ABSTRACT
Background: Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease globally. Oxidative stress which is classically defined as an event resulting from the magnitude of imbalance between oxidant and antioxidant substances, generated in a setting of oxidation-reduction reactions, and is hypothesized to play a role in the development of diabetic nephropathy. Aim and Objectives: The aim of the study was to assess lipid peroxidation by estimating serum malondialdehyde (MDA) and antioxidant status by assaying paraoxonase-1 (PON-1) in diabetes patients with nephropathy and healthy controls. Furthermore, the study aimed the correlation between MDA and PON-1 levels in patients with diabetic nephropathy. Materials and Methods: A cross-sectional comparative study was conducted in 152 participants, which were divided into two groups as control (n = 76) non-diabetic, healthy, age-, and sex-matched individuals and diabetic patients with nephropathy(n = 76). The study was conducted in Government Medical College, Kozhikode. All the subjects who satisfied the inclusion and exclusion criteria and who gave informed consent were included in a consecutive manner till sample size is achieved. Serum MDA and PON-1 were estimated using spectrophotometry. The data were analyzed using statistical package for the social sciences (SPSS) version 18. Results: Oxidative stress was increased in diabetic nephropathy patients as evidenced by significantly elevated MDA and reduced PON-1 than the normal controls. There was a significant negative correlation of serum MDA with serum PON-1 in patients with diabetic nephropathy. Conclusion: Oxidative stress is an important pathophysiological process for the development of diabetic nephropathy. This study reveals the importance of screening all diabetes patients for oxidative stress. Dietary management and antioxidant supplementation would help them to prevent development of diabetic nephropathy and related complications, which, in turn, improve their quality of life.
ABSTRACT
Abstract Objective The aim of the present study was to examine the relation between the PON1 polymorphisms and recurrent pregnancy loss (RPL). Methods In a cross-sectional study, blood samples were collected from 100 females. DNA was extracted and PON1 genotypes were determined by polymerase chain reaction (PCR) amplification. Results Regarding PON1 L55M, the mutated allele (M) frequency was found in 70.5% in RPL and in 53.5% in controls; theMallele was significantly associated with an increased risk of RPL (adjusted odds ratio [ORadj]=2.07; 95% confidence interval [CI]; p<0.001). However, regarding PON1 Q192R, the R mutated allele frequency was found in 28.5% in RPL and in 33% in controls. The R allele did not show any risk for RPL (ORadj 0.81; 95%CI; p=0.329). Conclusion The present study suggests that there is an effect of genetic polymorphism on RPL and provides additional evidence that combines with the growing information about the ways in which certain PON1 genotypes can affect the development of the fetus in the uterus.
Resumo Objetivo O objetivo deste estudo foi examinar a relação entre os polimorfismos PON1 e perda recorrente de gravidez PRG. Métodos Em um estudo transversal, foramcoletadas amostras de sangue de 100 mulheres. O DNA foi extraído e os genótipos PON1 foram determinados por amplificação por PCR. Resultados Com relação ao PON1 L55M, a frequência do alelo mutado (M) foi encontrada em 70,5% no PRG e em 53,5% nos controles; o alelo M foi significativamente associado a um risco aumentado de PRG (odds radio ajustado [ORadj] =2,07; intervalo de confiança [IC] 95%; p<0,001). No entanto, em relação ao PON1 Q192R, a frequência do alelo mutado R foi encontrada em 28,5% no PRG e em 33% nos controles. O alelo R não mostrou qualquer risco para PRG (ORadj 0,81; IC 95; p=0,329). Conclusão O presente estudo sugere que há um efeito do polimorfismo genético sobre PRG e fornece evidências adicionais que se combinam com as informações crescentes sobre asmaneiras pelas quais certos genótipos PON1 podemafetar o desenvolvimento do feto no útero.
Subject(s)
Humans , Female , Pesticides , Abortion, Habitual/genetics , Polymorphism, Genetic , Cross-Sectional Studies , Aryldialkylphosphatase/geneticsABSTRACT
ABSTRACT Purpose: Paraoxonase-1 activity is associated with age-related macular degeneration. Two polymorphisms (L55M and Q192R) were shown to increase paraoxonase-1 activity and have been implicated in the development of age-related macular degeneration. The results of studies that have examined these polymorphisms are conflicting, showing no effect, as well as increased or decreased risk. Therefore, this meta-analysis was conducted to determine the effect of these polymorphisms on age-related macular degeneration. Methods: PubMed, EBSCO, LILACS, and Scopus databases, as well as and the retrieved bibliographies of publications were searched for case-control studies that examined for paraoxonase-1 polymorphisms and age-related macular degeneration. Data were analyzed using the Comprehensive Meta-Analysis Version 2.2 and the NCSS Statistical Version 2020 software. Genotype distributions were extracted and, depending on the level of heterogeneity, fixed effects or random effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. Results: Overall, for the L55M polymorphism, none of the genetic models demonstrated a significant association. However, for non-Asian populations, a significant association was determined for the heterozygous and dominant genetic models (ORrange=1.24-1.27, p<0.05). For the Asian population, the heterozygous, dominant, and allelic genetic models demonstrated a benefit/protective factor (ORrange=0.29-0.35, p<0.05). For the Q192R polymorphism, none of the genetic models demonstrated a significant association. However, when the cohort was grouped by ethnicity, a significant association was determined in the Asian population for the recessive and allelic genetic models (ORrange=1.63-2.08, p<0.05). However, for the non-Asian population, there was no association observed. Also, there was no identifiable risk when the cohort was stratified into exudative and non-exudative cases. Conclusions: The paraoxonase-1L55M polymorphism increases the risk of developing age-related macular degeneration in non-Asian populations, whereas in Asian populations, the polymorphism exerts a protective effect. However, for the paraoxonase-1 Q192R polymorphism, only the Asian population demonstrated a risk of developing age-related macular degeneration.(AU)
RESUMO Objetivo: A atividade da paraoxonase1 está associada à degeneração macular relacionada à idade. Dois polimorfismos (L55M e Q192R) mostraram aumentar a atividade da paraoxonase1 e foram implicados no desenvolvimento da degeneração macular relacionada à idade. Os estudos que examinaram esses polimorfismos apresentaram resultados conflitantes: nenhum efeito, risco aumentado ou diminuído. Assim, esta meta-análise foi realizada para determinar o efeito desses polimorfismos na degeneração macular relacionada à idade. Métodos: Foi feita uma busca nos bancos de dados PubMed, EBSCO, LILACS e SCOPUS, bem como nas bibliografias compiladas das publicações, buscando-se estudos caso-controle que tivessem analisado os polimorfismos da paraoxonase1 e a degeneração macular relacionada à idade. Os dados foram analisados com software Comprehensive Meta-Analysis, versão 2.2, e NCSS Statistical, versão 2020. As distribuições de genótipos foram extraídas e, dependendo do nível de heterogeneidade, modelos de efeitos fixos ou aleatórios foram utilizados para calcular razões de probabilidade (RPs) combinadas, com intervalos de confiança de 95% (IC 95%) para os modelos genéticos heterozigoto, homozigoto, dominante, recessivo e alélico. Resultados: Em geral, nenhum dos modelos genéticos demonstrou associação significativa para o polimorfismo L55M. Entretanto, em populações não asiáticas, foi determinada uma associação significativa para os modelos genéticos heterozigoto e dominante (RPfaixa=1,24-1,27, p<0,05). Para a população asiática, os modelos heterozigoto, dominante e alélico mostraram um fator benéfico ou protetor (RPfaixa=0,29-0,35, p<0,05). Para o polimorfismo Q192R, nenhum dos modelos genéticos demonstrou qualquer associação significativa. Porém, quando a coorte foi agrupada por etnia, determinou-se uma associação significativa na população asiática para os modelos genéticos recessivo e alélico (RPfaixa=1,63-2,08, p<0,05). Contudo, nenhuma associação foi observada para a população não asiática. Não houve risco identificável quando a coorte foi estratificada em exsudativa e não exsudativa. Conclusões: Determinamos que o polimorfismo L55M da paraoxonase1 de fato aumenta o risco de desenvolvimento de degeneração macular relacionada à idade em populações não asiáticas, enquanto que em populações asiáticas, esse polimorfismo tem um efeito protetor. Porém, para o polimorfismo Q192R da paraoxonase1, apenas a população asiática demonstrou risco de desenvolver degeneração macular relacionada à idade.(AU)
Subject(s)
Humans , Polymorphism, Genetic , Aryldialkylphosphatase , Macular Degeneration/etiology , EthnicityABSTRACT
Objective: Paraoxonase 1 (PON1) plays a defensive role against oxidative stress by destroying oxidized lipids. Q192R single nucleotide polymorphism of PON1 gene alters the enzyme's activity. Several investigations reported a link between Q192R and an increased risk of developing tumors including uterine leiomyomas. We assessed the antioxidant effects of Q192R on myoma which fluctuate in frequency between populations. Study Design: The cohort consisted of 68 unrelated uterine leiomyoma patients and 93 healthy controls that were randomly selected from women with no ultrasonographic evidence of myoma. Materials and Methods: Genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction. Chi-square test was selected to evaluate differences between the groups. Results: To analyze the correlation between PON1 Q192R and leiomyoma risk, the AA genotype was given as a reference genotype then the two other genotypes were compared with the reference. A significantly (P < 0.05) increased risk of myoma was observed with both Q192R homozygote GG and heterozygote AG genotypes. The odds ratio (OR) of AG genotype was calculated 1.8 (confidence interval [CI]: 0.94–3.62). A higher OR was seen with GG genotype (OR: 2.8; 95% CI: 0.98–8.18). Conclusion: Oxidative stress has been suspected of having a link with tumor development, and the role of endogenous-free radical scavenger is taken into consideration. Increased protein oxidative stress status and reduced antioxidant capacity have been observed in leiomyomas patients. Our study indicates that the low-antioxidant PON1 R192 allele correlates to leiomyoma development
ABSTRACT
Abstract Objective: The cardioprotective enzyme paraoxonase-1 (PON1) suffers an important influence from genetic polymorphisms and nutritional factors. The aim of this study was to investigate the influence of diet, nutritional status, and the C(-107)T polymorphism on PON1 arylesterase activity in children. Methods: This was a cross-sectional study with 97 children, aged between 5 and 8 years, of both genders, from a pediatric outpatient clinic in southern Brazil. A sociodemographic, behavioral, and food consumption questionnaire was applied, and anthropometric measurements and laboratory blood samples were taken. PON1 arylesterase activity was measured by phenol extinction (U/mL), and DNA extraction and analysis of the PON1 C(-107)T polymorphism were performed. The Hardy-Weinberg equilibrium was tested with the chi-squared test and linear regression was used to estimate PON1 activity according to four adjustment models, with an acceptable error of 5%. Results: In the sample, the male gender accounted for 50.5%, 39.2% were 6 years of age, 54.5% had normal weight, and 51.5% had PON1 activity below the median (90.0, 15-30 U/mL). Genotype frequency was 54.6% (53/97), 31.0% (30/97), and 14.4% (14/97), respectively, for CT, CC, and TT, consistent with the Hardy-Weinberg equilibrium (p = 0.22). In the regression analysis, the model that included sociodemographic variables as well as frequency of consumption of fruits, vegetables, legumes, dairy products, and beans estimated a variability of 14.8% in PON1 activity combined with the PON1 C(-107)T polymorphism. Conclusions: During childhood, a good-quality diet with greater inclusion of healthy foods was important to predict the activity of the cardioprotective enzyme PON1 combined with the C(-107)T polymorphism of the PON1 gene.
Resumo Objetivo: A enzima cardioprotetora Paraoxonase 1 (PON1) sofre importante influência de polimorfismos genéticos e fatores nutricionais. O objetivo deste estudo foi investigar a influência da alimentação, do estado nutricional e do polimorfismo C(-107)T sobre a atividade arilesterase da PON1 em crianças. Métodos: Estudo transversal com 97 crianças entre 5 e 8 anos, de ambos os sexos, de um ambulatório de pediatria no sul do Brasil. Realizou-se questionário sociodemográfico, de comportamento e de consumo alimentar, medidas antropométricas e coleta de sangue em laboratório. A atividade arilesterase da PON1 foi mensurada pela extinção de fenol (U/mL), realizada extração do DNA e análise do polimorfismo PON1 C(-107)T. O equilíbrio de Hardy-Weinberg foi testado com qui-quadrado e usada regressão linear para estimar a atividade da PON1 segundo quatro modelos de ajuste, erro aceitável de 5%. Resultados: Na amostra o sexo masculino representou 50,5%, 39,2% tinham 6 anos, 54,5% eram eutróficos e 51,5% tinha atividade da PON1 inferior à mediana (90,0;15-30 U/ml). A frequência dos genótipos foi 54,6% (53/97), 31,0% (30/97) e 14,4% (14/97), respectivamente, para CT, CC e TT, estiveram em equilíbrio de Hardy-Weinberg (p = 0,22). Na análise de regressão o modelo que incluiu variáveis sociodemográficas, de frequência do consumo de frutas, verduras, legumes, laticínios e feijões estimou uma variabilidade de 14,8% na atividade da PON1 combinada ao polimorfismo PON1 C(-107)T. Conclusões: Na infância uma alimentação de boa qualidade, com maior participação de alimentos saudáveis foi importante para predizer a atividade da enzima cardioprotetora PON1 combinada ao polimorfismo C(-107)T do gene da PON1.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Polymorphism, Genetic/genetics , Aryldialkylphosphatase/genetics , Brazil , Cross-Sectional Studies , GenotypeABSTRACT
Background: Diabetic peripheral sensorimotor polyneuropathy is the most common complication seen in patients with diabetes mellitus (DM). Oxidant system plays a crucial role in its physiopathology. We investigated the changes in the serum levels of total antioxidant status (TAS), total oxidant status (TOS), paraoxonase-1 (PON1) and oxidative stress index (OSI) to evaluate the antioxidant efficacy of alpha lipoic acid (ALA) and/or gabapentin in patients with diabetic polyneuropathy (DPN).Methods: Sixty-three type 2 DM patients with diabetic polyneuropathy (DPN) were enrolled in the study. Patients with DPN were divided into four groups in terms of their treatment: Group 1 consisted of treatment-naive patients; patients treated with ALA, gabapentin or combination of ALA and gabapentin comprised groups 2, 3, and 4, respectively. The patients received the medications for at least six weeks. Serum levels of TAS, TOS, PON1 and OSI were analyzed.Results: No significant difference was observed between the groups according to the oxidative stress parameters studied.Conclusions: The use of ALA and/or gabapentin in patients with DPN did not significantly affect the oxidative stress parameters, including TAS, TOS, PON1, and OSI.
ABSTRACT
Background: Birth defects are conditions of prenatal origin that are present at birth, potentially impacting an infant's health, development, and/or survival. Several environmental toxins affect the growth of the fetus during the intrauterine period by affecting various cellular components. Pesticides and industrial chemicals are known toxins that can hinder the developmental process. In this study, authors are evaluating the relation of cholinesterase and paraoxonase-1 with visible congenital anomalies.Methods: Sixty babies delivered in the labor room were selected for the study. They were divided into two groups. Thirty newborns with visible congenital anomalies were included in Group I. Only babies with visible congenital anomalies were taken as inclusion criteria for this group. This group was compared with Group II, which were taken as controls and consisted of 30 healthy newborns without any congenital anomalies. Serum cholinesterase and serum paraoxonase-1 were estimated and statistical tests were applied.Results: Serum cholinesterase and serum paraoxonase-1 were significantly low in the babies with visible congenital anomalies. Serum cholinesterase levels showed a statistically significant positive correlation with serum paraoxonase 1 level in both the groups.Conclusions: Decrease in acetylcholinesterase by various environmental toxins and the associated decrease in serum paraoxonase level imposes significant oxidant stress and the resultant risk of developing congenital anomalies.
ABSTRACT
ABSTRACT Objective Our objective in this study was to evaluate the factors predicting female sexual dysfunction (FSD) in patients with diabetes mellitus (DM). Subjects and methods The study included 149 women with DM. Sexual function was evaluated with the Female Sexual Function Index (FSFI) questionnaire, in which total scores under 26.55 characterized the occurrence of FSD (Group 1 > 26.55, Group 2 < 26.55). We recorded the patients' demographic, metabolic, and hormonal data. Ophthalmologic, neurologic, and renal complications were also evaluated. The antioxidant status of the patients in both groups was determined by measuring the activity of the enzymes paraoxonase-1 (PON-1) and arylesterase (ARE). Results Based on the FSFI scores, 60 patients were allocated to Group 1 (26.6 ± 12.3) and 89 to Group 2 (22.6 ± 9.5). Group 2 compared with Group 1 had significantly (p < 0.05) higher mean concentrations of glycated hemoglobin (HbA1c), glucose, triglycerides, and insulin, along with higher rates of metformin use, smoking, retinopathy, and nephropathy. The mean serum ARE concentrations were significantly lower in Group 2 compared with Group 1 (p = 0.000), but the mean serum PON-1 concentrations were similar between both groups (p = 0.218). On multivariable regression analysis, age, ARE activity, Beck Depression Inventory (BDI) score, and menopause were significant independent predictors of FSD (p < 0.05). Conclusions In this study, we evaluated the predictive factors determining FSD caused by DM. Despite the significant results found in our study, future randomized controlled studies with a long follow-up and a larger number of patients are required to determine how DM affects FSD.
Subject(s)
Humans , Female , Adult , Aged , Aged, 80 and over , Young Adult , Sexual Dysfunction, Physiological/etiology , Diabetes Complications , Diabetes Mellitus , Prevalence , Surveys and Questionnaires , Risk Factors , Middle AgedABSTRACT
Aims: The aim of the study was to evaluate the status and diagnostic utility of PON1.(Paraoxonase-1) Arylesterase and nitric oxide as indicator of antioxidant status in preeclampsia.Study Design:Analytical case control study.Place and Duration of Study:Sample: Department of obstretics and gynecology Department, G. M. C. Ambajogai, between July 2010 and July 2012.Methodology:We conducted a case-control study of 57 women with preeclampsia and 57 women with uncomplicated deliveries. We measured PON1 Arylesterase activity, Nitric oxide and lipid profile.Results:Serum levels of LDLc (low density lipoprotein cholesterol) are higher in cases than in controls and are statistically significant (p=0.023). However serum HDLc (high density lipoprotein cholesterol) levels are decreased significantly (p = 0.017). Serum PON1 Arylesterase showed significant decrease in cases152.68 KU/L versus controls 180.89 KU/L, p value=0.002. Serum nitric oxide also showed significant decrease in cases 22.77 ± 4.792 umol/L versus controls 25.127 umol/L, p=0.010. PON1 Arylesterase activity is found to be positively correlated with serum HDL cholesterol (r= 0.449, p value< 0.001). Multivariate logistic regression analysis was done.Conclusion:Our observed results show decrease in the antioxidant PON1 Arylesterase activity point towards their role in the pathogenesis of Preeclampsia
ABSTRACT
We were intrigued to analyze donor eyes of two individuals without retinopathy even after 40 years of type 2 diabetes mellitus. Targeted molecular factors associated with angiogenesis and the key antioxidant enzymes in retinal tissue were analyzed. Accordingly PEDF, Adiponectin and Paraoxonase 2 showed augmented mRNA expression in both the retina with no significant change in VEGF expression. Vitreous showed increased PEDF protein in donor 1 and Adiponectin in donor 2 with no change in VEGF protein. This study highlights the profile of specific molecular factors that contribute to the non-development of diabetic retinopathy changes in these individuals.
ABSTRACT
Type 2 diabetes mellitus (T2DM) is recognized as one of the most prevalent metabolic diseases, and it is mostly associated with oxidative stress, atherosclerosis and dyslipidemia. Paraoxonase 2 (PON2) due to its antioxidant properties may play a role in the atherosclerosis development. Although long-chain omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) have been shown to reduce the risk of cardiovascular disease, the exact mechanism of action is still unknown. Our goal in this study was to determine the effect of EPA administration on gene expression of PON2 in patients with T2DM. Present study was a randomized, controlled double-blind trial. Thirty-six patients with T2DM were randomly allocated to receive 2 g/day EPA (n = 18) or placebo (n = 18) for 8 weeks. There were no significant differences between 2 groups concerning demographic or biochemical variables, and dietary intakes as well (p > 0.05). However, patients received EPA showed a significant increase in the gene expression of PON2 compared with placebo group (p = 0.027). In addition, high-density lipoprotein cholesterol increased and fasting blood sugar decreased significantly after EPA supplementation compared with control group. Taken together, supplementation with 2 g/day EPA could be atheroprotective via the upregulation of PON2 in patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03258840
Subject(s)
Humans , Aryldialkylphosphatase , Atherosclerosis , Blood Glucose , Cardiovascular Diseases , Cholesterol , Diabetes Mellitus, Type 2 , Dyslipidemias , Eicosapentaenoic Acid , Fasting , Fatty Acids, Unsaturated , Gene Expression , Lipoproteins , Metabolic Diseases , Oxidative Stress , Up-RegulationABSTRACT
Objective@#To explore the prognostic value of serum paraoxonase-1(PON-1) in patients with non-muscle-invasive bladder cancer.@*Methods@#Serum levels of paraoxonase-1 (PON-1) in one hundred and twenty non-muscle-invasive bladder cancer patients (bladder cancer group) and fifty healthy controls (healthy control group) in Hankou Hospital of Wuhan were detected using spectrophotometric rate assay with p-nitrophenol as the substrate. The overall survival and disease-free survival curve was drawn by Kaplan-Meier method in different serum PON-1 levels, and independent prognostic factors were analyzed by Cox proportional hazards model.@*Results@#The serum levels of PON-1 in bladder cancer group was (116.52 ± 21.91) U/L, in healthy control group was (237.96 ± 46.97) U/L, and there was significant difference (t=23.004, P < 0.01). The patients in bladder cancer group were divided into high PON-1 group (≥ 116.52 U/L, 64 patients) and low PON-1 group (< 116.52 U/L, 56 patients) by the median of PON-1(116.52 U/L). Serum PON-1 levels were closely correlated with age of bladder cancer patients (P < 0.05), but not correlated with gender, Karnofsky score, anesthesia risk grading(ASA grade), tumor multiplicity, T stage, pathological grade and tumor size (P > 0.05). The median over-all survival time of the high PON-1 group was 62 months, and 52 months in the low PON-1 group, and there was significant difference (Log-rank=7.004, P=0.008). The median disease-free survival time of the high PON-1 group was 57 months, and 49 months in the low PON-1 group, and there was significant difference (Log-rank=4.068, P=0.044). Cox multivariate regression analysis showed that T stage, serum PON-1 levels was independently associated with overall survival and disease-free survival of patients with non-muscle invasive bladder cancer (P < 0.05).@*Conclusions@#Serum PON-1 levels is increased in non-muscle invasive bladder cancer patients, and PON-1 is an independent prognostic indicator of overall survival and disease-free survival in patients with bladder cancer.
ABSTRACT
Objective To explore the prognostic value of serum paraoxonase-1(PON-1) in patients with non-muscle-invasive bladder cancer. Methods Serum levels of paraoxonase-1 (PON-1) in one hundred and twenty non-muscle-invasive bladder cancer patients (bladder cancer group) and fifty healthy controls (healthy control group) in Hankou Hospital of Wuhan were detected using spectrophotometric rate assay with p-nitrophenol as the substrate. The overall survival and disease-free survival curve was drawn by Kaplan-Meier method in different serum PON-1 levels, and independent prognostic factors were analyzed by Cox proportional hazards model. Results The serum levels of PON-1 in bladder cancer group was (116.52 ± 21.91) U/L, in healthy control group was (237.96 ± 46.97) U/L, and there was significant difference (ti23.004, P < 0.01). The patients in bladder cancer group were divided into high PON-1 group ( ≥116.52 U/L, 64 patients) and low PON-1 group (< 116.52 U/L, 56 patients) by the median of PON-1(116.52 U/L). Serum PON-1 levels were closely correlated with age of bladder cancer patients (P < 0.05), but not correlated with gender, Karnofsky score, anesthesia risk grading( ASA grade), tumor multiplicity, T stage, pathological grade and tumor size (P > 0.05). The median over-all survival time of the high PON-1 group was 62 months, and 52 months in the low PON-1 group, and there was significant difference (Log-ranki7.004, Pi0.008). The median disease-free survival time of the high PON-1 group was 57 months, and 49 months in the low PON-1 group, and there was significant difference (Log-ranki4.068, Pi0.044). Cox multivariate regression analysis showed that T stage, serum PON-1 levels was independently associated with overall survival and disease-free survival of patients with non-muscle invasive bladder cancer (P < 0.05). Conclusions Serum PON-1 levels is increased in non-muscle invasive bladder cancer patients, and PON-1 is an independent prognostic indicator of overall survival and disease-free survival in patients with bladder cancer.
ABSTRACT
Objective@#To investigate the effects of miRNA on the expression of paraoxonase 1 (PON1) and its clinical application in the patients with nonalcoholic steatohepatitis (NASH). @*Methods@#Bioinformatics methods were used to analyze and predict PON1 related regulation on miRNA. PON1 luciferase reporter gene vectors were constructed and the activity of dual luciferase was analyzed. The up/down-regulated levels of miRNA in HepG2 cells of different groups were detected by real-time fluorescence quantitative PCR (qRT-PCR), and the levels of PON1 protein in HepG2 cells were detected by western blot. The levels of miR140-5p in the serum of healthy people and NASH patients were also analyzed by qRT-PCR. @*Results@#According to the prediction of TargetScan database, miR140-5p may bind complementarily to the end of PON13′-UTR. The analysis for the activity of dual luciferase reporter gene showed that miR-140-5p mimic significantly downregulated the fluorescence of wild type PON1 vector (P＜0.01). The results of qRT-PCR demonstrated that miR-140-5p mimic group showed high overexpression (P＜0.01) compared with the normal cell control group and the negative mimic control group, while miR-140-5p inhibitor group appeared corresponding low expression (P＜0.05). western blot results suggested that the transfection of miR140-5p mimic significantly down-regulated the expression of PON1 (P＜0.01) while miR140-5p inhibitor up-regulated this expression (P＜0.01). Compared with the healthy control group, the level of miR140-5p was decreased in the serum of NASH patients, and the difference was statistically significant (P＜0.01). @*Conclusion@#miR140-5p may be involved in the progression of nonalcoholic steatohepatitis through regulation for the posttranscriptional gene expression of PON1.
ABSTRACT
Objective: To investigate whether paraoxonase 1 (PON1) genotypes were effect modifiers in the relationship between exposure to organophosphate pesticides (OPs) and oxidative stress level in pregnant women. Methods: A total of 204 pregnant women recruited from a hospital in Shandong Province were included in the study. Four nonspecific dialkyl phosphate (DAP) metabolites of OPs were measured in each urine sample. Levels of two oxidative stress biomarkers [total free sulfhydryl (-SH) and malondialdehyde (MDA)] were measured in serum samples. Blood samples were also analyzed for detecting PON1 genotypes (PON1-108, PON1192 and PON155). Separate linear regression models were conducted to explore the relationship between DAP metabolite levels and oxidative stress levels in all 204 pregnant women or women within each PON1 genotype. Results: There was no significant association between DAP metabolite levels and oxidative stress levels in all 204 women. Levels of dimethyl phosphates [β (95% CI): -104.10 (-191.31, -16.88)] and dialkyl phosphates [β (95% CI): -111.78 (-221.84, -1.72)] were negatively associated with -SH level among pregnant women with PON1192RR genotype, but this association was not found among women with other genotypes. Conclusion: OP exposure may be associated with a higher oxidative stress level among pregnant women with PON1192RR genotype.
ABSTRACT
Objective:To investigate the effect of Cannabis sativa extract on the development of neuro- and hepato-toxicity caused by malathion injection in rats.Methods:The extract of Cannabis sativa was obtained from the plant resin by chloroform treatment. Δ-Tetrahydrocannabinol content of the extract (20%) was quantified using gas chromatography–mass spectrometry. The doses of cannabis extract were expressed as Δ -tetrahydrocannabinol content of 10 or 20 mg/kg. Malathion (150 mg/kg) was intraperitoneally administered followed after 30 min by the cannabis extract (10 or 20 mg/kg, subcutaneously). Rats were euthanized 4 h later. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide and paraoxonase-1 (PON-1) activity were determined in brain and liver. Brain 5-lipoxygenase and butyrylcholinesterase (BChE) activity were measured as well. Histopathological examination of brain and liver tissue was also performed.Results:Compared to controls, malathion resulted in increased oxidative stress in brain and liver. MDA and nitric oxide concentrations were significantly increased (P<0.05) and GSH significantly decreased with respect to control levels (P<0.05). Malathion also significantly inhibited PON-1 and BChE activities but had no effect on brain 5-lipoxygenase. Brain MDA concentrations were not altered by cannabis treatment. Cannabis at 20 mg/kg, however, caused significant increase in nitric oxide and restored the GSH and PON-1 activity. Brain BChE activity significantly decreased by 26.1% (P<0.05) after treatment with 10 mg/kg cannabis. Cannabis showed no effect on brain 5-lipoxygenase. On the other hand, rats treated with cannabis exhibited significantly higher levels of liver MDA, nitric oxide and PON-1 activity compared with the malathion control group. Rats treated with only malathion exhibited spongiform changes, neuronal damage in the cerebral cortex and degeneration of some Purkinje cells in the cerebellum. There were also hepatic vacuolar degeneration and dilated and congested portal vein. These histopthological changes induced by malathion in brain and liver were reduced to great extent by cannabis administration at 20 mg/kg.Conclusions:Our data suggest that acute treatment with cannabis alleviates the malathion-induced brain and hepatic injury in rats possibly by maintaining the levels of GSH and PON-1 activity.
ABSTRACT
Objective:To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats.Methods:Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of 10, 100 or 1 000 μ g/kg. Rats were evaluated for brain lipid peroxidation (malondialdehyde: MDA), reduced glutathione (GSH), nitric oxide (NO) levels, and paraoxonase-1 (PON-1) activity. The concentrations of the anti-apoptotic protein B cell/lymphoma-2 (Bcl-2) were determined in the striatum. Histopathologic examination and the expression of inducible nitric oxide synthase (iNOS) in the cerebral cortex and striatum were also performed.Results:Compared with the vehicle-treated group, rotenone caused a significant increase in brain lipid proxidation (MDA) by 61% (P<0.05) accompanied by an increase in NO by 73.1% (P<0.05) and a decrease in GSH concentration by 29.4% (P<0.05). In addition, brain PON-1 activity significantly decreased by 63.0% (P<0.05) and striatal Bcl-2 significantly decreased by 27.9% (P<0.05) with respect to the corresponding control value. Brain sections from rotenone treated rats showed extensive dark pyknotic and apoptotic nuclei in neurons, shrunken cytoplasm and perineuronal vacuolation. Rotenone also caused pronounced expression of iNOS in the cerebral cortex and striatum. Treatment with misoprostol at doses of 100 and 1 000 μ g/kg resulted in decreased brain MDA (by 16.5%-23.0%) (P<0.05) and NO levels (by 37.1%-40.7%) (P<0.05) and increased GSH concentrations (by 18.8%-30.1%) (P<0.05). PON-1 activity was significantly increased by 80.0%-114.8% (P<0.05) by misoprostol at 100 and 1 000 μ g/kg, respectively. In addition, misoprostol treatment restored striatal Bcl-2 concentrations to its normal value. Misoprostol treatment resulted in markedly reduced brain injury and decreased iNOS expression in the cerebral cortex and striatum of rotenone intoxicated rats.Conclusions:These data suggest that misoprostol prevents the rotenone-induced neurodegeneration in rat brain by reducing brain oxidative stress.
ABSTRACT
Objective To observe the influence of glucose fluctuation on paraoxonase-3(PON3) and apoprotein A1(ApoA1) in T2DM patients with coronary heart disease (CHD) . Methods A total of 260 subjects were enrolled in this study and dividied into three groups :T2DM patients with CHD (T2DM +CHD group ,n=100) ,T2DM without CHD (T2DM group ,n=80) and healthy subjects(NC group ,n=80) .The serum PON3 and ApoA1 levels were measured and compared in all the three groups .The 72 h dynamic glucose monitoring (CGMS ) was adopted in T2DM + CHD group ,then according to the MAGE levels ,T2DM+ CHD group was subdivided intotertiles :the lowest tertile subgroup (2.43～3.44 mmol/L ,n=31) ,the middle tertile subgroup (3.45～4.46 mmol/L ,n=39) and the highest tertile subgroup (4.47～5.45 mmol/L ,n= 30) .Influencing factors for PON3 and ApoA1 were analyzed by multivariate linear regression analysis . Results (1)The SBP ,DBP ,FPG ,2 hPG ,HbA1c ,FIns ,ApoB ,BUN ,HOMA-IR , ApoA1 and number of smokers were higher in T2DM + CHD group than in NC group .FPG ,2 hPG ,HbA1c ,FIns and HOMA-IR were higher in T2DM+ CHD group than in T2DM group(P<0.05 or P<0.01) .LDL-C ,Lp-a and hsC-RP were higher ,and the PON3 were lower in T2DM +CHD group than in T2DM group and NC group (P< 0.05 or P< 0.01);(2)With the increase of blood glucose fluctuation range ,the levels of PON3[(0.58 ± 0.10) vs (0.44 ± 0.07) vs (0.25 ± 0.01) ng/ml]and ApoA1 [(2.33 ± 1.04) vs (2.31 ± 0.71) vs(1.05 ± 0.48)g/L]were reduced(all P=0.000);(3)Multiple linear regression analysis showed that BMI ,hsC-RP ,HOMA-IR and MAGE were influencing factors for PON3. And HbA1c ,hsC-RP and MAGE were influencing factors for ApoA1 (P<0.05 or P<0.01) . Conclusion Serum PON3 level is lower and ApoA1 level is higher in T2DM patients with CHD .Glucose fluctuation may be only an influencing factor for ApoA1 level .
ABSTRACT
Objective·To investigate whether paraoxonase 1 (PON1) genotypes were effect modifiers in the relationship between exposure to organophosphate pesticides (Ops) and oxidative stress level in pregnant women.Methods · A total of 204 pregnant women recruited from a hospital in Shandong Province were included in the study.Four nonspecific dialkyl phosphate (DAP) metabolites of Ops were measured in each urine sample.Levels of two oxidative stress biomarkers [total free sulfhydryl (-SH) and malondialdehyde (MDA)] were measured in serum samples.Blood samples were also analyzed for detecting PON1 genotypes (PONI-108,PON1192 and PON155).Separate linear regression models were conducted to explore the relationship between DAP metabolite levels and oxidative stress levels in all 204 pregnant women or women within each PON1 genotype.Results· There was no significant association between DAP metabolite levels and oxidative stress levels in all 204 women.Levels of dimethyl phosphates [β (95％ CI):-104.10 (-191.31,-16.88)] and dialkyl phosphates [f (95％ CI):-111.78 (-221.84,-1.72)] were negatively associated with-SH level among pregnant women with PON1192RR genotype,but this association was not found among women with other genotypes.Conclusion· OP exposure may be associated with a higher oxidative stress level among pregnant women with PONI192RR genotype.