Glutathione S-transferase genetic polymorphisms and fluoride-induced reproductive toxicity in men with idiopathic infertility / 亚洲男科学杂志(英文版)

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.

Avaliação dos níveis da citocina pró-inflamatória fator de necrose tumoral-α em pacientes com diabetes tipo 2 e sua relação com variações genéticas de enzimas antioxidantes e obesidade / Evaluation of proinflammatory cytokine tumor necrosis factor-α levels in obese vs nonobese patients with type 2 diabetes and their relationship to CAT C-262T polymorphism

Introdução: Diabetes tipo 2 (DM2) é um distúrbio multifatorial caracterizado pelo aumento dos níveis de radicais livres. Tanto o estresse oxidativo quanto a obesidade contribuem para um estado inflamatório da doença, principalmente pelo aumento da citocina TNF-α. Sabendo-se que a genética individual pode contribuir para o estresse oxidativo, o estudo avaliou o impacto das variações genéticas de enzimas antioxidantes C262T no gene CAT e polimorfismos nulos dos genes GSTM1 e GSTT1 nos níveis de TNF-α, assim como, avaliou se as variantes genéticas atuariam sinergicamente com a obesidade aumentando os níveis da citocina em diabéticos da Grande Vitória/ES, Brasil.Métodos: O polimorfismo no gene CAT foi avaliado pela técnica PCR/RFLP e nos genes GSTM1 e GSTT1 por PCR multiplex, em 56 pacientes, sendo 28 obesos e 28 não obesos. Níveis de TNF-α foram medidos pela técnica de ELISA sanduíche.Resultados: Frequências das variantes nulas de GSTM1 e GSTT1 foram 44,6% e 17,9%, respectivamente. As frequências genotípicas C262T-CAT foram 73,2%, 25% e 1,8% para homozigoto normal, heterozigoto e homozigoto polimórfico, respectivamente. Não houve associação entre genótipos polimórficos e aumento dos níveis de TNF-α, assim como, não foi demonstrado aumento significante da citocina quando avaliado o sinergismo entre obesidade e genética individual do paciente.Conclusão: Níveis de TNF-α não se elevam em diabéticos tipo 2 na presença dos polimorfismos nos genes CAT, GSTM1 e GSTT1, e a obesidade não atua no aumento dessa citocina na população estudada, separadamente ou em conjunto com a genética individual de variantes nos genes CAT, GSTM1 e GSTT1.

Introduction: Type 2 diabetes is a multifactorial disorder characterized by increased levels of free radicals. Both oxidative stress and obesity contribute to an inflammatory state of the disease, mainly by increasing the levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α). Considering that personal genetics may contribute to oxidative stress, this study assessed the impact of CAT C-262T polymorphism and GSTM1 and GSTT1 null polymorphisms on TNF-α levels in patients with type 2. diabetes. The study also evaluated whether the genetic variants act synergistically with obesity to increase TNF-α levels in patients with diabetes from Grande Vitória, Brazil.Methods: Fifty-six patients were included, of whom 28 were obese and 28 were nonobese. The CAT gene polymorphism was assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, whereas GSTM1 and GSTT1 polymorphisms were assessed using multiplex PCR. TNF-α levels were measured using the sandwich ELISA technique.Results: Frequencies of GSTM1 and GSTT1 null polymorphisms were 44.6% and 17.9%, respectively. The genotype frequencies of CATC-262T polymorphism were 73.2%, 25.0%, and 1.8% for normal homozygote, heterozygote, and polymorphic homozygote, respectively. Polymorphic genotypes were not associated with increased TNF-α levels, and there was no significant increase in TNF-α levels when evaluating the synergism between obesity and personal genetics.Conclusion: The presence of CAT, GSTM1, and GSTT1 gene polymorphisms was not associated with increased TNF-α levels in patients with type 2 diabetes. Obesity alone or combined with personal genetics of CAT, GSTM1, and GSTT1gene polymorphisms did not promote increased TNF-α levels in the study population.

Glutathione S-Transferase Activity in Tissues of Rats Exposed to Fenarimol

Abstract The unconscious use of pesticides causes various adverse effects on non-target organisms, including humans. Enzymes that control metabolism become the target of the pesticide and the organs are damaged due to toxic effects. Glutathione s-transferase (GST, EC 2.5.1.18), an important enzyme of the detoxification mechanism and antioxidant defense system, can be affected by such toxic substances. Therefore, the effect of fenarimol on GST enzyme activity was investigated in our study. For this, 200 mg/kg fenarimol was administered intraperitoneally to male and female rats at different periods (2, 4, 8, 16, 32, 64 and 72 hours). After application, GST enzyme activity was analysed in the liver, kidney, brain and small intestine tissues of the rats. According to our results, activation (liver, kidney, small intestine) or inhibition (brain) of the generally GST enzyme was observed in the tissues of rats exposed to fenarimol. It is thought that the increase and/or decrease in this enzyme activity may be the cause of the toxic effect of fenarimol.

Acute toxicity of a deltamethrin based pesticide (DBP) to the Neotropical electric fish Microsternarchus cf. bilineatus (Gymnotiformes)

A deltametrina é um inseticida piretróide amplamente utilizado no controle de pragas na agricultura brasileira. O uso intensivo e desordenado desse pesticida na Amazônia pode carreá-lo aos ecossistemas aquáticos de várias maneiras, mas principalmente por escoamento e lixiviação. O presente estudo foi concebido para determinar a toxicidade aguda (LC50) de um pesticida à base de deltametrina (PBD) e caracterizar seus efeitos sobre dois biomarcadores bioquímicos, a glutationa-S-transferase (GST) e a acetilcolinesterase (AChE), em tecidos do peixe elétrico Microsternarchus cf. bilineatus. Os peixes foram expostos a concentrações de 1, 2, 3, 4 e 5 µg L-1 de PBD por até 96 horas. Para cada tratamento, foi analisada a atividade absoluta das enzimas GST (músculo e fígado) e AChE (músculo e tecido nervoso). A CL50-96 h para Microsternarchus cf. bilineatus foi de 2,15 µg L-1, a menor concentração registrada para um peixe amazônico até o momento. Nenhuma das concentrações testadas deste inseticida afetou a atividade da AChE para o período de exposição testado. Um aumento significativo da atividade de GST no músculo foi detectado somente para as concentrações de 2 e 3 µg L-1. (AU)

Asma e DPOC: duas faces de um mesmo dado? / Asthma and COPD: two faces sides of the same dice?

Os imbricados processos patogênicos da asma e da doença pulmonar obstrutiva crônica (DPOC) têm mecanismos comuns que envolvem redes genéticas, subclasses de linfócitos, diversas citocinas e quimiocinas, gerando comportamento alterado de todas as células estruturais e funcionais do trato respiratório. Uma parte das centenas de genes que vêm sendo implicados na patogenia da asma e da DPOC é comum às duas. Aparentemente, eles formam uma grande rede, e sua ação conjunta está associada às alterações presentes nas duas disfunções respiratórias. Dado que parte da base genética e muitos processos inflamatórios são comuns às duas doenças, pode-se supor que elas componham uma única entidade, que pode se apresentar de diversas formas.

The overlapping pathogenic processes of asthma and chronic obstructive pulmonary disease (COPD) have common mechanisms involving genetic networks, lymphocyte subclasses, several cytokines and chemokines, generating abnormal behavior of all structural and functional cells of the respiratory tract. Part of hundreds of genes implicated in the pathogenesis of asthma and COPD are the same. Apparently, they form a large network and their joint action is associated with several changes in both respiratory disorders. As part of their genetic basis is common and many inflammatory processes are similar in both disorders, we may assume that they form a single entity that may occur in different ways.

Avaliação da atividade da enzima glutationa-s-transferase da minhoca Eisenia foetida exposta à ivermectina / Evaluation of glutatione-s-transferase enzyme activity of the earthworm Eisenia foetida exposed to ivermectin

Muitos tipos de drogas são usados na medicina veterinária para controlar e melhorar a saúde animal através de tratamentos terapêuticos e profiláticos. A desvantagem desta prática é que os produtos farmacêuticos e seus metabólitos são liberados no ambiente e podem influenciar a fauna do solo através da excreção do esterco ou pela posterior aplicação ao campo agrícola. As avermectinas são vastamente utilizadas na medicina veterinária e na agricultura. Estudos anteriores demonstraram que a ivermectina (IVM), um parasiticida amplamente utilizado, é muito tóxico para diversas espécies de invertebrados não-alvo. Tendo em vista que a IVM é pouco metabolizada, excretada de forma relativamente inalterada e pela escassez de dados sobre a toxicidade aos invertebrados do solo, foram investigados, neste estudo, os efeitos agudos e crônicos deste parasiticida sobre a glutationa-s -transferase (GST) da oligoqueta Eisenia foetida. As minhocas Eisenia foetida foram expostas à concentrações de IVM a 0, 1, 5, 10, 50 e 100 mg kg-1, e as amostras foram tomadas nos dias 7, 14 e 28 para determinação da atividade da GST. Os resultados mostraram que a duração da exposição alterou significativamente os efeitos do parasiticida investigado sobre a atividade de GST. Especificamente, após uma redução inicial, o prolongamento da exposição causou a indução da atividade da GST. Com o aumento da concentração de IVM, as atividades da GST foram inibidas significativamente após 7 dias de exposição. Em particular, o efeito inibitório foi significativo nas concentrações mais elevadas de tratamento (10, 50 e 100 mg kg-1). Por outro lado, aos 14 e 28 dias foram observadas induções na atividade da enzima. A atividade da GST pode ser considerada como parâmetro sensível para avaliar a toxicidade da ivermectina para minhocas.

Many types of drugs are used in veterinary medicine to control and improve animal health through therapeutic and prophylactic treatments. The disadvantage of this practice is that pharmaceuticals and their metabolites are released into the environment and may influence soil fauna through manure excretion and subsequent application to agricultural field. The avermectins are extensively and increasingly used in veterinary medicine and agriculture. Previous studies have shown that ivermectin (IVM), a widely used parasiticide, is very toxic to many non-target invertebrate species. In view of the little metabolism and most of the ivermectin dose given to the animal is excreted, relatively unaltered, primarily in the feces and the scarcity of data on toxicity to soil invertebrates, acute and chronic effects of the parasiticide on the glutatione-s-transferase (GST) of the oligochaete Eisenia foetida were investigated. Earthworms of Eisenia foetida were exposed to IVM at 0, 1, 5, 10, 50 and 100 mg kg-1 concentrations; samples were taken at days 7, 14, and 28 exposure for determination of GST activities. The results showed that duration of the exposure significantly changed the effects of the investigated parasiticide on the GST activity. Namely, after the initial decrease, the prolongation of exposure caused the induction of the GST activity. With increasing IVM concentration, GST activities were inhibited significantly after 7 days of the exposure. In particular, the inhibition effect was significant at the higher treatment levels (10, 50 and 100 mg kg-1). On the other hand, at 14 and 28 days were observed inductions of enzyme activity. GST activity can be regarded as sensitive parameter for evaluating the toxicity of ivermectin to earthworms.

Expressions of glutathione S-transferase P1 and 4- hydroxynonenal and the progression of prostate cancer / 中华男科学杂志

Objective@#To investigate the expressions of glutathione S-transferase (GSTP1) and tetra-hydroxynonenal (4-HNE) in prostate cancer (PCa) and their clinical significance.@*METHODS@#We determined the expressions of GSTP1 and 4-HNE in 40 patients with PCa and another 42 with benign prostatic hyperplasia (BPH) by immunohistochemistry and analyzed their relationship with Gleason grades.@*RESULTS@#The expression rate of GSTP1 was 92.9% in the BPH tissue, and those in the highly, moderately, and lowly differentiated PCa tissues were 58.3%, 20.0%, and 16.7%, respectively, significantly higher in the BPH than in the PCa group (P <0.01). However, the positive rate of 4-HNE was only 5.0% in the BPH tissue, markedly lower than 91.6%, 100.0%, and 100.0% in the highly, moderately, and lowly differentiated PCa tissues (P <0.01). There was a negative correlation between the expression of GSTP1 and that of 4-HNE in the PCa tissue (r = －2.73, P <0.01).@*CONCLUSIONS@#Expression deletion of GSTP1 and high expression of 4-HNE may play an important role in the progression of prostate cancer.

Mitochondrial control region and GSTP1 polymorphism associated with familial urinary bladder cancer in Karbi-Anglong tribe of Assam, Northeast India

Background: Multiple studies have suggested that subjects with glutathione S-transferase P1 [GSTP1]-mutations are at high risk for urinary bladder cancer [UBC]

Methods: In the present study, we evaluated the mutations in GSTP1 and mitochondrial D-loop genes in two unrelated familial bladder cancer patients belonging to Karbi Anglong Assam tribe. Mitochondrial D-loop and nuclear GSTP1 polymorphic region were amplified and sequenced for all the family members and patients. Two SNPs in the GSTP1 gene for amino acid substitutions at codons 105 [Ile-Val] and 114 [Val-Ala] were genotyped by PCR-RFLP-based methods

Results: mtDNA D-loop sequence variations were found and there were A and C insertions common at positions 235 and 309, respectively for both the families. Two sequence differences were identified in urinary bladder cancer samples in GSTP1 gene. These two heteroplasmic mutations were found at positions 11qG3037G/A and 11qC3038C/A in patient, father, mother, brother and son, but not in the sister and wife samples in family 2. The GSTP1, 105Ile >Val is most susceptible to inherited UBC risk for these ethnic families. The samples from families 1 and 2, including healthy subjects were placed in macrohaplo group L3e, except the wife [macrohaplo group F1c1a] of patient in family 1, and the wife and son [haplo group M] of the patient in family-2

Conclusion: A strong familial nuclear GSTP1 sequence variation and mitochondrial control region was observed in this study for familial urinary bladder cancer. This could afford early recognition of patients at risk of developing micro- or macroscopic, pathological lesions as well as the introduction of preventive measures for familial bladder cancer

Genotype-phenotype association of TGF-pi and GST with chemo-radiotherapy induced toxicity

Background: Normal tissue toxicity continues to remain as a major challenge for radiation oncologists for delivering the total dose to the tumour cells in cancer patients. Cellular, molecular and plasma based early biomarkers to predict the overreactions and non-overreactions of normal tissue toxicity before the initiation of radiotherapy can be valuable for personalised treatment. The aim of the current study was to analyse the interrelationship between polymorphisms in Glutathione S- Transferases [GSTs] and Transforming Growth Factor-pi [TGF-J31], the plasma level/activity of these proteins with the development of chemo-radiotherapy induced oral mucositis and skin reaction in head and neck cancer [HNC] patients

Materials and Methods: We analysed polymorphisms in TGF-fil and GST by restriction digestion of the PCR amplified products and we also assessed circulating TGF-pl levels and GST activity by Enzyme Linked Immunosorbent Assay [ELISA]

Results: The results indicate that pre-radiotherapy plasma TGF-P1 levels and total GST activity has no correlation with radiation induced normal tissue skin reaction and oral mucositis in HNC patients

Conclusion: The selected polymorphisms in TGF-fil and GST had no influence on TGF-P1 levels and total GST activity. Plasma TGF-P1 and GST activity was not affected by the presence of selected polymorphisms and lacks significance in predicting skin reaction and oral mucositis prior to chemo-radiotherapy

Glutathione S-transferase P1 Ile105Val Polymorphism and Male Infertility Risk: An Updated Meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several studies concerning the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and male infertility risk have reported controversial findings. The present study was aimed to explore this association using a meta-analysis.</p><p><b>METHODS</b>The PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched. Odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the strength of the association.</p><p><b>RESULTS</b>A total of 3282 cases and 3268 controls in nine case-control studies were included. There was no significant association between GSTP1 Ile105Val polymorphism and male infertility in the overall population, but significant associations were found under the dominant (OR = 1.23, 95% CI = 1.04-1.46, I2 = 32.2%) and heterozygote (OR = 1.29, 95% CI = 1.08-1.53, I2 = 26.8%) models after excluding studies for which the data did not satisfy Hardy-Weinberg equilibrium (HWE). Similarly, subgroup analyses revealed no significant association in Asians or Chinese population although a significant association was apparent among Chinese population in studies with HWE under the heterozygote model (OR = 1.25, 95% CI = 1.03-1.52, I2 = 44.1%). Significant heterogeneity could be observed in some genetic models, but this heterogeneity was not significant when stratified by HWE. No evidence for publication bias was found.</p><p><b>CONCLUSIONS</b>The GSTP1 Ile105Val polymorphism might not be associated with male infertility risk, and thus additional well-designed studies with larger sample size are warranted.</p>

Association of glutathione-S-transferase M1,P1, and T1 gene polymorphisms with treatment response in childhood acute lymphocytic leukemia

@#<p style="text-align: justify;">There is still a strong need for new treatment strategies that will maintain remission and prolong survival in patients with acute lymphoblastic leukemia (ALL). The glutathione-S-transferase (GST) enzymes, which are coded by highly polymorphic genes, have been associated with the risk of developing cancer and were found to regulate effect of cancer treatment drugs.<br /><strong>OBJECTIVES:</strong> The present study determines the association of GSTM1, GSTP1 and GSTT1 polymorphisms and treatment response in terms of occurrence of adverse events and relapse in ALL in Filipino children.<br /><strong>METHODS:</strong> This is a follow up study on the 2007 investigation done by Alcausin et al. which determined the association of the GST P1, M1, and T1 polymorphisms and occurrence of ALL. Four-year follow-up data were available for 46 out of the 50 patients from January 2007 to May 2011. Odds ratios (OR) as measures of association of GST M1, P1 and T1 gene polymorphisms with treatment outcomes were estimated at 95% confidence interval.<br /><strong>RESULTS:</strong> Results show a trend towards predisposition to elevation of liver enzymes in patients with GSTT1 and GSTP1 mutant genotypes showing an OR (95% Cl) of 2.0 (0.62-6.49). The presence of GSTM1 null genotype showed a trend towards protection from occurrence of relapse basing on both crude and adjusted ORs, 0.58 (0.16-2.07) and 0.23 (0.05-1.20), respectively. However, these results are not statistically significant.<br /><strong>CONCLUSION: </strong>The GSTP1 heterozygous genotype conferred increased predisposition to elevation of liver enzymes while the GSTT1 null genotype was shown to be a possible risk factor towards the occurrence of both infection and elevation of liver enzymes during chemotherapy. Furthermore, the GSTM1 null genotype appears to be protective from occurrence of relapse. It is recommended to do similar large-scale studies in the future to obtain more conclusive results.</p>

Spatial and temporal biomarkers responses of Astyanax jacuhiensis (Cope, 1894)(Characiformes: Characidae) from the middle rio Uruguai, Brazil

Due to intense agricultural activity in the rio Uruguai (South Brazil), there is the potential for aquatic contamination by agrochemicals. In this region, there are many reservoirs to meet the water demand for rice fields, forming lentic environments. In line with this information, the aim of this study was to show a comparative analysis of some biomarkers, such as lipid peroxidation (TBARS), gluthatione S-transferase (GST), non-protein thiols (NPSH), amino acids (AA) and piscine micronucleus tests (MNE) in Astyanax jacuhiensis from lentic and lotic environments in the middle rio Uruguai region, comparing warm and cold seasons. Eight pesticides were found in water samples, with propoxur having the highest concentration found in both environments and seasons. Fish from the warm season showed higher levels of biochemical biomarkers, and fish from the cold season showed higher levels of MNE and AA. TBARS and AA presented higher levels in fish from the river, while GST, NPSH, MNE and AA presented higher levels in fish from dams. These environments have different characteristics in terms of redox potential, aeration, sedimentation, trophic structure, agrochemicals input and others, which may affect the physiological and biochemical responses of fish in against adverse situations.

Devido à intensa atividade agrícola no rio Uruguai (Sul do Brasil), há potencial para contaminação aquática por agrotóxicos. Há muitos reservatórios para atender a demanda de água de campos de arroz, formando ambientes lênticos. De acordo com estas informações, o objetivo do presente estudo foi mostrar uma análise comparativa de alguns biomarcadores como a peroxidação lipídica (TBARS), glutationa S-transferase (GST), tióis não-protéicos (NPSH), aminoácidos (AA) e teste písceo de micronúcleos (MNE) em Astyanaxjacuhiensis amostrados em ambientes lóticos e lênticos da região do médio rio Uruguai, comparando estações quentes e frias. Oito pesticidas foram encontrados em amostras de água, sendo propoxur a maior concentração encontrada em ambos os ambientes e estações. Peixes da estação quente apresentaram maiores níveis de biomarcadores bioquímicos e peixes da estação fria apresentaram maiores níveis de MNE e AA. TBARS e AA apresentaram maiores níveis nos peixes de rio, enquanto GST, NPSH, MNE e AA apresentaram níveis mais elevados em peixes da represa. Estes ambientes têm características diferentes, com potencial redox, aeração, sedimentação, estrutura trófica, a entrada de agroquímicos e outros que podem afetar as respostas fisiológicas e bioquímicas de peixe contra situação adversa.

Oxidative stress parameters in juvenile brazilian flounder Paralichthys orbignyanus (Valenciennes, 1839) (Pleuronectiformes: Paralichthyidae) exposed to cold and heat shocks

The aim of this study was to determine oxidative stress parameters in the liver and gill of Brazilian flounder juveniles (307.0 ± 16.0 g and 30.0 ± 4.0 cm) submitted to different water temperature (17.1, 23.0 and 28.8ºC) for 72 h and maintained at salinity 25‰. After the acclimation of 7 days, in 23ºC, fish were transferred to 200 L tanks containing seawater (salinity 25‰) at 28.8ºC (heat shock), 17.1ºC (cold shock) or 23.0ºC (control), five replicates (five fish tank-1). The sampled collection occurred in 0 (pre-challenge), 3, 24, 48 and 72 h after temperature shock. Flounder exposed to 17.1ºC and 28.8ºC showed significantly higher TBARS levels and GST activity in the liver post-exposition (PE) in relation to the control (23ºC). CAT activity in liver present a significantly increase at 17.1ºC, in first 48 h, and subsequently decrease in 72 h PE in relation to 28.8ºC. The gills of flounder showed significantly higher TBARS levels, GST and CAT activity when submitted at 17.1 and 28.8ºC in relation to 23.0ºC. There were observed changes in lipid peroxidation levels (LPO), CAT and GST activities in the liver and gill of Brazilian flounder in response to reactive oxygen species (ROS) produced by thermal shocks.

O objetivo deste estudo foi determinar os parâmetros de estresse oxidativo no fígado e brânquias de juvenis de linguado (307,0 ± 16,0 g e 30,0 ± 4,0 cm) submetidos a diferentes temperaturas da água (17,1, 23,0 e 28,8ºC) por 72 h e mantidos na salinidade de 25‰. Após uma aclimatação de sete dias, em 23ºC, os peixes foram transferidos para tanques de 200 L contendo água do mar (salinidade 25‰) em 28,8ºC (choque quente), 17,1ºC (choque frio) ou 23,0ºC (controle), cinco repetições (cinco peixes/tanque). A coleta de amostras ocorreu em 0 (pré-exposição), 3, 24, 48 e 72 h após o choque térmico. O linguado exposto a 17,1ºC e 28,8ºC apresentaram um significante aumento dos níveis de TBARS e atividade da GST no fígado pós-exposição (PE) em relação ao controle (23ºC). A atividade da CAT no fígado apresentou um aumento significativo em 17,1ºC, nas primeiras 48 h, e subsequente diminuição em 72 h PE em relação a 28,8ºC. As brânquias do linguado apresentaram significante aumento dos níveis de TBARS e atividade da GST e CAT quando submetidos a 17,1ºC e 28,8ºC em relação a 23,0ºC. Foram observadas alterações nos níveis de peroxidação lipídica (LPO) e atividade de GST e CAT no fígado e brânquias de linguado em resposta as espécies reativas de oxigênio (ROS) produzidas pelo choque térmico.

Unraveling Brazilian Indian population prostate good health: clinical, anthropometric and genetic features

Purpose To compare dietary, lifestyle, clinical, anthropometric, genetic and prostatic features of Brazilian Indians and non-Indians (Amazon). Methods 315 men, 228 Indians and 89 non-Indians, ≥40 years old were submitted to digital rectal examination, serum prostate specific antigen (PSA), testosterone, TP53 and GSTP1 genotyping, anthropometric, lifestyle, dietary, personal and familial medical history. Prostatic symptoms were evaluated with the International Prostate Symptom Score (IPSS). Results Macuxis and Yanomamis represented 43.6% and 14.5% of Indians respectively who spontaneously referred no prostate symptoms. Mean IPSS was 7, range 3-19, with only 15% of moderate symptoms (score 8-19); Mean age was 54.7 years, waist circumference 86.6 cm, BMI 23.9 kg/m2. Yanomamis presented both lower BMI (21.4 versus 24.8 and 23.3, p=0,001) and prostate volume than Macuxis and “other ethnic groups” (15 versus 20, p=0.001). Testosterone (414 versus 502 and 512, p=0.207) and PSA (0.48 versus 0.6 and 0.41, p=0.349) were similar with progressive PSA increase with aging. Val/Val correlated with lower PSA (p=0.0361). Indians compared to control population presented: - TP53 super representation of Arg/Arg haplotype, 74.5% versus 42.5%, p<0.0001. -GSTP1 Ile/Ile 35.3% versus 60.9%; Ile/Val 45.9% versus 28.7%; Val/Val 18.8% versus 10.3%; p=0.0003. Conclusions Observed specific dietary, lifestyle, anthropometric and genetic profile for TP53 and GSTP1 may contribute to Brazilian Indian population prostate good health. .

Association of SPO11 and GST gene polymorphisms with idiopathic male infertility in ethnic Han Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the possible roles of polymorphisms of SPO11 and glutathionine S-transferase (GST) genes in idiopathic male infertility in a ethnic Han Chinese population from Henan.</p><p><b>METHODS</b>Multiplex PCR and DNA sequencing were performed to determine the SPO11 c.517C>T(rs28368082) and GST genes (GSTM1, GSTT1, GSTP1) polymorphisms in 216 idiopathic male infertility cases and 198 normal samples.</p><p><b>RESULTS</b>The frequencies of the SPO11 CC and CT genotypes were 87.5% (189/216) and 12.5% (27/216) in the patients, and 97.5% (193/198) and 2.5% (5/198) in the controls, respectively. The frequencies of SPO11 CC and CT genotypes, the A>G transition at nucleotide 313 in the exon 5 of the GSTP1 gene, and the frequencies of combined genotypes GSTM1 (-/-), GSTT1 (+/+), GSTP1 (AA) and SPO11 (CT) were significantly different between the two groups (P<0.05).</p><p><b>CONCLUSION</b>The rs28368082 polymorphism of the SPO11 gene, the A>G transition at nucleotide 313 in the exon 5 of the GSTP1 gene, and the combined genotypes of GSTM1 (-/-), GSTT1 (+/+), GSTP1 (AA) and SPO11 (CT) may be associated with idiopathic male infertility in ethnic Han Chinese.</p>

Human glutathione S-transferase polymorphisms associated with prostate cancer in the Brazilian population

Objective To evaluate the influence of polymorphisms in GSTA1, GSTM1, GSTT1, and GSTP1 in the risk of developing Prostate Cancer (PCa) in a population of Rio de Janeiro and compare the distribution of allele and genotype frequencies of the polymorphisms analyzed in the present study population with other regions in the country and different ethnic groups. Materials and Methods We analyzed a sample of the Brazilian population, comprising 196 patients with PCa treated by the urology services of the Brazilian National Cancer Institute (INCA) and Mario Kroeff Hospital (HMK), and 208 male blood donors from the Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro (UFRJ). The polymorphisms were determined in DNA, extracted from peripheral blood leucocytes using the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP). Results Our results showed that the distribution of polymorphisms can vary significantly according to the Brazilian region and ethnic groups. The distribution of allele and genotype frequencies of the polymorphism GSTA1 was statistically different between cases and controls. Genotypes (A / B + B / B) were associated with protection (OR = 0.61, 95 % CI = 0.40-0.92) for PCa in comparison to genotype A / A. Conclusion The distribution of genotype frequencies of the polymorphism GSTA1 was statistically different between the case and control groups (p = 0.023), and the presence of genotypes A / B and B / B suggests a protective role against the risk of PCa compared to genotype A / A. This is the first study that reports the genotypic frequency of this polymorphism and its association with PCa in a Brazilian population sample. .

Expression of human glutathione S-transferase A1, P1 and T1 in Escherichia coli / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To construct the vectors of human glutathione S-transferase A1 (GSTA1), P1 (GSTP1), T1(GSTT1) genes and express in Escherichia coli (E. coli).</p><p><b>METHODS</b>Human GSTA1, GSTP1 and GSTT1 gene whole length cDNAs were amplified by RT-PCR and then subcloned into pET-28a(+) vectors. The proteins were expressed in E. coli BL21(DE3). After purified by Ni2+ affinity chromatography, the enzymatic activities of GSTs were measured with 1-chloro-2,4 -dinitrobenzene (CDNB) as substrate.</p><p><b>RESULTS</b>The correct GSTA1, GSTP1 and GSTT1 genes were cloned. And soluble GSTA1, GSTT1, GSTP1 proteins were expressed in E.coli. After purification, GSTA1, GSTT1 and GSTP1 showed good enzymatic activities, which were 17.55, 0.02, 18.75 μmol·min-1·mg-1, respectively.</p><p><b>CONCLUSION</b>The expression plasmids for GSTA1, GSTT1 and GSTP1 have been constructed and the recombinant proteins are expressed successfully.</p>

Glutathione-S-transferase [GSTPL] gene polymorphism and susceptibility to hepatocellular carcinoma in Egypt

Hepatocellular carcinoma [HCC] is one of most frequent cancer in the world, genetic polymorphisms have been reported to play a role in susceptibility to HCC. The present study aimed to study the possible association between glutathione - S - transferase [GSTP] gene polymorphism and susceptibility to HCC. The study was carried out on 120 subjects divided into 3 groups: Group [A] included 60 HCC patients and group [B] included 40 chronic hepatitis C virus patients and group [C] included 20 age and sex matched healthy control. All subjects were submitted to full history taking, liver function tests, GSTPl gene polymorphism by PCR - RFLP. This study found a significant difference between HCC group and each of hepatitis C virus group [HCV] and control group, while there is no significant differences between HCV group and the control group as regarding GSTPl genotyping with the highest percent of ile/val polymorphism [IV] and val/val polymorphism [W] in HCC group and ile/ile [II] polymorphism among HCV and the control group. GSTPl IV genotype frequency was associated with 5.53 times higher risk of HCC than GSTPl II genotype, while GSTPl VV genotype frequency was associated with 6.40 times higher risk of HCC than GSTPl II genotype when compared to the other two groups together. The frequency of GSTPl val [V] allele is higher in HCC when compared to the other two groups together and it was associated with 2.70 timeshigher risk of HCC than GSTP1 I allele. The present study reported that carriage of GSTP1 ile/val and val/val genotypes have a role in susceptibility to HCC and this susceptibility are not through the alteration of the expression of clinical pathological markers and we recommend performance of this work on a large scale to confirm these results

Association between Glutathione S-Transferase T1, M1, and P1 Genotypes and the Risk of Colorectal Cancer

Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 null genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P(heterozygous)=0.790 or P(variant)=0.261). Furthermore, individuals who simultaneously carried the null genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.

Exposure to pesticides and heterozygote genotype of GSTP1-Alw26I are associated to Parkinson's disease / Exposição a pesticidas e genótipo heterozigoto de GSTP1-Alw26I associam-se à doença de Parkinson

Objective This study aimed to analyze the frequency of GSTP1-Alw26I polymorphism and to estimate its association with toxic substances in Parkinson's disease (PD). Methods A study group with 154 patients - subdivided into familial and sporadic PD groups - and 158 elderly individuals without the disease (control group) were evaluated. GSTP1-Alw26I polymorphism was analyzed by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Results Patients were significantly more exposed to pesticides compared with the control group (p=0.0004), and the heterozygote genotype associated to exposure to pesticides also prevailed in patients (p=0.0001). Wild homozygote genotype was related to tobacco use (p=0.043) and alcoholism (p=0.033) in familial PD patients. Conclusion Exposure to pesticides is associated to PD, whose effect can be enhanced when combined with the heterozygote genotype of GSTP1-Alw26I. Also, large genetic and environmental studies considering tobacco use, alcoholism, GSTP1 and PD are necessary to confirm our findings. .

Objetivo Analisar a frequência do polimorfismo GSTP1-Alw26I, assim como estimar sua associação com substâncias tóxicas na doença de Parkinson (DP). Métodos A casuística avaliada foi composta por um grupo de estudo, com 154 pacientes, subdivididos em DP familial e esporádica, e outro com 158 idosos sem a doença (grupo controle). O polimorfismo GSTP1-Alw26I foi analisado por reação em cadeia da polimerase/polimorfismo de comprimento do fragmento de restrição (PCR/RFLP). Resultados Os pacientes foram significativamente mais expostos a pesticidas, comparados com o grupo controle (p=0,0004), e o genótipo heterozigoto associado a exposição a pesticidas também prevaleceu nos pacientes (p=0,0001). O genótipo homozigoto selvagem apresentou relação com tabagismo (p=0,043) e etilismo (p=0,033) em pacientes com DP familial. Desse modo, a exposição a pesticidas está associada à DP, cujo efeito pode ser potencializado quando combinado ao genótipo heterozigoto de GSTP1-Alw26I. Estudos genético-ambientais envolvendo tabagismo, etilismo, GSTP1 e DP devem ser realizados em casuísticas numerosas, confirmando essa associação. .