Identification of HGD and GSTZ1 as Biomarkers Involved Metabolic Reprogramming in Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of renal cell carcinoma, accounting for more than 80% of patients. Most patients are diagnosed at an advanced stage due to being asymptomatic early on. Advanced KIRC has an extremely poor prognosis due to its inherent resistance to radiotherapy and chemotherapy. Therefore, a comprehensive understanding of the molecular mechanisms of KIRC and the development of effective early diagnostic and therapeutic strategies is urgently needed. In this study, we aimed to identify the prognosis-related biomarker and analyzed its relationship with tumor progression. Metabolic changes are an important feature of kidney cancer, where the reduction of fumarate allows us to target the tyrosine metabolic pathway. The homogentisate 1,2-dioxygenase (HGD) and glutathione S-transferase zeta 1 (GSTZ1) related with prognosis of KIRC was identified through bioinformatics analysis based on The Cancer Genome Atlas (TCGA) databases. Mechanistically, we found that decreased HGD and GSTZ1 promote aerobic glycolysis in KIRC, coordinate the balance of amino acid metabolism and energy metabolism in tumor cells, and ultimately activate the tumor cell cycle and tumor progression. In summary, we identified the tyrosine metabolizing enzymes HGD and GSTZ1 as biomarkers of KIRC, which will further the understanding of the tumor metabolism profile, provide novel strategies and theoretical support for diagnosing and treating KIRC and as referential for future clinical research.

Chromatin accessibility analysis identifies GSTM1 as a prognostic marker in human glioblastoma patients.

BACKGROUND: Glioblastoma (GBM) is a malignant human brain tumor that has an extremely poor prognosis. Classic mutations such as IDH (isocitrate dehydrogenase) mutations, EGFR (epidermal growth factor receptor) alternations, and MGMT (O6-methylguanine-methyltransferase) promoter hypermethylation have been used to stratify patients and provide prognostic significance. Epigenetic perturbations have been demonstrated in glioblastoma tumorigenesis. Despite the genetic markers used in the management of glioblastoma patients, new biomarkers that could predict patient survival independent of known biomarkers remain to be identified. METHODS: ATAC-seq (assay for transposase accessible chromatin followed by sequencing) and RNA-seq have been used to profile chromatin accessible regions using glioblastoma patient samples with short-survival versus long-survival. Cell viability, cell cycle, and Western blot analysis were used to characterize the cellular phenotypes and identify signaling pathways. RESULTS: Analysis of chromatin accessibility by ATAC-seq coupled with RNA-seq methods identified the GSTM1 (glutathione S-transferase mu-1) gene, which featured higher chromatin accessibility in GBM tumors with short survival. GSTM1 was confirmed to be a significant prognostic marker to predict survival using a different GBM patient cohort. Knockdown of GSTM1 decreased cell viability, caused cell cycle arrest, and decreased the phosphorylation levels of the NF-kB (nuclear factor kappa B) p65 subunit and STAT3 (signal transducer and activator of transcription 3) (pSer727). CONCLUSIONS: This report demonstrates the use of ATAC-seq coupled with RNA-seq to identify GSTM1 as a prognostic marker of GBM patient survival. Activation of phosphorylation levels of NF-kB p65 and STAT3 (pSer727) by GSTM1 is shown. Analysis of chromatin accessibility in patient samples could generate an independent biomarker that can be used to predict patient survival.

Modulation of Renal Function in a Metabolic Syndrome Rat Model by Antioxidants in Hibiscus sabdariffa L.

Metabolic syndrome (MS) is the association of three or more pathologies among which obesity, hypertension, insulin resistance, dyslipidemia, and diabetes are included. It causes oxidative stress (OS) and renal dysfunction. Hibiscus sabdariffa L. (HSL) is a source of natural antioxidants that may control the renal damage caused by the MS. The objective of this work was to evaluate the effect of a 2% HSL infusion on renal function in a MS rat model induced by the administration of 30% sucrose in drinking water. 24 male Wistar rats were divided into 3 groups: Control rats, MS rats and MS + HSL rats. MS rats had increased body weight, systolic blood pressure, triglycerides, insulin, HOMA index, and leptin (p ≤ 0.04). Renal function was impaired by an increase in perfusion pressure in the isolated and perfused kidney, albuminuria (p ≤ 0.03), and by a decrease in clearance of creatinine (p ≤ 0.04). The activity of some antioxidant enzymes including the superoxide dismutase isoforms, peroxidases, glutathione peroxidase, glutathione-S-transferase was decreased (p ≤ 0.05). Lipoperoxidation and carbonylation were increased (p ≤ 0.001). The nitrates/nitrites ratio, total antioxidant capacity, glutathione levels and vitamin C were decreased (p ≤ 0.03). The treatment with 2% HSL reversed these alterations. The results suggest that the treatment with 2% HSL infusion protects renal function through its natural antioxidants which favor an improved renal vascular response. The infusion contributes to the increase in the glomerular filtration rate, by promoting an increase in the enzymatic and non-enzymatic antioxidant systems leading to a decrease in OS and reestablishing the normal renal function.

Netrin-1 and clusterin: Innovative potential diagnostic biomarkers for early renal damage in ß-thalassemia major children.

BACKGROUND: Children with ß-thalassemia major (ß-TM) suffer from tubular dysfunction even before the onset of any renal impairment symptoms and/or clinical signs. Therefore, identifying innovative biomarkers allowing early renal damage detection has focused attention. AIM: This study aims to preliminary assess Netrin-1(NTN-1) and clusterin (CLU) in ß-TM children and explore their possible roles as surrogate noninvasive biomarkers of renal tubular dysfunction. SUBJECTS AND METHODS: In this study, 40 ß-TM children and 30 healthy children were enrolled. Routine serum and urinary biochemical variables were determined. Urinary NTN-1 and CLU levels were measured using ELISA and their mRNA expression in PBMCs were assayed using real-time PCR. Serum TNF-α, MDA levels and GST activity were measured. RESULTS: Urinary NTN-1 and CLU concentrations and mRNA relative expression levels in PBMCs were significantly increased in ß-TM children relative to controls. Oxidative stress and inflammatory markers revealed significant elevation in ß-TM children compared to controls. The change in these parameters correlated significantly with other renal parameters. ROC curves analysis showed that urinary NTN-1 and CLU levels are of promising diagnostic performance. CONCLUSION: Our results suggest that NTN-1 and CLU are qualified as new noninvasive biomarker panels for early detection of renal injury in ß-TM children. Moreover, urinary NTN-1 is recommended as a precise one during the clinical practices.

Plasma redox and inflammatory patterns during major depressive episodes: a cross-sectional investigation in elderly patients with mood disorders.

BACKGROUND: While both depression and aging have been associated with oxidative stress and impaired immune response, little is known about redox patterns in elderly depressed subjects. This study investigates the relationship between redox/inflammatory patterns and depression in a sample of elderly adults. METHODS: The plasma levels of the advanced products of protein oxidation (AOPP), catalase (CAT), ferric reducing antioxidant power (FRAP), glutathione transferase (GST), interleukin 6 (IL-6), superoxide dismutase (SOD), total thiols (TT), and uric acid (UA) were evaluated in 30 patients with mood disorders with a current depressive episode (depressed patients, DP) as well as in 30 healthy controls (HC) aged 65 years and over. Subjects were assessed with the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Geriatric Depression Rating Scale (GDS), the Scale for Suicide Ideation (SSI), the Reason for Living Inventory (RFL), the Activities of Daily Living (ADL), and the Instrumental Activity of Daily Living (IADL). RESULTS: DP showed higher levels than HC of AOPP and IL-6, while displaying lower levels of FRAP, TT, and CAT. In the DP group, specific correlations were found among biochemical parameters. SOD, FRAP, UA, and TT levels were also significantly related to psychometric scale scores. CONCLUSION: Specific alterations of redox systems are detectable among elderly DP.

Toxicity and biomarkers of micro-plastic in aquatic environment: a review.

Microplastics (MPs; <5 mm) are found in all aquatic environments. Due to harmful impacts, MPs pose a great threat to the aquatic ecology. Therefore, this review aims to provide an overview of the risk, bioavailability, and toxicity of MPs in aquatic organisms. Various factors affecting MPs bioavailability and level of risks at cellular and molecular level on aquatic organisms are comprehensively discussed. More specifically biomarkers for antioxidant response (superoxide dismutase, catalase, glutathione peroxidase, reductase, and glutathione S-transferase), neurotoxic impairment (acetylcholinesterase), lysosomal activity alteration, and genotoxicity have been discussed in detail. Biomarkers are powerful tool in the monitoring programme, but the collection of literature on biomarkers for MPs is limited. Thus, here we demonstrate how to evaluate MPs impact, in monitoring programme, on organisms using biomarkers in aquatic environment. This review would broaden the existing knowledge on the toxic effect and biomarkers of MPs and offer research priorities for future studies.

Nondestructive biomarkers in giant toad (Rhinella marina) to assess the effect of complex mixture of pollutants in Coatzacoalcos River, Mexico.

In this study, we evaluated the usefulness of nondestructive biomarkers approach in giant toads (Rhinella marina). We obtained blood samples and the residual condition index of toads from rural and industrial zones from Coatzacoalcos River, Mexico (COA). In the blood samples, we determined the activity of enzymes, lipid peroxidation, and the presence of cell death (apoptosis). We found that the activity of the enzyme delta-aminolevulinic dehydratase was lower. Still, the glutathione s-transferase activity and the percentage of apoptosis in erythrocytes were higher in the toads of COA than laboratory toads. Meanwhile, some biomarkers in toads showed differences when compared between Industrial and Rural zones. These results and correlations between biomarkers showed how the response changed in the toads living near the industrial zones. We demonstrate that a nondestructive biomarkers approach can be useful in environmental studies with anuran amphibians.

The blood and mRNA levels of antioxidant-related factors in common carp (Cyprinus carpio) fed p-Coumaric acid.

The natural antioxidants are well known for their antioxidative activity without side effects when compared to antibiotics. Hence, the present study aimed at evaluating p-Coumaric acid as an antioxidant additive on the blood and mRNA levels of antioxidant-related factors in common carp (Cyprinus carpio). Fish fed the basal diet supplemented with p-Coumaric at 0, 0.5, 1, and 1.5 g/kg for 56 days, then the serum, intestine, and liver samples were collected. The growth performance of fish fed with CA showed significantly (P < 0.05) improved FW, WG, and SGR compared to those of the control one. However, the feed conversion ratio was significantly (P < 0.05) reduced in fish fed 1 and 1.5 g/kg diet levels. SOD was not significantly differed among the groups fed with varied p-Coumaric acid (P > 0.05). Serum GPX and TAC were enhanced considerably by p-Coumaric acid regarding the control with the highest being in fish fed 1.5 g/kg diet (P < 0.05). Serum CAT was more elevated in fish provided p-Coumaric acid at 1 or 1.5 g/kg than the control while fish fed 0.5 g/kg did not display significant changes. MDA level significantly decreased by all p-Coumaric acid groups compared to the control one, and the lowest level was observed in 1.5 g/kg (P < 0.05). The mRNA level of CAT was significantly upregulated in the liver by p-Coumaric acid at 1 or 1.5 g/kg (P < 0.05), while the intestine CAT did not influence by p-Coumaric acid (P > 0.05). The measured SOD in the liver and intestine samples revealed no changes in common carp fed p-Coumaric acid (P > 0.05). GPX was significantly upregulated in the intestine by p-Coumaric acid at 1 or 1.5 g/kg (P < 0.05), whereas the liver GPX was upregulated by p-Coumaric acid at 1.5 g/kg. The mRNA level of the GST gene in the intestine of common carp was upregulated by p-Coumaric acid at 1.5 g/kg, whereas the liver displayed upregulated GST in fish fed 1 g/kg diet. The present study approved the application of p-Coumaric acid as a natural antioxidant for friendly, sustainable aquaculture.

Vitamin C Deficiency and the Risk of Osteoporosis in Patients with an Inflammatory Bowel Disease.

Recent research studies have shown that vitamin C (ascorbic acid) may affect bone mineral density and that a deficiency of ascorbic acid leads to the development of osteoporosis. Patients suffering from an inflammatory bowel disease are at a risk of low bone mineral density. It is vital to notice that patients with Crohn's disease and ulcerative colitis also are at risk of vitamin C deficiency which is due to factors such as reduced consumption of fresh vegetables and fruits, i.e., the main sources of ascorbic acid. Additionally, some patients follow diets which may provide an insufficient amount of vitamin C. Moreover, serum vitamin C level also is dependent on genetic factors, such as SLC23A1 and SLC23A2 genes, encoding sodium-dependent vitamin C transporters and GSTM1, GSTP1 and GSTT1 genes which encode glutathione S-transferases. Furthermore, ascorbic acid may modify the composition of gut microbiota which plays a role in the pathogenesis of an inflammatory bowel disease.

In vivo assessment of the protection conferred by beta-glucans from Pleurotus ostreatus against the harmful effects of acrylamide intake (Part I) / Evaluación in vivo de la protección que confieren los beta-glucanos de Pleurotus ostreatus frente a los efectos nocivos de la ingestión de acrilamida (Parte I)

INTRODUCTION: acrylamide is formed in food through Maillard's reaction during thermal processing, and has been shown to be neurotoxic in humans, and a possible carcinogen. Studies have shown that β-glucans from Pleurotus ostreatus have diverse biological properties such as antioxidant and anticancer activities. OBJECTIVE: the aim of this work was to evaluate the protective effect of β-glucans from Pleurotus ostreatus against the harmful effects of acrylamide consumption in mice. METHODS: β-glucans were obtained by alkaline-acid hydrolysis of Pleurotus ostreatus, and the content was characterized by liquid chromatography. To evaluate the effect of β-glucans on the expression of glutathione, Balb/c mice were used, and 4 test groups were established. All groups were fed normally, and the groups treated with acrylamide were administered the compound intragastrically at a concentration of 50 μg/mL; β-glucans were administered at a concentration of 50 μg/mL. RESULTS: mice exposed to acrylamide showed a marked variation in the activity of glutathione enzymes in the liver. Significant differences (p < 0.05) were only found in the expression of glutathione transferase, which was increased almost 3 times in the group treated with β-glucans as compared with the control group, and 1.5 times as compared with the group treated with acrylamide. CONCLUSIONS: the results show that β-glucans could act by increasing the activity of enzymes involved in xenobiotic detoxification, thus protecting the biological system against the harmful effects caused by acrylamide intake

INTRODUCCIÓN: la acrilamida se forma en los alimentos a través de la reacción de Maillard durante el proceso térmico, y ha demostrado ser neurotóxica en humanos y un posible carcinógeno. Algunos estudios han demostrado que los β-glucanos de Pleurotus ostreatus tienen diversas propiedades biológicas, como actividades antioxidantes y anticancerígenas. OBJETIVO: el objetivo de este trabajo fue evaluar el efecto protector de los β-glucanos de Pleurotus ostreatus contra los efectos nocivos por consumo de acrilamida en ratones (prueba in vivo). MÉTODOS: los β-glucanos se obtuvieron por hidrólisis ácido-alcalina de Pleurotus ostreatus y su contenido se caracterizó por cromatografía líquida. La oxidación de los lípidos se evaluó mediante el método de TBARS, y para evaluar el efecto de los β-glucanos en la expresión de glutatión se usaron ratones Balb/c, y se establecieron 4 grupos de prueba. Todos los grupos fueron alimentados normalmente; a lo grupos tratados con acrilamida, esta se les administró intragástricamente en una concentración de 50 μg/ml, y los β-glucanos en una concentración de 50 μg/ml. RESULTADOS: en el presente trabajo, los ratones expuestos a acrilamida mostraron una marcada variación en la actividad de las enzimas de glutatión determinadas en el hígado. Solo se encontraron diferencias significativas (p < 0,05) en la expresión de glutatión-transferasa, que aumentó casi 3 veces en el grupo tratado con β-glucano en comparación con el grupo de control, y 1,5 veces con respecto al grupo tratado con acrilamida. CONCLUSIONES: los resultados muestran que los β-glucanos podrían actuar como agentes antioxidantes que protegen el hígado contra el estrés oxidativo causado por la ingesta de acrilamida

DNA damage analysis concerning GSTM1 and GSTT1 gene polymorphism in gold jewellery workers from Peshawar Pakistan.

PURPOSE: To evaluate the genotoxic effects of gold jewellery fumes and its association with GSTM1 and GSTT1 genetic polymorphisms. MATERIALS AND METHODS: We examined 94 subjects including 54 gold jewellery workers and 40 controls. The DNA damage was evaluated by alkaline comet assay and genotyping by PCR. RESULTS: The mean total comet score (TCS) in gold jewellery workers was significantly higher as compared to the control subjects (128.0 ± 60.6 versus 47.7 ± 21.4; p = 0.0001). Duration of occupational exposure had positive correlation (r = 0.453, p < 0.01) with DNA damage. Age and tobacco use had significant effects on the TCS of the exposed group as compared to the control group (p < 0.05). The frequency of the GSTM1-null genotype in the exposed group was significant (p = 0.004) as compared to the control group. No significant association (p > 0.05) between the GSTM1 and GSTT1 genotypes and DNA damage was found. CONCLUSIONS: Our results suggest that there is increased DNA damage in gold jewellery workers due to their occupational surroundings. Hence there is a strong need to educate the workers about the adverse health effects of potentially hazardous chemicals and highlight the importance of using protective measures.

Exposure to organic solvents and hepatotoxicity.

The purpose of this study was to identify the long-term effect of chemical exposure on the liver. Laboratory tests included alanine aminotransferase (ALT) dosage and oxidative stress tests, such as thiobarbituric acid reactive substances in plasma and superoxide dismutase (SOD) and glutathione S-transferase analysis in erythrocytes. The cross-sectional study comprised 70 workers, 30 of them exposed to organic solvents and 40 not exposed. All those exposed presented at least 5 years of exposure to solvents. Hepatitis B and C, known hepatic disease, comorbidities, use of alcohol, illicit drugs or hepatotoxic medications, smoking, body mass index >30, female sex and age (<18 or >65) were excluded from the sample. Results indicated that elevated ALT was more frequent in the exposed group compared to controls: 33% vs. 10.5%, with a statistical significance (p < 0.05). Thiobarbituric acid reactive substances were significantly elevated (p < 0.01) in the exposed group in comparison to controls. Antioxidant enzymes were more elevated in the exposed group compared to controls: SOD 7.29 (4.30-8.91) USOD/mg of protein vs. 3.48 (2.98-5.28) USOD/mg of protein and GST 2.57 µmol/min/mg of protein (1.80-4.78) vs. 1.81 µmol/min/mg of protein (1.45- 2.30) µM/min/mg of protein. The results suggest an association between exposure to organic solvents and hepatotoxicity.

GSTM1-null allele predicts rapid disease progression in nondialysis patients and mortality among South Indian ESRD patients.

Chronic kidney disease (CKD) is one of the main causes of early death in humans worldwide. Glutathione S-Transferases (GSTs) are involved in a series of xenobiotics metabolism and free radical scavenging. The previous studies elucidated the interlink between GST variants and to the development of various diseases. The present case-control study performed to ascertain whether GST polymorphisms are associated with the incidence and advancement of CKD. From the Southern part of India, a total of 392 CKD patients (nondialysis, ND; n = 170, end-stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled. Patients were followed-up for 70 months. Serum biochemical parameters were recorded, and the extraction of DNA was done from the patient's blood samples. To genotype study participants, multiplex PCR for GSTM1/T1 was performed. Statistical analysis was carried out to analyze the relationship between gene frequency and sonographic grading, as well as biochemical parameters for disease development. The GSTM1-null genotype showed threefold increased risk (OR = 2.9304; 95% CI 1.8959 to 4.5296; P < 0.0001) to CKD development and twofold increased risk (OR = 1.8379; 95% CI 1.1937 to 2.8299; P = 0.0057) to ESRD progression. During the mean follow-up of 41 months study, multivariate Cox regression analysis revealed that GSTM1-null genotype has 4 times increased the risk for all-cause rapid disease progression to ESRD among ND patients and 3.85-fold increased risk for death among ESRD patients. Survival analysis revealed that patients with GSTM1-present allele showed a significantly diminished risk of mortality compared to patients bearing the GSTM1-null allele among ESRD patients with a hazard ratio of 4.6242 (P < 0.0001). Thus, present data confirm that GSTM1-null genotype increased the risk for all-cause rapid disease progression to ESRD among ND patients. Based on our results, GSTM1-null genotype could be considered as a significant predictor for causing mortality among CKD patients when compared to all other variables.

Oxidant/Antioxidant Status of Breast Cancer Patients in Pre- and Post-Operative Periods.

BACKGROUND AND OBJECTIVES: The purpose of this study is to evaluate the level of oxidative stress before and after breast cancer surgery. MATERIALS AND METHODS: Malondialdehyde (MDA) level was tested using a thiobarbituric acid (TBA) assay based on the release of a color complex due to TBA reaction with MDA. The glutathione S-transferase (GST) activity was evaluated by enzymatic conjugation of reduced glutathione (GSH) with 1-chloro-2,4-dinitrobenzene. The level of total glutathione (reduced GSH and oxidized GSSG) was detected using a recycling system by 5,5-dithiobis(2-nitrobenzoic acid). The levels of the indices were determined in the serum of 52 patients before surgery, two hours and five days after surgery, and in 42 healthy women. RESULTS: In the patients over 50 years old the level of MDA was higher after surgery in comparison with before surgery, and GST activity was lower in comparison with the control. The GSH + GSSG level in both ages groups after surgery was lower than in the control. Significant differences of MDA level were detected in patients with stage III after surgery compared to the control. The level of GSH + GSSG was significantly lower in the patients with I-III stages compared to the control. CONCLUSION: The most expressed changes demonstrate the significance of MDA as a marker to evaluate oxidative stress in breast cancer patients. The degree of oxidative stress depends on the patient's age and stage of disease.

Glutathione-S-transferase: an important diagnostic antigen of liver amphistome Gigantocotyle explanatum, infecting the Indian water buffalo.

The foodborne trematodiases pose a significant health problem to the animals as well as the human population living in close proximities with the livestock and are still considered as the neglected tropical diseases by the World Health Organisation. The digenetic trematode, Gigantocotyle explanatum infecting the liver of Indian water buffalo, Bubalus bubalis, has been identified as one of the most common helminth parasite responsible for the disease, amphistomosis, in livestock. Despite huge abattoir prevalence, the epidemiological data and the actual economic losses incurred due to this parasite alone are yet to be established probably due to the limitations of routinely used diagnostic tests. The gold standard for the confirmation of such infections under field conditions is still the fecal egg count (FEC). However, the poor sensitivity and cumbersome nature of these tests necessitates the development of a more sensitive, reliable and easy to perform workflow/method. Immunological diagnosis of helminthic infections is still considered as an alternative to the FEC. Therefore, efforts have been made to utilize glutathione-S-transferase (GST), a vitally significant molecule of the adult G. explanatum, for the serodiagnosis of amphistomosis under both laboratory and field conditions. The GST antigen was first affinity purified from the somatic extract of the adult worms since its highest level was recorded in the somatic extracts followed by eggs and the excretory/secretory products. A five-fold affinity purified native GST antigen of about 25 kDa was found to be highly immunogenic as evident from high titre (1:25,600) of the polyclonal antibodies raised in the rabbits. The immunoblotting results revealed differential presence of GST in the adult worms, their eggs and excretory/secretory products. The immunolocalization studies revealed that the vitelline glands are the major source of GST in liver amphistome. Further, we were able to successfully screen animals naturally infected with G. explanatum using anti GST polyclonal antibodies in dot blot assay. High levels of both circulating GST antigen and anti GST antibodies were detected in the serum of the animals naturally infected with G. explanatum, while no cross reactivity was observed with the tropical liver fluke, F. gigantica which often infects the buffalo liver concurrently. The findings of the present study indicate that GST could be used as an important antigen for the diagnosis of G. explanatum infection in Indian water buffaloes.

Preliminary evaluation of a novel nine-biomarker profile for the prediction of autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a complex group of heterogeneous neurodevelopmental disorders the prevalence of which has been in the rise in the past decade. In an attempt to better target the basic causes of ASD for diagnosis and treatment, efforts to identify reliable biomarkers related to the body's metabolism are increasing. Despite an increase in identifying biomarkers in ASD, there are none so far with enough evidence to be used in routine clinical examination, unless medical illness is suspected. Promising biomarkers include those of mitochondrial dysfunction, oxidative stress, energy metabolism, and apoptosis. METHODS AND PARTICIPANTS: Sodium (Na+), Potassium (K+), glutathione (GSH), glutathione-s-transferase (GST), Creatine kinase (CK), lactate dehydrogenase (LDH), Coenzyme Q10, and melatonin (MLTN) were evaluated in 13 participants with ASD and 24 age-matched healthy controls. Additionally, five ratios, which include Na+/K+, GSH:GST, CK:Cas7, CoQ10: Cas 7, and Cas7:MLTN, were tested to measure their predictive values in discriminating between autistic individuals and controls. These markers, either in absolute values, as five ratios, or combined (9 markers + 5 ratios) were subjected to a principal component analysis and multidimensional scaling (MDS), and hierarchical clustering, which are helpful statistical tools in the field of biomarkers. RESULTS: Our data demonstrated that both PCA and MDS analysis were effective in separating autistic from control subjects completely. This was also confirmed through the use of hierarchical clustering, which showed complete separation of the autistic and control groups based on nine biomarkers, five biomarker ratios, or a combined profile. Excellent predictive value of the measured profile was obtained using the receiver operating characteristics analysis, which showed an area under the curve of 1. CONCLUSION: The availability of an improved predictive profile, represented by nine biomarkers plus the five ratios, inter-related different etiological mechanisms in ASD and would be valuable in providing greater recognition of the altered biological pathways in ASD. Our predictive profile could be used for the diagnosis and intervention of ASD.

Impact of Escherichia coli infection in broiler breeder chicks: The effect of oxidative stress on weight gain.

The aim of this study was to determine whether oxidative stress occurs in Escherichia coli-infected broiler breeder chicks, as well as the impact of this infection on bird growth. Twenty birds, 25-day-old female birds were divided into two groups (n = 10 per group): an intraperitoneally-infected group (1 mL containing 1.5 × 108 CFU of E. coli) and a control group that received 1 mL of culture medium (uninfected birds). Birds were weighed individually at the beginning and at the end of the experiment, and samples were collected on days 0, 5 and 10 post-infection (PI). No clinical signs were observed throughout the experimental period; nevertheless, on day 10 PI, there was lower growth and weight gain in infected birds than in the control group. The infected birds showed pericarditis and liver congestion, as well as moderate periportal inflammatory infiltrates with predominance of neutrophils. Significantly higher numbers of total leukocytes, lymphocytes, heterophils and monocytes were observed in the infected group on days 5 and 10 PI, as well as significantly higher total protein and globulin levels; albumin values significantly decreased over the same period. Levels of serum oxidative biomarkers (lipid peroxidation (TBARS) and free radicals (ROS)) were significantly higher at 10 PI, as was glutathione S-transferase (GST) activity during the same period. Hepatic ROS and protein thiol levels were significantly higher in E. coli-infected birds, as well as activities of the antioxidant enzymes catalase, superoxide dismutase. In the spleen, only GST activity was significantly higher for the infected group, unlike the brain, where SOD activity, ROS and non-protein thiol levels were significantly higher in infected birds than in the control group. These data suggested that colibacillosis causes oxidative stress in broiler breeder chicks, negatively affecting their weight gain.

Cigarette smoking and antioxidant defences in packed red blood cells prior to storage.

BACKGROUND: Red blood cells from smoking donors can have more lesions from oxidative stress, decreasing the benefits of blood transfusion. We aimed to explore the effect of cigarette smoking on the oxidative status of packed red blood cells (PRBCs) prior to storage. MATERIALS AND METHODS: We compared serum vitamin C, plasmatic malondialdehyde (MDA), and non-protein thiol groups (GSH) levels in PRBCs, as well glutathione peroxidase (GPx) and glutathione s-transferase (GST) activity in PRBCs from smoking (n=36) and non-smoking (n=36) donors. We also correlated urinary cotinine levels with these parameters. RESULTS: Cigarette smoking was associated with decreased serum levels of vitamin C and GPx, and increased GST activity in PRBCs. We found negative correlations between cotinine, GPx activity and vitamin C levels, and a positive correlation between cotinine and GST activity. DISCUSSION: Cigarette smoking changed antioxidant defences of PRBCs prior to storage and these parameters are correlated with cotinine levels. Increased RBC antioxidants such as GST may reflect an exposure to oxidants during erythropoiesis. Because of the inability of mature RBCs to resynthesise antioxidants, PRBCs from smokers may have higher risk of storage lesions than those from non-smoker donors.

FUNCTION OF EXTERNAL RESPIRATION AND MARKERS OF OXIDATIVE STRESS IN CHILDREN-RESIDENTS OF RADIOACTIVELY CONTAMINATED TERRITORIES. / FUNKTsIIa ZOVNIShN'OGO DYKhANNIa I MARKERY OKSYDATYVNOGO STRESU U DITEY̆ ­ MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORIY̆.

OBJECTIVE: to evaluate the influence of processes of lipid peroxidation, and antioxidant protection on the function of external respiration in children-residents of radioactive contaminated territories. MATERIALS AND METHODS: There were examined children of school age, inhabitants of radioactive contaminated ter- ritories (RCT) without respiratory and pulmonary pathology, and patients with bronchial asthma (BA). Examination of the ventilation lung function was performed by the method of pneumotachography according to the analysis of the «flow-volume¼ loop. End products of lipid peroxidation (LPO), reacting with thiobarbituric acid (malondialde- hyde), enzymes-antioxidants - catalase, superoxide dismutase, glutathione peroxidase, glutathione transferase were studied to determine the signs of oxidative stress. RESULTS: Examinations of ventilation lung function in children-residents of RCT without respiratory and pulmonary pathology showed no significant deviations of its parameters beyond the limits of physiological fluctuations; a decrease in bronchial patency at different levels of the bronchial tree was established in children with BA. An increased incidence of bronchial hyperreactivity was noted in both the patients with BA and those who did not have bronchopulmonary pathology. The absence of an increase in the content of LPO products (malondialdehyde) in blood serum of children-residents of RCT with increased activity of catalase and group of glutathione enzymes indi- cates the sufficiency of compensatory possibilities of antioxidant protection. CONCLUSIONS: Studies of correlation between the function of external respiration and markers of oxidative stress determined that the indices of bronchial patency directly correlate with the activity of enzymes-antioxidants of the glutathione group and inversely - with the content of the LPO products in children-residents of RCT. The frequency of bronchospasm inversely correlated with the activity of glutathione group antioxidants. There are inverse correla- tion of 137Cs content in the body with the activity of glutathione transferase and glutathione peroxidase.

The influence of tobacco smoke exposure on selected markers of oxidative stress, kidneys and liver function in the serum of rats with streptozotocin-induced diabetes.

BACKGROUND: The significance of the free radicals is emphasized in the pathophysiology of diabetes and the progression of chronic diabetic complications. Smoking cigarettes increases the risk of developing type II diabetes and intensifies pathophysiological processes during the development of type I diabetes. Tobacco smoke is also additional source of free radicals. Moreover, smoking causes variety of adverse effects on organs, that have no direct contact with the tobacco smoke itself. The objective of the study was to examine the effects of tobacco smoke on the serum concentrations of relevant oxidative stress markers such as total protein (TP), reduced glutathione (GSH), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS), as well as renal (creatinine, urea) and liver function (alkaline phosphatase, ALP; alanine aminotransferase, ALT; aspartate aminotransferase, AST) among animals with induced diabetes after administration of a single dose of streptozotocin (65 mg/kg, ip). METHODS: The markers of oxidative stress and biochemical parameters were determined using spectrophotometric methods. As a biomarker of exposure to tobacco smoke, cotinine was determined using high-performance liquid chromatography with diode array detection (HPLC-DAD). RESULTS: Tobacco smoke exposure of diabetic rats was manifested by significantly elevated liver enzymes activity - ALT (p < 0.05) and ALP (p < 0.01), higher creatinine and urea concentration (p < 0.01), lower GSH amount (p < 0.05), and higher GST activity (p < 0.05). CONCLUSIONS: Tobacco smoking induce liver and renal damage through the mechanisms including increased oxidative stress.