ABSTRACT Objective: To study associations between polymorphisms in the angiotensin converting enzyme (ACE I/D), actinin 3 (ACTN3 R577X) and paraoxonase 1 (PON1 T(-107)C) genes and chronic diseases (diabetes and hypertension) in women. Materials and methods: Genomic DNA was extracted from saliva samples of 78 women between 18 and 59 years old used for genetic polymorphism screening. Biochemical data were collected from the medical records in Basic Health Units from Southern Brazil. Questionnaires about food consumption, physical activity level and socioeconomic status were applied. Results: The XX genotype of ACTN3 was associated with low HDL levels and high triglycerides, total cholesterol and glucose levels. Additionally, high triglycerides and LDL levels were observed in carriers of the TT genotype of PON1, and lower total cholesterol levels were associated to the CC genotype. As expected, women with diabetes/hypertense had increased body weight, BMI (p = 0.02), waist circumference (p = 0.01), body fat percentage, blood pressure (p = 0.02), cholesterol, triglycerides (p = 0.02), and blood glucose (p = 0.01), when compared to the control group. Conclusion: Both ACTN3 R577X and PON1 T(-107)C polymorphisms are associated with nutritional status and blood glucose and lipid levels in women with diabetes/hypertense. These results contribute to genetic knowledge about predisposition to obesity-related diseases. Objective ACE I/D, ID I/D , I D I/D) ACTN (ACTN RX R X PON (PON T107C TC T 107 C diabetes hypertension methods 7 5 screening Brazil consumption applied Results Additionally expected diabeteshypertense hypertense weight p 0.02, 002 0.02 0 02 0.02) 0.01, 001 0.01 01 0.01) percentage group Conclusion obesityrelated obesity related 10 00 0.0 0.

BACKGROUND: Recent evidence has linked changes in plasma lecithin-cholesterol acyltransferase (LCAT) and paraoxonase-1 (PON-1) levels with increased risk for development of premature atherosclerotic cardiovascular disease (ASCVD) in different populations. However, studies on this in Nigeria and sub-Saharan Africa are scarce. OBJECTIVE: This study assessed the association between reduced plasma LCAT and PON-1 levels and an increased risk of ASCVD, and their potential as biomarkers for ASCVD. METHODS: Atherosclerotic cardiovascular disease patients and healthy controls were randomly selected for this cross-sectional case-control study from the Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria, between March 2022 and March 2023. Plasma LCAT and PON-1 were determined by sandwich enzyme-linked immunosorbent assay, while the lipid profile was measured by spectrophotometry. RESULTS: A total of 153 ASCVD patients (mean age: 52.92 ± 10.24 years) and 50 healthy controls (mean age: 46.96 ± 11.05 years) were included in the analyses. Stastistically significant increases were observed in the mean body weight, hip circumference, waist circumference, waist-to-hip ratio, body mass index, diastolic and systolic blood pressure (all p ≤ 0.001), and pulse rate (p = 0.003) compared to the control values. Statistically significant increases were also observed in the mean plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (all p ≤ 0.001). In contrast, the mean plasma high-density lipoprotein cholesterol, LCAT, and PON-1 (p ≤ 0.001) were notably reduced compared to the control values. CONCLUSION: The present study provides supportive evidence that changes in plasma LCAT and PON-1 could predispose individuals to risk of premature ASCVD. What this study adds: Plasma LCAT and PON-1 may serve as independent markers or complement other established cardiovascular disease markers to discriminate the risk of ASCVD when it is unclear..

Abstract Background Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR). Objectives To realize a systematic literature review to determine the impact of genetic variants on AR. Methods Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included. Results The genetic variants rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2), and rs5918 (ITGB3) were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance (p< 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 and rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 and rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP), and rs662 (PON1), while these differ in real interference in AR: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1), and rs20417 (PTGS2). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences. Conclusion It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR. CVD . (CVD) acid vasoconstriction Nevertheless AR (AR) MEDLINEPubMed MEDLINE PubMed MEDLINE/PubMed Cochrane Scopus LILACS screened 29 26 criteria 2 casecontrol case included rs rs112664 ITGA2, ITGA2 ITGA , (ITGA2) rs384278 PTGS1, PTGS1 PTGS (PTGS1) rs2041 PTGS2, PTGS2 (PTGS2) rs591 ITGB3 ITGB (ITGB3 studied relevance 6 p< p (p 0.05 005 0 05 95 CI [CI] article them results rs137109 P2RY1, P2RY1 PRY P RY (P2RY1) rs104564 MDR1, MDR1 MDR (MDR1) rs105193 rs775693 PLA2G7, PLA2G7 PLAG PLA G (PLA2G7) rs207174 HO1, HO1 HO (HO1) rs113188 rs452 TBXA2R, TBXA2R TBXAR TBXA R (TBXA2R) rs43447 ALOX12, ALOX12 ALOX (ALOX12) rs931504 ALOX5AP, ALOX5AP ALOXAP AP (ALOX5AP) rs66 PON1, PON1 PON (PON1) ITGB3, rs224309 GP1BA, GP1BA GPBA GP BA (GP1BA) rs133034 PTGS2. limitations differences area Therefore (CVD (AR rs11266 (ITGA2 rs38427 (PTGS1 rs204 (PTGS2 rs59 (ITGB 0.0 00 9 [CI rs13710 P2RY (P2RY1 rs10456 (MDR1 rs10519 rs77569 PLA2G (PLA2G7 rs20717 (HO1 rs11318 rs45 (TBXA2R rs4344 ALOX1 (ALOX12 rs93150 (ALOX5AP rs6 (PON1 rs22430 (GP1BA rs13303 rs1126 (ITGA rs3842 (PTGS rs20 rs5 0. rs1371 (P2RY rs1045 (MDR rs1051 rs7756 (PLA2G rs2071 (HO rs1131 rs4 rs434 (ALOX1 rs9315 (PON rs2243 rs1330 rs112 rs384 rs2 rs137 rs104 rs105 rs775 rs207 rs113 rs43 (ALOX rs931 rs224 rs133 rs11 rs38 rs13 rs10 rs77 rs93 rs22 rs1 rs3 rs7 rs9

Resumo Antecedentes A farmacogenética promete melhorar o controle de doenças como as cardiovasculares. O ácido acetilsalicílico, a aspirina, previne a formação de um agente ativador da agregação plaquetária e vasoconstrição e é usado na prevenção de tais doenças. No entanto, os pacientes podem ter falha no tratamento devido a variantes genéticas que modificam o metabolismo da droga causando resistência à aspirina (RA). Objetivos Realizar uma revisão sistemática da literatura para determinar o impacto das variantes genéticas na resistência à aspirina. Métodos Artigos publicados nos bancos de dados MEDLINE/PubMed, Cochrane, Scopus, LILACS e SCIELO foram sistematicamente selecionados. Foram identificados 290 artigos e, destes, 269 artigos foram excluídos por não atenderem aos critérios de inclusão previamente estabelecidos. Um total de 20 estudos caso-controles e 1 coorte foi incluído. Resultados As variantes genéticas rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2) e rs5918 (ITGB3) foram as mais estudadas. Quanto à relevância, das 64 variantes genéticas avaliadas pelos artigos, 14 tiveram significância estatística (p< 0,05; intervalo de confiança [IC] de 95%) em pelo menos um artigo. Entre eles, os seguintes tiveram resultados unânimes: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 e rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 e rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP) e rs662 (PON1), enquanto estes diferiram na interferência real na RA: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1) e rs20417 (PTGS2). Como limitações do estudo, destacam-se as metodologias não uniformes dos artigos analisados e as diferenças populacionais. Conclusão Vale ressaltar que a farmacogenética é uma área em expansão. Portanto, mais estudos são necessários para entender melhor a associação entre variantes genéticas e RA. cardiovasculares acetilsalicílico entanto RA . (RA) MEDLINEPubMed MEDLINE PubMed MEDLINE/PubMed Cochrane Scopus selecionados 29 destes 26 estabelecidos 2 casocontroles caso controles incluído rs rs112664 ITGA2, ITGA2 ITGA , (ITGA2) rs384278 PTGS1, PTGS1 PTGS rs2041 PTGS2 (PTGS2 rs591 ITGB3 ITGB (ITGB3 estudadas relevância 6 p< p (p 0,05 005 0 05 IC [IC 95% 95 artigo eles unânimes rs137109 P2RY1, P2RY1 PRY P RY (P2RY1) rs104564 MDR1, MDR1 MDR (MDR1) rs105193 rs775693 PLA2G7, PLA2G7 PLAG PLA G (PLA2G7) rs207174 HO1, HO1 HO (HO1) rs113188 rs452 TBXA2R, TBXA2R TBXAR TBXA R (TBXA2R) rs43447 ALOX12, ALOX12 ALOX (ALOX12) rs931504 ALOX5AP ALOXAP AP (ALOX5AP rs66 PON1, PON1 PON (PON1) ITGB3, rs224309 GP1BA, GP1BA GPBA GP BA (GP1BA) rs133034 (PTGS1 PTGS2. estudo destacamse destacam se populacionais expansão Portanto (RA rs11266 (ITGA2 rs38427 rs204 (PTGS rs59 (ITGB 0,0 00 9 rs13710 P2RY (P2RY1 rs10456 (MDR1 rs10519 rs77569 PLA2G (PLA2G7 rs20717 (HO1 rs11318 rs45 (TBXA2R rs4344 ALOX1 (ALOX12 rs93150 rs6 (PON1 rs22430 (GP1BA rs13303 rs1126 (ITGA rs3842 rs20 rs5 0, rs1371 (P2RY rs1045 (MDR rs1051 rs7756 (PLA2G rs2071 (HO rs1131 rs4 rs434 (ALOX1 rs9315 (PON rs2243 rs1330 rs112 rs384 rs2 rs137 rs104 rs105 rs775 rs207 rs113 rs43 (ALOX rs931 rs224 rs133 rs11 rs38 rs13 rs10 rs77 rs93 rs22 rs1 rs3 rs7 rs9

Abstract This study aimed to examine the effects of exercise, intermittent fasting, and combining two methods on body weight, adipose tissue, lipids, and glucoregulator and antioxidant parameters. 90 day-old male rats were randomly divided into 5 groups of 6 rats each. The groups consist of rats with normal body weight-sedentary (C), obese-sedentary (O), obese-intermittent fasting only (IF), obese-exercise (swimming) only (E), and obese-intermittent fasting together with exercise (IFE). For 8 weeks (1. phase), 1 group was fed with standard pellets (2.7 cal/g). The other 4 groups were fed with a high-fat diet (4.496 cal/g) to develop obesity. Then for 8 weeks (2. phase), all rats feeding standard pellets were exercised and/or done intermittent fasting. There was no significant difference in body weight at the beginning of the study. The change in body weight was significantly higher in C than IFE, and E. Fasting blood glucose was higher in IF and IFE. Oxidative stress index (OSI) was lower in IF and IFE. Also, paraoxonase 1 (PON1) decreased in IFE. The fat cells' diameters of IF or E were lower than O but higher than C. The fat cell diameters of IFE were smaller than C. In conclusion, a combination of intermittent fasting and exercise in obese individuals caused reduced body weight, fat cell size, and oxidative stress. Besides, it caused increased fasting blood glucose, different effects on blood lipids, and decreased PON1. Thus intermittent fasting can be suggested by considering its positive and negative aspects and keeping it under follow-up. tissue lipids parameters 9 dayold day old each weightsedentary sedentary C, , (C) obesesedentary O, (O) obeseintermittent IF, (IF) obeseexercise swimming (swimming E, (E) . (IFE) 1. (1 phase, phase phase) 2.7 27 2 7 cal/g. calg cal/g cal g highfat high 4.496 4496 496 (4.49 obesity 2. (2 andor OSI (OSI Also PON1 PON (PON1 cells conclusion size Besides followup. followup follow up. up follow-up (C (O (IF (E (IFE ( 4.49 449 49 (4.4 (PON 4.4 44 (4. 4. (4

Abstract Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to identify gene-environment interactions associated with spontaneous PTB or its predictors. We carried out a retrospective case-control study including parental sociodemographic and obstetric data as well as newborn genetic variants of 69 preterm and 61 at term newborns born at a maternity hospital from Tucumán, Argentina, between 2005 and 2010. A data-driven Bayesian network including the main PTB predictors was created where we identified gene-environment interactions. We used logistic regressions to calculate the odds ratios and confidence intervals of the interactions. From the main PTB predictors (nine exposures and six genetic variants) we identified an interaction between low neighbourhood socioeconomic status and rs2074351 (PON1, genotype GG) variant that was associated with an increased risk of toxoplasmosis (odds ratio 12.51, confidence interval 95%: 1.71 - 91.36). The results of this exploratory study suggest that structural social disparities could influence the PTB risk by increasing the frequency of exposures that potentiate the risk associated with individual characteristics such as genetic traits. Future studies with larger sample sizes are necessary to confirm these findings. (PTB worldwide geneenvironment gene environment casecontrol case control 6 Tucumán Argentina 200 2010 datadriven driven nine rs rs207435 PON1, PON1 PON (PON1 GG 1251 12 51 12.51 95% 95 171 1 71 1.7 91.36. 9136 91.36 . 91 36 91.36) traits findings 20 201 rs20743 (PON 125 5 12.5 9 17 7 1. 913 91.3 3 2 rs2074 12. 91. rs207 rs20 rs2

Resumo Fundamento Tem sido demonstrado que um aumento dos níveis séricos de PON1 é protetor contra vários distúrbios. Foi relatado que vários polimorfismos de nucleotídeo único (SNPs, single nucleotide polymorphisms ) do gene PON1 estão associados a níveis e atividade de proteínas enzimáticas séricas. Objetivos Investigar a associação de SNPs do PON1 e atividade da paraoxonase sérica com a doença arterial coronariana (DAC). Métodos Foram estudados 601 pacientes não relacionados submetidos à angiografia coronária, incluindo aqueles com estenose >50% (N=266) e aqueles com estenose <30% (N=335). Os SNPs rs662 e rs840560 do gene da paraoxonase foram determinados utilizando o método ARMS-PCR e o SNP rs705379 foi genotipado utilizando análise de PCR-RFLP. A atividade da paraoxonase sérica foi medida utilizando paraoxon como substrato. O valor de p<0,05 foi considerado significante. Resultados A atividade da paraoxonase sérica não foi significativamente diferente entre os grupos de estudo. Após ajuste para idade, sexo, hipertensão, diabetes mellitus e dislipidemia, o genótipo GG e o modelo codominante de rs662 foram positivamente associados a uma angiografia positiva (respectivamente, OR = 2,424, IC 95% [1,123-5,233], p <0,05, OR = 1,663, IC 95% [1,086-2,547]). A atividade da paraoxonase sérica foi significativamente maior no alelo G e variante GG do polimorfismo rs662, alelo A e variante AA de rs854560 e alelo C e variante CC de rs705379. A análise de haplótipos mostrou que o haplótipo ATC foi significativamente mais prevalente no grupo com angiografia negativa. A análise entre os grupos indicou que o alelo A de rs662 foi significativamente associado à menor atividade da paraoxonase no grupo com angiografia positiva (p=0,019). Conclusões A presença do alelo G do polimorfismo de nucleotídeo único rs662 está independentemente associada ao aumento do risco de DAC.

Abstract Background It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. Objective To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). Methods A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. Results Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). Conclusions The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.

ABSTRACT Introduction: Presenilin 1 (PSEN1), catalase (CAT), glutathione-S-transferase (GST) and paraoxonase 1 (PON1) play a vital role in prediction, diagnosis and therapy of metabolic disorders. Methods: Metabolic enzyme activities and lipid peroxidation in serum of cerebrovascular diseases (CVD) and coronary artery diseases were measured by spectrophotometric methods. mRNA was isolated from leukocytes of the patient group and healthy adult patients. Quantitative gene expression of PSEN1, CAT and GST mRNA was identified by quantitative real-time polymerase chain reaction (qPCR). Results: The PSEN1, CAT and GST expression in patients showed significant differences compared to the control group. PSEN1 expression in leukocytes was significantly about twice as high as that of the control group in patients with CVD. The GST, CAT and PON1 activity showed significant differences in patient groups compared to the control group. Conclusion: The mRNA expression levels can be used as a potential biomarker in the diagnosis of atherosclerosis that occurs as a result of the metabolic disorder. In atherosclerotic patients, antioxidant status is independently related to an increased risk of cardiovascular events. Antioxidant activities and mRNA expressions may have predictive value, as well as available risk factors. Introduction PSEN , (PSEN1) CAT, (CAT) glutathioneStransferase glutathione S transferase (GST PON (PON1 prediction disorders Methods CVD (CVD methods realtime real time qPCR. qPCR . (qPCR) Results Conclusion disorder events value factors (PSEN1 (CAT (PON (qPCR (PSEN

Objective: To date, no study has investigated whether autogenous and reactive obsessive-compulsive disorder (OCD) types are different entities in terms of oxidative stress and inflammatory processes. The aim of this study is to compare them in terms of these features. Methods: The study was conducted in subjects with reactive OCD (n=19), autogenous OCD (n=14), and a control group (n=17). All participants were non-smokers. Sociodemographic data were collected and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Obsessive Beliefs Questionnaire (OBQ), and Overvalued Ideas Scale (OVIS) were administered. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), paraoxonase (PON1), total oxidant status (TOS), and total antioxidant status (TAS) were measured. Results: There were no significant differences in TAS, TOS, or oxidative stress index (OSI) between the OCD and control groups. PON1 and hs-CRP levels were higher in the OCD group, whereas IL-6 and IL-10 levels were lower. Comparison across the three groups revealed no differences in TAS, TOS, OSI, or PON1 levels; however, hs-CRP was significantly higher while IL-6 and IL-10 were significantly lower in the reactive group compared to controls. Conclusion: Our results show that, although inflammatory processes may play a role in OCD, the autogenous and reactive subtypes do not differ from each other in these respects. The classification of OCD into autogenous and reactive subtypes should be reevaluated.

Abstract Many studies have examined the association between paraoxonase 1 (PON1) -L55M polymorphisms and risk of coronary heart disease (CHD), but the results remained inconsistent. We therefore aimed to address this association by performing an updated meta-analysis in the Chinese population. The PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure were searched up to May 2020. The strength of statistical association was assessed with odds ratio (OR) and 95% confidence interval (CI). A total of eight studies with 1826 CHD cases and 1817 controls were finally included in the analysis. In the overall and subgroup analyses by control sources and geographic areas, the results showed no significant associations with CHD among all analysis models. Furthermore, we performed the analysis by including or excluding the HWE-violating studies. The results suggested that the MM genetype were significantly associated with CHD in studies not consistent with HWE under recessive and dominant models. This meta-analysis demonstrates that the PON1 -L55M polymorphism may not be associated with CHD risk in the Chinese population. Further studies with strict selection of patients and controls in different ethnic populations will be required to clarify this finding.

Abstract Some scientific evidence indicates that antioxidant-rich diets may prevent the negative effects of free radicals. In this study, we aimed to evaluate the effects of kefir consumption on paraxonase-1 (PON1) activity, total antioxidant status (TAS), total oxidant status (TOS), and serum lipid parameters in smokers and non-smokers. At baseline, PON1 activity, TAS, and high-density lipoprotein cholesterol (HDL-C) levels were lower (P<0.05, P<0.01, and P<0.05, respectively) whereas TOS, triglyceride (TG), and light-density lipoprotein cholesterol (LDL-C) levels were higher (all P<0.05) in smokers compared to non-smokers. There were no significant differences in total cholesterol (TC) levels between two groups (P>0.05). After 6-week of kefir consumption, PON1 and TAS values were significantly increased in smokers (both P<0.05) and non-smokers (P<0.05 and P<0.01, respectively). Kefir consumption did not have any significant effect on TOS, HDL-C, LDL-C, TC, and TG values both in smokers (all P>0.05) and non-smokers (all P>0.05). Regular consumption of kefir increases the PON1 activity and TAS value in both smokers and non-smokers. It can be concluded that kefir plays an important role in favor of antioxidants in the formation of antioxidant/oxidant balance in both smokers and non-smokers.

ABSTRACT Organophosphate pesticides (OP) are widely used for the control of pests and vector-borne diseases by state and national governments. However, these compounds can cause acute and chronic intoxication, and diverse factors play a relevant role in their toxicity. One such factor is paraoxonase 1 (PON1), a protein that hydrolyzes OP and protects the body from toxicity. The objective of this study was to assess the serum concentration of PON1 and its relationship with risk factors in a population of fumigators from the state of Guerrero, in Mexico. A cross-sectional study was conducted with 67 fumigators and a control group of 46 non-fumigators. A survey instrument was applied to capture the labor practices and pesticides used, and anthropometric and biochemical measurements were determined. Serum concentration of PON1 was quantified by enzyme-linked immunoassay (ELISA). The results show that most of the fumigators use carbamates (38 %) and OP (32 %) pesticides. The PON1 concentrations were 21.2 ng/mL in the fumigators vs. 18.7 ng/ml in the control group. We also found that body mass index, diabetes history, time in years that the worker reports carrying out the pesticide fumigation, the number of pesticides used, and the consumption of alcohol, vitamins and food supplements were risk factors associated with PON1 concentration shifts. It is necessary to consider the intrinsic and extrinsic factors of individuals when evaluating PON1 levels in populations exposed to pesticides.

RESUMEN Los plaguicidas organofosforados (OF) son ampliamente utilizados para el control de plagas y vectores transmisores de enfermedades por gobiernos estatales y nacionales. Sin embargo, se sabe que estos compuestos pueden causar intoxicaciones agudas y crónicas, y que diversos factores desempeñan un papel relevante en su toxicidad. Uno de ellos es la paraoxonasa 1 (PON1), una proteína que hidroliza los plaguicidas OF y protege al organismo de su toxicidad. El objetivo de este estudio fue valorar la concentración sérica de PON1 y su relación con factores de riesgo que pueden modificar la concentración de la enzima en una población de fumigadores guerrerenses. Se realizó un estudio de corte transversal con 67 fumigadores y 46 en el grupo testigo. Se aplicó un instrumento para conocer sus prácticas laborales, plaguicidas utilizados y medidas antropométricas. Las concentraciones séricas de PON1 fueron cuantificadas por enzimoinmunoanálisis de adsorción (ELISA, por su sigla en inglés). Los resultados mostraron que los fumigadores utilizan principalmente carbamatos (38 %) y OF (32 %). Las concentraciones de PON1 fueron de 21.2 ng/mL en los fumigadores vs. 18.7 ng/ml en el grupo testigo. Encontramos que el índice de masa corporal, los antecedentes de diabetes, la antigüedad en la labor de fumigación, el número de plaguicidas utilizados y el consumo de alcohol, vitaminas y suplementos alimenticios son factores de riesgo asociados a los cambios en la concentración de PON1. Es necesario considerar los factores intrínsecos y extrínsecos de los individuos cuando se evalúan los niveles de PON1.

Abstract Nephrotoxicity and hepatotoxicity are frequently seen adverse effects during cisplatin chemotherapy. In this study, we investigated the effects of agomelatine on cisplatin-induced toxicity in the kidney and liver. Animals were administered with a single dose of cisplatin (7 mg/kg, i.p.) and treated with agomelatine (20 and 40 mg/kg, p.o) for seven days. Renal and hepatic functions were evaluated by measuring concentrations of creatinine, BUN, AST and ALT in the serum. Oxidative stress and protein peroxidation were assessed by measuring SOD, CAT, GSH and AOPP levels in both tissues. Serum PON-1 levels were also evaluated. Histopathological analysis was performed to determined structural changes in the kidney and liver. Agomelatine (20 mg/kg) treatment approximately halved cisplatin-related increase in serum creatinine, BUN, AST and ALT levels. Agomelatine (20 mg/kg) significantly prevented the cisplatin-induced excessive decrease in SOD, CAT, GSH in both tissues and serum PON-1 levels. Agomelatine (20 and 40 mg/kg) protected the structural integrity of the kidney against cisplatin-insult. Although agomelatine (40 mg/kg) protected the kidney and showed parallel results with 20 mg/kg biochemically, it failed to show the same liver tissue effects in both analyses. Although agomelatine protected against cisplatin-induced toxicity in the kidney and liver, care should be taken with higher doses for possible hepatotoxicity. chemotherapy study cisplatininduced induced 7 ( mgkg mg kg i.p. ip i p (2 4 p.o po o days creatinine BUN SOD CAT PON1 PON 1 PON- cisplatinrelated related cisplatininsult. cisplatininsult insult. insult cisplatin-insult (4 2 biochemically analyses i.p

Abstract Associations of the activity of the paraoxonase 1 (PON1) enzyme with boar sperm quality still needs to be characterized, since boar ejaculates present distinct portions with differences in sperm concentration and quality. This study evaluated PON1 activity in the serum, in the distinct portions of boar ejaculates and estimated correlations with sperm quality parameters. Ejaculates and blood samples were collected from six boars for three weeks (two per week per boar; n = 36). Serum and post-spermatic portion PON1 activities were positively correlated (P = 0.01) but were both uncorrelated with the PON1 activity in the sperm-rich portion and in the whole ejaculate (P > 0.05). Differences in PON1 activity among boars were only observed in the sperm-rich portion of the ejaculate (P < 0.05). The PON1 activity in the serum and in the post-spermatic portion was generally negatively correlated with parameters of spermatozoa kinetics (P < 0.05). In the sperm-rich portion, PON1 activity was positively correlated with sperm concentration (P < 0.0001), curvilinear distance and velocity (both P < 0.05) and DNA integrity (P < 0.05), but negatively correlated with straightness and linearity (P < 0.05). Thus, boar ejaculates with increased PON1 activity in the sperm-rich portion may present increased concentration and spermatozoa with acceptable curvilinear velocity and distance and DNA integrity, which suggests that PON1 activity may be a biomarker for potential fertility.

ABSTRACT Objectives: Paraoxonase 1 (PON1) is an enzyme that has antioxidant potential, which confers a protective effect against the atherosclerotic process. However, studies associating genetics, dietary patterns and PON1 activity in individuals with cardiovascular disease (CVD) are scarce. Thus, the aim of the current study was to evaluate the influence of dietary factors on serum PON1 in CVD patients. Subjects and methods: Cross-sectional, sub-study of the BALANCE Program Trial. All patients aged 45 years or older and had evidence of established atherosclerotic disease in the preceding 10 years. Body weight, height, waist circumference, blood pressure, lipid profile and fasting glucose were collected. Food intake was assessed with 24-h dietary recall. Data was analyzed using SAS University Edition and a P value ≤ 0.05 was considered statistically significant. Sample was divided into three groups, according to the PON1 T(-107)C genotype (CC, CT and TT) and serum PON1 activity (Low, Medium, High). Results: There were no genotype differences for major factors. However, the systolic blood pressure was lower for CT individuals (p<0.05). Intake of cholesterol, saturated fatty acids (SFA) and monounsaturated fatty acids (MUFAS) was higher in patients with lower PON1 activity. Lipid ingestion tended to be higher in patients with lower PON1 activity (p=0.08). In the multivariate logistic regression model, SFA intake (P=0.03), genotype (P=0.09), gender (P=0.04), age (P=0.07) and carbohydrate intake (P=0.16) contributed the most to the serum PON1 activity. Conclusion: Based on these findings, nutritional guidance for these patients becomes essential, since dietary components interact with serum PON1 activity more than genotype.

ABSTRACT Objective: The aim of this study was to evaluate the serum activity of PON1 in women according to SNPs L55M and T-107C and diet composition. Materials and methods: Blood and serum samples from 26 women were used. DNA extraction, PCR and digestion with restriction enzymes of the PCR fragment were performed for genotyping the PON1 SNPs T-107C and L55M. Serum PON1 activity was measured in a single time point. Patients completed the semi-quantitative food frequency questionnaire and diet composition was estimated. Results: Genotypic distribution for L55M SNP was 56% for the LL genotype, 32% for LM and 12% for MM; for the PON1 C(-107)T SNP it was 28% for the TT genotype, 41% for CT and 31% for CC. Individuals with C and L alleles had higher serum PON1 activity. Combining the two SNPs, we observed that individuals carrying the LL and CC genotypes had twice the activity of carriers of the TT and MM genotypes. Considering food intake, no significant difference was observed between genotypes and intake levels. Conclusion: PON1 T(-107)C and L55M SNPs exert a strong effect on serum PON1 activity in an additive manner and are more important than diet to predict serum PON1 activity.