Serum paraoxonase, arylesterase, and glutathione-s-transferase activities and oxidative stress levels in patients with mushroom poisoning

OBJECTIVES: Consumption of toxic species of mushrooms may have detrimental effects and increase oxidative stress. Paraoxonase, arylesterase and glutathione-S-transferase are antioxidants that resist oxidative stress. In this study, we analyzed the changes in these enzymes during intoxication due to mushrooms. METHODS: The study enrolled 49 adult patients with a diagnosis of mushroom poisoning according to clinical findings and 49 healthy volunteers as the control group. The patients with mild clinical findings were hospitalized due to the possibility that the patient had also eaten the mushrooms and due to clinical findings in the late period, which could be fatal. Paraoxonase, arylesterase, and glutathione-S-transferase concentrations, as well as total antioxidant and oxidant status, were determined in the 49 patients and 49 healthy volunteers by taking blood samples in the emergency department. RESULTS: While paraoxonase, arylesterase, and total antioxidant status were significantly decreased in the patient group (p<0.05), glutathione-S-transferase, total oxidant status and the oxidative stress index were significantly higher (p<0.05). There was a positive correlation between the hospitalization time and the oxidative stress index (r=0.752, p<0.001), whereas a negative correlation was found with glutathione-S-transferase (r=-0.420, p=0.003). CONCLUSION: We observed a significant decrease in paraoxonase and arylesterase and an increase in glutathione-S-transferase and oxidative stress indexes in patients with mushroom poisoning, indicating that these patients had an oxidative status. In particular, a low total antioxidant status and high oxidative stress index may gain importance in terms of the assessment of hospitalization duration.

Acute toxicity and cholinesterase inhibition of the nematicide ethoprophos in larvae of gar Atractosteus tropicus (Semionotiformes: Lepisosteidae)

Biomarkers are a widely applied approach in environmental studies. Analyses of cholinesterase (ChE), glutathione S-transferase (GST) and lipid peroxidation (LPO) are biomarkers that can provide information regarding early effects of pollutants at different biochemical levels on an organism. The aim of this study was to evaluate the biomarker approach on a Costa Rican native and relevant species. For this, larvae of gar (Atractosteus tropicus) were exposed to the organophosphorus nematicide, ethoprophos. Acute (96hr) exposure was conducted with pesticide concentrations ranging from 0.1μg/L to 1 500μg/L. The 96hr LC50 calculated was 859.7μg/L. After exposure, three biomarkers (ChE, GST and LPO) were analyzed in fish that survived the acute test. The lowest observed effect concentration (LOEC) regarding ChE activity inhibition was 50μg/L. This concentration produced a significant inhibition (p<0.05) of the enzyme by 20%. The highest concentration tested without showing any effect on ChE activity and therefore considered as no observed effect concentration (NOEC) was 10μg/L. Ethoprophos concentration of 400μg/L caused a ChE inhibition by 79%. In this study, no significant variations (p>0.05) in GST activity and LPO were observed in A. tropicus larvae after exposure to ethoprophos.

El proceso de reproducción inducida de Atractosteus tropicus es útil para la acuicultura y la reintroducción en zonas donde las poblaciones silvestres se han reducido considerablemente. En larvas de esta especie se evaluó la toxicidad aguda, así como la respuesta de tres biomarcadores: actividad colinesterasa (ChE), actividad de Glutation S-transferasa (GST) y peroxidación de lípidos (LPO). Asimismo, se realizaron exposiciones agudas (96hr) a etoprofos (nematicida organofosforado), en donde se utilizaron concentraciones entre 0.1μg/L y 1 500μg/L del nematicida. La concentración letal 50 (LC50) calculada fue de 859.7μg/L; la máxima concentración sin efecto en los organismos (NOEC) 10μg/L y la concentración más baja en la cual se observó algún efecto (LOEC) 50μg/L. A esa concentración, el efecto observado fue una reducción significativa (p<0.05) en la actividad de la ChE. Una concetración de etoprofos de 400μg/L causó una inhibición del 79% en la actividad ChE. La actividad GST y la LPO no mostraron una respuesta significativa (p>0.05) luego de la exposición de los organismos a etoprofos.

possible role of Petroselinum Sativum extract against oxidative stress in CCL[4]-induced hepatotoxicity in albino rats

The present study investigated the possible effect of the ethanolic extract of Petroselinum sativum against CCl[4]-induced hepatotoxicity in rats and compared with Rutin as reference. Ethanolic extract of Petroselinum sativum in two concentrations 100 and 200 mg/kg.bw. Was orally administered for 21 days after i.p CCl[4] injection to evaluate its possible effect. Also, Rutin [as standard antioxidant] was orally administered by concentration of 200 mg/kg.bw. Malondialdehyde "MDA" concentration [the end product of lipid peroxide] and total protein were determined both in liver, homogenate and plasma. Reduced Glutathione "GSH" content was determined in liver homogenate and in whole blood. Albumin was also determined and Glutathione-S-transferase "GST" in serum of rats was performed. Histological studies of liver for all treatments were investigated and results revealed that, the lipid peroxides "MDA" and "GST" were significantly increased [p<0.05], while reduced glutathione was decreased after treatment of CCL[4]. Administration of Petroselinum Sativum ethanolic extract at two concentrations and Rutin exerted a significant decreases [p<0.05] in MDA concentration, while the reduced glutathione appeared to be increased in whole blood. The activity of GST was reduced due to the effect of Petroselinum Sativum and Rutin after the duration time [10 and 21 days]. The ethanolic extract of Petroselinum Sativum revealed a significant increase in the total protein, albumin, and A/G ratio. The histological studies showed a significant increase in liver injury of intoxicated rats. After treatment with ethanolic extract of Petroselinum Sativum as well as Rutin, the sites of injury were decreased. It was concluded that, the toxic effect of CCl[4] on liver was abrogated under the effect of Petroselinum Sativum ethanolic extract; also, Rutin had an inhibitory effect on lipid peroxidation. These findings suggested that the plant extract of Petroselinum Sativum could has a potent antioxidant activity

Downregulation of Orai1 expression in the airway alleviates murine allergic rhinitis

Orai1 is the key subunit of the Ca2+-release-activated Ca2+ channel. Our previous report has demonstrated that Orai1 expression in the airway was upregulated in the ovalbumin (OVA)-induced allergic rhinitis (AR) mouse models. To observe whether inhibition of Orai1 expression in the airway could suppress symptoms in a murine model of AR and to assess the impacts of this inhibition on the responses of local and systemic immunocytes, we administered recombinant lentivirus vectors that encoded shRNA against ORAI1 (lenti-ORAI1) into the nostrils of OVA-sensitized mice before the challenges, and analyzed its effect on allergic responses, as compared with the unsensitized mice and untreated AR mice. Administration of lenti-ORAI1 into the nasal cavity successfully infected cells in the epithelial layer of the nasal mucosa, and significantly decreased the frequencies of sneezing and nasal rubbing of the mice. Protein levels of leukotriene C4, OVA-specific IgE, and IL-4 in the nasal lavage fluid and serum and eosinophil cation protein in the serum were also significantly reduced by lenti-ORAI1, as were the mRNA levels of these factors in the nasal mucosa and spleen. These data suggested that administration of lenti-ORAI1 into the nasal cavity effectively decreased Orai1 expression in the nasal mucosa, alleviated AR symptoms, and partially inhibited the hyperresponsiveness of the local and systemic immune cells including T cells, B cells, mast cells and eosinophils that are involved in the pathogenesis of AR.

Lipid profile and oxidative stress status in vegetarians

To investigate the lipid profile and oxidative stress status in vegetarians and non-vegetarians. Fifty healthy volunteered adults, 25 vegetarians and 25 non-vegetarians [meat eaters] ages 20-50 Years from Babcock University community were recruited for this study. Venous blood sample was collected pre meal and two hours post-prandial for biochemical assay. We assayed for the plasma levels of total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, protein content, superoxide dismutase [SOD], catalase [CAT], glutathione s-transferase [GST], reduced glutathione [GSH]. Data collected were subjected to statistical analysis using the Student's t-test and one way ANOVA with the aid of SPSS for windows version 14.0. P<0.05 was considered statistically significant. Lipid profile analysis showed non-vegetarians to be significantly higher [P<0.05] in total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol than vegetarians respectively. Plasma protein concentration was significantly higher [P<0.05] in vegetarians [1.23 +/- 0.29; 1.22 +/- 0.18] than non-vegetarians [0.83 +/- 0.09; 0.84 +/- 0.17] in pre and post meal respectively. Furthermore, plasma superoxide dismutase [0.25 +/- 0.72; 0.35 +/- 1.60] and catalase activities [0.04 +/- 0.00; 0.01 +/- 0.27] were significantly reduced [P<0.05] in vegetarians than SOD [0.93 +/- 1.80; 0.63 +/- 1.52] and CAT [0.08 +/- 0.24; 0.02 +/- 0.05] in non-vegetarians in pre and post meal respectively. More so, non-vegetarians expressed a higher level of reduced glutathione [0.05 +/- 0.00] post meal than vegetarians [0.02 +/- 0.00]. Glutathione S-transferase activity was found to be higher in vegetarians [460.28 +/- 44.77] than non-vegetarians [100.61 +/- 79.28] after meal. Vegetarians may have lower lipid and oxidative stress status than non-vegetarians

Assessment of the protective role of green tea on doxorubicin induced hepatic and renal injuries in albino rats

The present study has been undertaken to investigate the ameliorative effect of green tea [GT] on doxorubicin [Doxo]-induced hepatotoxicity and nephrotoxicity in albino rats. The harmful effects of Doxo on some antioxidant enzymes, catalase [CAT], superoxide dismutase [SOD] and glutathione-S-transferase [GST] were studied. Reduced glutathione [GSH] and malondialdehyde [MDA] in liver and kidney homogenates were investigated. Quantitative and qualitative extents of DNA damage in the liver cells were also estimated using Cornet assay. Thirty two male adult albino rats [180-200 g] were divided into four groups [n=8] as follows; [1] Control group: was orally administered 1 ml/rat of 0.5% carboxymethyl cellulose [CMC] in distilled water, [2] Doxo group: after 10 days, Doxo was administered a single i.p. dose of 15 mg/kg body weight, [3] GT group: rats received 100 mg/kg body weight, p.o. of GT for 10 days and [4] Doxo and GT group: rats received 100 mg/kg body weight, p.o. of GT for 10 days prior to Doxo administration as a single i.p. dose of 15 mg/kg body weight. Doxorubicin-induced significant increase in serum levels of AST, ALT and gamma-glutamyl transpeptidase [GGT] for liver and urea and creatinine for kidney which were decreased by pretreatment with GT. Total serum protein and albumin levels were decreased after treatment with Doxo but this effect was attenuated by pretreatment with GT. Catalase, SOD, GST activities and GSH content of liver and kidney were significantly elevated by pretreatment with GT compared to Doxo-treated rats. Doxorubicin significantly increased in MDA levels. DNA damage measured as tail length, tail DNA% and tail moment were increased after treatment of Doxo while pretreatment with GT improved this effect. This study suggests that green tea has potential protective effect against doxorubicin-induced hepatoxicity and nephrotoxicity. So, it may be worthy to consider the usefulness of GT as adjuvant therapy in cancer management

Beneficial effects of n-acetyl cysteine on pancreas and kidney following experimental pancreatic ischemia-reperfusion in rats

OBJECTIVE: To evaluate the protective effects of N-acetyl cysteine on the pancreas and kidney after pancreatic ischemia reperfusion injury in a rat model. METHODS AND MATERIALS: Pancreatic ischemia reperfusion was performed in Wistar rats for 1 hour. Revascularization was achieved followed by 4 h of reperfusion. A total of 24 animals were divided into four groups: Group 1: sham; Group 2: pancreatic ischemia reperfusion without treatment; Group 3: pancreatic ischemia reperfusion plus N-acetyl cysteine intravenously; and Group 4: pancreatic ischemia reperfusion plus N-acetyl cysteine per os. Blood and tissue samples were collected after reperfusion. RESULTS: There were significant differences in amylase levels between Group 1 (6.11±0.55) and Group 2 (10.30±0.50) [p=0.0002] as well as between Group 2 (10.30±0.50) and Group 4 (7.82±0.38) [p=0.003]; creatinine levels between Group 1 (0.52 ± 0.07) and Group 2 (0.77±0.18) [p=0.035] as well as between Group 2 (0.77±0.18) and Group 3 (0.48±0.13) [p=0.012]; and pancreatic tissue thiobarbituric acid reactive substance levels between Group 1 (1.27±0.96) and Group 2 (2.60±3.01) [p=0.026] as well as between Group 2 (2.60±3.01) and Group 4 (0.52±0.56) [p=0.002]. A decrease in pancreatic tissue GST-á3 gene expression was observed in Group 2 in comparison to Group 1 (p =0.006), and an increase was observed in Groups 3 and 4 when compared to Group 2 (p= 0.025 and p=0.010, respectively). CONCLUSION: This study provides evidence that N-acetyl cysteine has a beneficial effect on pancreatic ischemia reperfusion injury and renal function in a rat model.

Postconditioning ameliorates lipid peroxidation in liver ischemia-reperfusion injury in rats / Pós-condicionamento melhora a peroxidação lipídica na lesão de isquemia-reperfusão hepática em ratos

PURPOSE: Liver ischemia-reperfusion injury is a phenomenon presents in events like liver resections and transplantation. The restoration of blood flow may leads to local and systemic injury. Several techniques have been developed in order to avoid or ameliorate ischemia-reperfusion injury in clinical situations. The application of a sttuter reperfusion after the ischemic event (postconditioning) could alters the hydrodynamics and stimulates endogenous mechanisms that attenuate the reperfusion injury. The present study was designed to evaluate the potential protective effect of postconditioning in a model of ischemia-reperfusion in rats. METHODS: Hepatic anterior pedicle of median and left anterolateral segments were exposed and clamped for 1 hour. Two hours later, clamp was released in two different ways: Control Group (n=7): clamp was release straightforward; Postconditioning Group (n=7): clamp was released intermittently. Lipid peroxidation (malondialdehyde) and expression of the glutathione-s-transferase-α-3 gene were studied. RESULTS: Lipid peroxidation was significantly decreased in ischemic and non-ischemic liver by postconditioning. GST- α3 gene was overexpressed in postconditioned group, but not significantly. CONCLUSION: Postconditioning induced hepatoprotection by reducing lipid peroxidation in the ischemic and non-ischemic liver.

OBJETIVO: A lesão de isquemia-reperfusão hepática é um fenômeno presente em eventos tais como ressecções hepáticas e transplante de fígado. A restauração do fluxo sangüíneo após a isquemia gera lesões locais e sistêmicas. Várias técnicas foram desenvolvidas com o objetivo de evitar ou diminuir a lesão de isquemia-reperfusão hepática em situações clínicas. A utilização da reperfusão intermitente após o evento isquêmico (pós-condicionamento) pode alterar a hidrodinâmica e estimular mecanismos endógenos que atenuam o dano da reperfusão. O presente estudo foi realizado para avaliar o potencial efeito protetor do pós-condicionamento em um modelo de isquemia-reperfusão em ratos. MÉTODOS: O pedículo dos lobos mediano e ântero-lateral foi isolado e clampeado por 1 hora. Após 2 horas, o pedículo foi liberado de duas maneiras diferentes: Grupo Controle (n=7): clampe liberado de uma só vez; Grupo Pós-condicionamento (n=7): clampe liberado de maneira intermitente. Malondialdeído (MDA) e expressão do gene GST- α3 foram estudadas nos grupos. RESULTADOS: A peroxidação lipídica foi significativamente diminuída no fígado isquêmico e no fígado não isquêmico pelo pós-condicionamento. A expressão do gene GST- α3 aumentou, porém não significativamente, no grupo pós-condicionamento. CONCLUSÃO: O pós-condicionamento induziu hepatoproteção pela redução da peroxidação lipídica nos fígados isquêmico e não isquêmico.

Time-dependent effects of ethanol on blood oxidative stress parameters and cytokines.

Alcohol consumption is implicated in the genesis of a spectrum of liver abnormalities, which are associated with a number of factors. In the present study, time-dependent effects of ethanol on cytokines (TNF-alpha, IL-2, IL-4, IL-10, IFN-gamma, VEGF-A and TGF-beta1) in serum, and blood oxidative stress parameters such as reduced glutathione content, TBARS level and activities of GPx, GR, GST, catalase and SOD in 8-10 weeks-old male BALB/c mice have been investigated. Ethanol administered @ 1.6 g/kg body wt/day significantly increased the activities of liver marker enzymes AST, ALT and ALP. Serum nitrite levels and haemolysate TBARS level also increased, while total antioxidant status in serum and GSH content in whole blood hemolysate decreased from 4th week onwards of exposure. In spite of the increased serum nitrite level and GST activity in the haemolysate, albumin level in serum, GPx and GR activities in haemolysate decreased after 12 weeks of exposure. Chronic ethanol treatment did not show any effect on IL-2, but IL-4 level was reduced and other cytokines such as IL-10, TNF-alpha, IFN-gamma, TGF-beta1 and VEGF-A levels were increased significantly after 12 weeks. The study indicates a relationship between free radical generation and immune response, and suggests that ethanol-induced liver damage is associated with oxidative stress and immunological alterations in a time-dependent manner.

Detoxifying and anti-oxidant enzymes of Fasciola gigantica worms under triclabendazole sulphoxide [TCBZ-SX]: An in vitro study

Triclabendazole [TCBZ] is an efficient fasciolicide that affects both juvenile and adult worms. After oral administration it is rapidly metabolized to TCBZ sulphoxide and sulphone that were found responsible for its fasciolicidal activity. Parasite defense mechanisms include detoxifying and anti-oxidant enzymes that would suppress its oxidative killing. The present work aimed at evaluating these enzymes under TCBZ-SX. Thirty juvenile and 30 adult F. gigantica worms collected from the liver parenchyma and bile ducts formed the subject of the study. Levels of superoxide dismutase [SOD], glutathione peroxidase [GPx], glutathione reductase [GR], glutathione S-transferase [GST], and glutathione [GSH] were measured in juvenile and adult worms incubated, without and with 15 and 50 micro g/ml TCBZ-SX for 18 hours at 37°C. Results demonstrated a significant decrease in SOD activity and an increase in GST level in both juvenile and adult worms after incubation in the two concentrations. The remaining enzymes and GSH revealed variable levels

Genetic polymorphism of glutatfflone-s- transferase and susceptibility to and severity of chronic obstructive pulmonary disease

Chronic tobacco smoking is a major risk factor in the development of COPD. However, it is estimated that only 10-20% of chronic heavy smokers will develop symptomatic COPD. This indicates the possible contribution of environmental or genetic cofactors to the development of COPD in smokers. The present work aimed to study the relationship between GST polymorphism and susceptibility to and severity of COPD in smokers. A case control study was done on 140 patients with COPD and 140 matched controls. All subjects were smokers or exsmokers. The GSTM1 and GSTT1 genotypes were identified by polymerase chain reaction in peripheral blood DNA samples. Analysis of data was done by IBM computer using SPSS program. Results shown that the proportion of GSTMl-null genotypes was significantly higher in patients with COPD than in control subjects [62.2% versus 32.2%]. The odds ratio was 3.5 [95% confidence interval [CI] = 2.1-5.7]. Moreover the patients with GSTM1 null genotype were at high risk of developing the severe type of COPD. The odds ratio was 3.2 and [95% CI = 1.5-6.7]. However the genotype frequencies of GSTTl-null genotype did not show significant difference between groups. Our data provide evidence that smokers with null genotype of GSTM1 were more susceptible to develop the severe type of COPD

Antioxidant status and lipid peroxidation activity in evaluating hepatocellular damage in children

Serum levels of glutathione reductase [GR], glutathione S-transferase-alpha [GST-alpha] and malondialdehyde [MDA] were determined to evaluate their use in diagnosing hepatocellular damage in 75 children with liver disease. Except for level of GR in patients with HBV, GR, GST-alpha and MDA were raised significantly in patients compared with controls. At 100% specificity, the sensitivity of the 3 markers for detecting hepatitis B virus, hepatitis C virus and schistosomiasis infection respectively were: 16.7%, 100.0% and 17.7% for GR; 33.3%, 62.1% and 38.2% for GST-alpha; and 25.0%, 10.3% and 29.4% for MDA. GR was more sensitive in hepatitis C infection, while MDA reflected changes in liver ultrasound and GST-alpha was the best indicator for histopathological changes

Alpha-glutathione S-transferase and serum aminotransferases in Schistosomiasis mansoni patients with or without hepatitis C virus

The present study evaluated delta-Glutathione-S-transferase as a biochemical marker for hepatocellular damage in schistosomiasis mansoni patients, with or without chronic hepatitis C [HCV] patients as compared to controls. Alpha GST, ALT and AST were assayed in sera of GI: 20 schistosomiasis mansoni patients with HCV, GII 16 schistosomiasis mansoni patients without HCV, GIII 19 pure HCV patients and GIV: 20 normal controls. The results showed that delta-Glutathione-S-transf erase was less sensitive and less specific but more accurate than ALT and AST as a liver affection marker in HCV patients

Glutathione S-transferase genetic polymorphisms as possible risk factors for hepatocellular carcinoma in Egyptian population

High rates of hepatocellular carcinoma [HCC] are primarily due to high prevalence of chronic hepatitis C or B virus infection which causes chronic necroinflammatory hepatic disease. Egypt has one of the world's highest prevalences of hepatitis C virus [HCV] infection. Glutathione S-transferases [GSTs] constitute a superfamily of enzymes that catalyse the metabolism of a wide range of carcinogens. Of the different isoforms of GSTs, GSTM1 and GSTT1 which have deletion polymorphisms. The aim of the present study was to investigate the possible association between GSTM1 and GSTT1 deletion polymorphisms and the risk of HCC in Egyptian patients with hepatitis C virus [HCV] infection. Subjects and The genotypes of GSTM1 and GSTT1 were analyzed in 24 HCV carriers with HCC, and 25 healthy controls using polymerase chain reaction [PCR] technique. The null genotypes of GSTM1 and GSTT1were significantly frequent in patients with HCC compared with controls. These results suggest that both The GSTM1 and GSTT1 null genotypes are associated with an increased risk of HCC in Egyptian population

Serum total glutathione-s-transferase levels in oral cancer.

We conducted a study wherein serum total glutathione-s-transferase levels were measured in patients (n = 27) with various stages of biopsy proven oral cancer (squamous cell carcinoma) and age and sex matched healthy human volunteers (n=10). In all patients with oral cancer, serum total glutathione-s-transferase was measured before the onset of treatment. There was a significant increase in serum total glutathione-s-transferase levels in patients with stage IV oral cancer as compared to stage II (P = 0.001) and stage III (P = 0.002) oral cancer. This shows that alterations in serum total Glutathione-s-transferase levels may have a role in cancer progression.

Glutathione S-transferase gene T1 and ml polymorphism in type 2 diabetic patients with end-stage renal disease

Diabetes mellitus [DM] is associated with an increased production of reactive oxygen species [ROS] which may contribute to the development of diabetic nephropathy. Therefore, the levels of endogenous antioxidants may be one of determinants of the susceptibility to diabetic nephropathy. Glutathione S-transferases [GSTs] are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. Genetic polymorphisms of the genes coding for enzymes result in different phenotypes with respect to their ability to detoxify these agents. The present study was conducted to determine whether GSTM1 and GSTTl gene polymorphism influences the development of diabetic nephropathy in type 2 DM. The study population consisted of 80 subjects divided into 30 patients type 2 DM with diabetic related end-stage renal diseases [ESRD], 30 patients type 2 DM without nephropathy and 20 subjects apparently healthy individuals as a controls. Multiplex polymerase chain reaction [PCR] was used to analyze GSTM1 and GSTTl polymorphism. GSTTl and GSTM1 gene polymorphism occur more in diabetic patients with ESRD than diabetic patients without nephropathy [GSTM1 null genotype was present in 63% while GSTTl null genotype was present in 60% in group I]. Frequency of homozygous deletion of both GSTTl, GSTM1 was higher in diabetic patients with ESRD [53%] than patients without ESRD [10%], or control [5%], [p<0.05]. Significant negative correlation was found between presence of/GSTMl, GSTTl and albuminuria, serum creatinin and blood urea in diabetic patients with ESRD with a positive correlation between presence of gene GSTTl and GSTM1 null genotype and creatinine clearance where creatinine clearance was lower in patients with GSTT1and GSTM2 deletion, GSTM1 and GSTTl null genotype may play a significant role in the aetiopathogeneses and development of diabetic ESRD and may be a useful marker in the prediction of diabetic ESRD. Also, it can drive approch of genetic therapy in prevention of diabetic nephropathy

Antioxidant enzyme activities and lipid peroxides in erythrocytes in patients with benign prostate hyperplasia and prostate cancer

To investigate the possible alteration of oxidant-antioxidant status in the erythrocytes of patients with benign prostate hyperplasia and prostate cancer. Malondialdehyde [MDA], an index of lipid peroxidation, the enzyme activities of superoxide dismutase [SOD], glutathione peroxidase [GPx], glutathione S-transferases [GSTs], catalase [CAT] and reduced glutathione [GSH] levels were estimated in the erythrocytes of 30 prostate cancer [PC] patients, 35 benign prostate hyperplasia [BPH] patients and 28 age-and sex-matched healthy controls. MDA level and GSTs activity levels were significantly increased, while GPx, SOD activities and the level of reduced GSH concentration were significantly decreased in the prostate cancer group versus controls [p<0.001] and BPH group [p<0.05]. The relatively higher GSTs activity and low level of reduced GSH may be due to the response of increased reactive oxygen metabolites production in the blood. The higher MDA level and lower GPx and SOD activities may be inadequate to detoxify high levels of H[2]O[2] into H[2]O leading to the formation of [asterisk]OH radical followed by the formation MDA. Oxidant-antioxidant imbalance may be one of the major factors responsible for the development of prostate cancer and benign prostate hyperplasia

Glutathione and related enzymes in Egyptian bladder cancer patients

Enzymes metabolizing foreign compounds may modify the risk of chemically induced bladder cancer. The aim of the present work was to determine the level of detoxifying macromolecules and activities of detoxifying enzymes, namely; glutathione [GSH], glutathione S-transferase pie [pi-GST], glutathione peroxidase [GPx], and glutathione reductase [GR] in blood of bladder cancer patients; as well as; groups at high risk for this type of cancer who are subjected to environmental chemical pollution such as smoking and biological pollution such as schistosomiasis. The ultimate goal of the study is to search among these parameters for a marker that could be of value in detection of bladder cancer or at least might have a role in selecting individuals that are at high risk for bladder cancer. A total of eighty individuals were included in the present study. They were divided into 4 groups: Healthy normal subjects as control group, Smoking group, Schistosomal patients group, and Bladder cancer patients group. All the parameters were determined either by spectrophotometric or ELISA technique. Glutathione level, Pi-GST and GR activities were slightly elevated among smokers and schistosomal patients. Nevertheless, their levels were highly significantly elevated in sera of bladder cancer patients as compared with their corresponding levels among the other groups [p<0.001]. Beside, pi-GST was elevated in cases with squamous cell carcinoma [SCC] more than those with transitional cell carcinoma [TCC]. However, GPx showed no significant changes among all investigated groups [p=0.122]. We suggest that the values of GSH, pi-GST and GR activities could be added to tumor markers for bladder cancer detection, or at least for indicating groups who are at high risk to put them under medical surveillance

Recuperação autóloga de sangue intra-operatória: validação com marcador tumoral específico em câncer de próstata / Intraoperative Autologous Blood Recovery: validation with a specific tumour marker in prostate cancer

INTRODUÇÃO: Padrões de metilação aberrante em amostras de DNA de pacientes com câncer são marcadores moleculares sensíveis. A hipermetilação na região promotora de GSTP-1 está presente em mais de 90% dos pacientes com câncer de próstata e pode ser avaliada através de técnicas de PCR. A recuperação autóloga intra-operatória durante cirurgia oncológica não tem sido recomendada devido ao risco de células tumorais estarem circulantes neste sangue. Nosso objetivo é demonstrar que o sangue recuperado de cirurgia oncológica pode estar livre de células tumorais após a utilização de filtros para remoção de leucócitos e irradiação, através da hipermetilação do promotor de GSTP-1 como marcador. MÉTODOS: Realizamos recuperação autóloga intraoperatória em prostatectomia radical sem a reinfusão do sangue. Somente os casos com hipermetilação do promotor de GSTP-1 nas amostras de tumor fresco foram incluídas. Uma amostra de sangue periférico foi colhida na indução anestésica. O sangue recuperado foi colhido ao longo da cirurgia e então submetido à lavagem; filtração e irradiação (25 Gy). As amostras foram estudadas em cada etapa para detectar a presença de células de tumor de próstata contaminantes, através de ensaios qualitativos e de “real time” PCR metilação específica. RESULTADOS: Detectamos células de tumor de próstata no sangue recuperado através da presença de metilação para GSTP-1 nos ensaios de PCR qualitativos. Após filtração e irradiação as análises de “real time” PCR confirmaram a ausência de metilação, sugerindo a ausência de células viáveis. DISCUSSÃO: Utilizando uma abordagem epigenética não evidenciamos célula tumoral viável ou DNA no sangue recuperado desses pacientes após filtração e irradiação. Esses resultados apontam para a segurança da recuperação de sangue associando filtração e irradiação em cirurgia oncológica...

INTRODUCTION: Aberrant DNA methylation patterns provide a powerful sensitive detection molecular marker to cancer. GSTP-1 hypermethylation is present in more than 90% of prostate cancer patients and can be measured by PCR-based techniques. Blood salvage during cancer surgery is limited due to the potential presence of circulating tumour cells. We aimed to show that intraoperative salvaged blood can be freed of tumour cells after leucodepletion filters and irradiation of washed blood using GSTP-1 hypermethylation as a biomarker. METHODS: We performed intraoperative blood recovery in radical prostatectomy without reinfusion. Only cases with GSTP-1 hypermethylation in the fresh tumour samples were included. A peripheral blood sample was collected during anaesthesia induction. Salvaged blood was collected throughout the surgery and then submitted to washing, leukoreduction and irradiation. Samples were studied stepwise for the presence of prostate tumour cell contamination using qualitative and realtime methylation specific PCR. RESULTS: Prostate tumour cells detected by positive results for GSTP-1 in washed salvaged blood became negative after filtration and irradiation in qualitative PCR. It was confirmed by quantitative assay, thus suggesting the absence of viable cells. DISCUSSION: Using an epigenetic approach no tumour viable cell or DNA was found in the salvaged blood of these patients after filtration and irradiation (25Gy). These results point to the safety of blood salvage with filtration and irradiation in cancer surgery (AU)

Lipid peroxidation and antioxidant status in patients with carcinoma of prostate.

Prostate cancer is the most prevalent cancer found in men above the age of fifty years and is frequently diagnosed in men between 45 and 89 years of age with a median age of 72 years. This work was undertaken to assess oxidative stress and anti oxidant status in patients with carcinoma of prostate. Glutathione (GSH), Malondialdehyde (MDA), Super Oxide Dismutase (SOD) levels in Erythrocytes and plasma Glutathione-S-Transferase (GST) levels were estimated in patients with carcinoma of prostate and compared to controls. It was observed that Erythrocyte GSH levels were significantly lower and Erythrocyte MDA & SOD levels were significantly higher in patients with carcinoma of prostate compared to controls. No significant change was observed in case of GST compared to controls. Oxidative stress may be involved in prostate cancer as evidenced by the higher MDA levels and lower GSH levels. The increased activity of antioxidant enzyme may be a compensatory regulation in response to oxidative stress.