50mmol/mol). Glycemic control, glucose tolerance, insulin release, and oxidative markers did not change with either dose of NAC. ConclusionsBased on the lack of any short-term benefit from NAC supplementation on markers of glucose metabolism, β-cell response, and oxidative status, it is unlikely to be a valuable therapeutic approach for treatment of type 2 diabetes.