Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population.

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.

Preliminary survey of the occurrence of mycotoxins in cereals and estimated exposure in a northwestern region of Mexico.

Mycotoxins have several toxicological implications. In the present study, we evaluate the presence of aflatoxin B1 (AFB1), ochratoxin A (OTA), and fumonisin (FB1) in paddy rice, polished rice, and maize from the fields and markets in Nayarit State (Mexico). The results indicated the presence of AFB1 in 21.21% of paddy rice samples and 11.11% of market maize samples. OTA was present in only 3.03% (one sample) of paddy rice samples. FB1 was detected in 87.50% and 88.88% of maize samples from field and market, respectively. The estimated human exposure was calculated for FB1 using the probable daily intake (PDI), which suggested that FB1 could contribute to the development of diseases through the consumption of contaminated maize. Positive samples indicated that some rice and maize samples were not suitable for human consumption. Further efforts are needed to continue monitoring mycotoxins and update national legislation on mycotoxins accordingly.

The effectiveness of educational programmes in promoting sun protection among children under the age of 18: a systematic review and meta-analysis.

Childhood ultraviolet radiation exposure has a strong connection to the development of skin cancer in later life. Therefore, there have been numerous sun protection educational programmes targeted to this age group. However, the association between these have not been well established. This systematic review aims to summarize the evidence on, and assess, the effectiveness of educational programmes in improving sun protection among children under age-18. The protocol was prospectively registered in the PROSPERO database (CRD42020178264). Per PRISMA guidelines, bibliographic databases CENTRAL, OVID (EMBASE, MEDLINE, PsycINFO), LILACS, trial registries, grey literature and other sources were systematically searched for randomized controlled and clinical controlled trials published between database inception to 9 June 2020. Dual independent review of abstracts and full texts was performed. Eligible studies were assessed for methodological quality using the Cochrane risk-of-bias tool. The primary outcome was postintervention scores [standardized mean difference (SMD)] for sun protection (i) knowledge (ii) attitudes and beliefs (iii) behavioural intentions and behaviours. Sidik-Jonkman random effects meta-analysis, sensitivity and subgroup analyses were performed for specific outcomes (sunscreen and sun-safe hat use) which were sufficiently reported. 1350 publications were identified and 24 eligible trials, conducted across 8 different countries, with sufficient aggregate data were included. Small-to-moderate effects of educational programmes were observed across all sun protection outcomes of interest, but negligible effect sizes were demonstrated when specific outcomes were meta-analysed - sunscreen use, SMD 0.18 (95% CI 0.07-0.29; n = 8) and sun-safe hat use, SMD 0.08 (95% CI, 0.00-0.16; n = 6). A promising approach in the future may be to consider targeting children in secondary education with a digitally delivered interactive intervention. Current evidence, however, is insufficient to assess the effects of potential moderators and change in sun protection outcomes is likely not one-size-fits-all. Further research is warranted to direct intervention design and public policy.

PON1 status and homocysteine levels as potential biomarkers for cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death. The mainly risks factors for CVD are diabetes, hypertension and high levels of homocysteine (Hcys), among others. Paraoxonase 1 (PON1) has been proposed as an antiatherogenic target for its ability to hydrolyzing oxi-Low-Density-Lipoproteins (LDL) and Hcys-thiolactone. Thus, the aim of the present study was to evaluate the association of Hcys levels, and the activities and concentration of PON1, as well as vitamin B from the diet with a risk for CVD. METHODS: A case-control study was carry out in patients with cardiovascular diseases (CVD), Arterial hypertension, but not CVD (AH), and in healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, intake of vitamin B, Hcys, serum amyloid A (SAA), PON1 concentration, and PON1 activities (Arylesterase activity (ARE), Lactonase activity (LAC), and CMPA activity (CMPA)) were evaluated. RESULTS: The CVD group had the highest concentration of Hcys and SAA than in the AH and control groups (p < 0.01). ARE, LAC, and CMPA activities and PON1 concentration were lowest in the CVD group. A positive-independent association between Hcys levels and CVD was found (OR = 2.09; 95% CI: 1.69-2.56) and this increase when it was adjusted by age, BMI, ApoA1, vitamin B intake, SAA, and PON1 (OR = 14.41; 95% CI: 1.75-118.71). LAC and CMPA, as well as PON1 concentration, were inversely associated with CVD. CONCLUSION: LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD and their association could be modified by the intake of vitamin B.

PON1 lactonase activity and its association with cardiovascular disease.

BACKGROUND: Paraoxonase 1 (PON1) is important in the development of atherosclerosis, and it has become the subject of intensive research. Our aim was to evaluate the association of serum PON1 activity and polymorphisms with cardiovascular disease (CVD) using four different substrates. MATERIALS AND METHODS: Activity of PON1-related to arylesterase (AREase and 4-CMPAse), paraoxonase (PONase), and lactonase (LACase), and polymorphisms (A-162G, T-108C, L55M, and Q192R) were evaluated in subjects with CVD, cardiovascular risk factor (CFR), and controls. An ordered logistic-regression analysis of PON1 phenotypes was performed in the CVD group with respect to the control group. RESULTS AND CONCLUSIONS: Logistic-regression analysis showed that CC-108 genotype was associated with CRF and CVD. The CVD group had the lowest activities of PON1. The LACase might be a better biomarker for CVD (OR, 0.52; 95% CI, 0.44-0.61) followed by CMPAse (OR, 0.82; 95% CI, 0.77-0.86), AREase (OR, 0.98; 95% CI, 0.97-0.99) and PONase (OR, 0.99, 95% CI, 0.99-0.99). Logistic regression of PON1 phenotypes by haplotypes showed that LACase activity was not influenced by the polymorphisms and that it could be a new potential biomarker in the development of CVD. Larger scale longitudinal studies are required.

Systematic review of the influence of socioeconomic deprivation on mortality after colorectal surgery.

BACKGROUND: Socioeconomic deprivation is a potentially important factor influencing surgical outcomes. This systematic review aimed to summarize the evidence for any association between socioeconomic group and mortality after colorectal surgery, and to report the definitions of deprivation used and the approaches taken to adjust for co-morbidity in this patient population. METHODS: MEDLINE, Embase, the Cochrane Library and Web of Science were searched for studies up to November 2016 on adult patients undergoing major colorectal surgery, which reported on mortality according to socioeconomic group. Risk of bias and study quality were assessed by extracting data relating to study size, and variations in inclusion and exclusion criteria. Quality was assessed using a modification of a previously described assessment tool. RESULTS: The literature search identified 59 studies published between 1993 and 2016, reporting on 2 698 403 patients from eight countries. Overall findings showed evidence for higher mortality in more deprived socioeconomic groups, both in the perioperative period and in the longer term. Studies differed in how they defined socioeconomic groups, but the most common approach was to use one of a selection of multifactorial indices based on small geographical areas. There was no consistent approach to adjusting for co-morbidity but, where this was considered, the Charlson Co-morbidity Index was most frequently used. CONCLUSION: This systematic review suggests that socioeconomic deprivation influences mortality after colorectal surgery.

Transcriptional regulation of human Paraoxonase 1 by nuclear receptors.

Paraoxonase 1 (PON1) is a calcium-dependent lactonase synthesized primarily in the liver and secreted into the plasma, where it is associates with high density lipoproteins (HDL). PON1 acts as antioxidant preventing low-density lipoprotein (LDL) oxidation, a process considered critical in the initiation and progression of atherosclerosis. Additionally, PON1 hydrolyzes and detoxifies some toxic metabolites of organophosphorus compounds (OPs). Thus, PON1 activity and expression levels are important for determining susceptibility to OPs intoxication and risk of developing diseases related to inflammation and oxidative stress. Increasing evidence has demonstrated the modulation of PON1 expression by many factors is due to interaction with nuclear receptors (NRs). Here, we briefly review the studies in this area and discuss the role of nuclear receptors in the regulation of PON1 expression, as well as how understanding these mechanisms may allow us to manipulate PON1 levels to improve drug efficacy and treat disease.

Effects of diazinon on the lymphocytic cholinergic system of Nile tilapia fish (Oreochromis niloticus).

Fish rearing under intensive farming conditions can be easily disturbed by pesticides, substances that have immunotoxic properties and may predispose to infections. Organophosphorus pesticides (OPs) are widely used in agricultural activities; however, the mechanism of immunotoxicity of these substances is unclear. The aim of this study was to evaluate the effect of diazinon pesticides (OPs) on the cholinergic system of immune cells as a possible target of OP immunotoxicity. We evaluated ACh levels and cholinergic (nicotinic and muscarinic) receptor concentration. Additionally, AChE activity was evaluated in mononuclear cells of Nile tilapia (Oreochromis niloticus), a freshwater fish mostly cultivated in tropical regions around the world. The obtained results indicate that acute exposure to diazinon induces an increase in ACh concentration and a decrease in nAChR and mAChR concentrations and AChE activity in fish immune cells, This suggests that the non-neuronal lymphocytic cholinergic system may be the main target in the mechanism of OP immunotoxicity. This study contributes to the understanding of the mechanisms of immunotoxicity of pollutants and may help to take actions for animal health improvement.

Assessment of pollution of the Boca de Camichin Estuary in Nayarit (Mexico) and its influence on oxidative stress in Crassostrea corteziensis oysters.

Boca de Camichin Estuary is one of the main producers of Crassostrea corteziensis oysters in Mexico, but the presence of pollutants can affect oyster production. Molluscs produce reactive oxygen species (ROS) in response to changes in the environment and pollution. These ROS induce oxidative damage in biomolecules. The main objective of this study was to evaluate pollution in the estuary and the subsequent oxidative stress in C. corteziensis oysters during the 2010 production cycle. For this aim, we performed monthly samplings in the oyster farms from January to May. We took water samples to quantify polycyclic aromatic hydrocarbon (PAH) and metal content; also, we evaluated oxidative damage (lipoperoxidation, lipidic hydroperoxides, protein oxidation) and enzyme activity (CAT, SOD, GPx, GST and AChE) in oyster gills. The results show the presence of Cu, Fe, Mn, naphthalene, benz[a]anthracene, pyrene, benz[a]pyrene and benzo[k]fluoranthene. On the other hand, AChE activity was not inhibited, which suggests that organophosphorus pollutants or carbamates were absent. Regarding oxidative stress, oysters from the estuary had oxidative damage in lipids, not proteins, and altered antioxidant enzyme activity, when compared to control organisms. Interestingly, we did not observe any correlation between the pollutants and the oxidative stress parameters evaluated in this study. Thus, we cannot rule out that a synergistic effect between the environmental variables and the pollutants is causing the oxidative stress in these oysters.

Transcriptional regulation of human paraoxonase 1 by PXR and GR in human hepatoma cells.

Human paraoxonase 1 (PON1) is A-esterase synthesized in the liver and secreted into the plasma, where it associates with HDL. PON1 acts as an antioxidant preventing lipid oxidation and detoxifies a wide range of substrates, including organophosphate compounds. The variability of PON1 (enzyme activity/serum levels) has been attributed to internal and external factors. However, the molecular mechanisms involved in the transcriptional regulation of PON1 have not been well-studied. The aim of this study was to evaluate and characterize the transcriptional activation of PON1 by nuclear receptors (NR) in human hepatoma cells. In silico analysis was performed on the promoter region of PON1 to determine the response elements of NR. Real-time PCR was used to evaluate the effect of specific NR ligands on the mRNA levels of genes regulated by NR and PON1. The results indicated that NR response elements had 95% homology to pregnenolone (PXR), glucocorticoids (GR), retinoic acid (RXR) and peroxisomes proliferator-activated receptor alpha (PPARα). Treatments with Dexamethasone (GR ligand), Rifampicin (PXR ligand) and TCDD (AhR ligand) increased the mRNA levels of PON1 at 24 and 48 h. We showed that the activation of GR by Dexamethasone results in PON1 gene induction accompanied by an increase in activity levels. In conclusion, these results demonstrate that GR regulates PON1 gene transcription through directly binding to NR response elements at -95 to -628 bp of the PON1 promoter. This study suggests new molecular mechanisms for the transcriptional regulation of PON1 through a process involving the activation of PXR.

Cytostatic and genotoxic effect of temephos in human lymphocytes and HepG2 cells.

Temephos is an organophosphorus pesticide that is used in control campaigns against Aedes aegypti mosquitoes, which transmit dengue. In spite of the widespread use of temephos, few studies have examined its genotoxic potential. The aim of this study was to evaluate the cytotoxic, cytostatic and genotoxic effects of temephos in human lymphocytes and hepatoma cells (HepG2). The cytotoxicity was evaluated with simultaneous staining (FDA/EtBr). The cytostatic and genotoxic effects were evaluated using comet assays and the micronucleus technique. We found that temephos was not cytotoxic in either lymphocytes or HepG2 cells. Regarding the cytostatic effect in human lymphocytes, temephos (10 µM) caused a significant decrease in the percentage of binucleated cells and in the nuclear division index as well as an increase in the apoptotic cell frequency, which was not the case for HepG2 cells. The comet assay showed that temephos increased the DNA damage levels in human lymphocytes, but it did not increase the MN frequency. In contrast, in HepG2 cells, temephos increased the tail length, tail moment and MN frequency in HepG2 cells compared to control cells. In conclusion, temephos causes stable DNA damage in HepG2 cells but not in human lymphocytes. These findings suggest the importance of temephos biotransformation in its genotoxic effect.

Evaluation of pollution in Camichin estuary (Mexico): pro-oxidant and antioxidant response in oyster (Crassostrea corteziensis).

The physiological system of molluscs, particularly pro-oxidant and antioxidant mechanisms, could be altered by pollutants and induce disturbance on health status and productive parameters of aquatic organisms, such as oyster. Therefore, the aim of this study was to evaluate the chemical contamination in water (total metals and polycyclic aromatic hydrocarbons) and oxidative stress parameters in oysters (Crassostrea corteziensis) in Camichin estuary, located in Mexican Tropical Pacific. The results obtained showed the presence of arsenic, lead and zinc, as well as naphthalene, pyrene and benzo[a]pyrene in concentrations relatively higher than criteria established by local and international guidelines. Regarding the biomarkers of oxidative stress response (H2O2 and O2 concentration, catalase activity, lipid peroxidation, and hydroperoxide concentration), differences between oyster from estuary and control group were significant. These results indicate that these pollutants could be related with oxidative stress detected in oyster.

AKRs expression in peripheral blood lymphocytes from smokers: the role of body mass index.

Aldo-keto reductases (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis. Exposure to PAHs, their metabolites, and ROS further increase AKRs isoform expression that may amplify oxidative damage. Human AKR enzymes are highly polymorphic, and allelic variants may contribute to different AKRs expression in individuals. Despite the importance of AKRs in PAHs metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes (PBLs). The aim of this study was to determine the effect of tobacco smoke exposure, and AKR1A1*2 and AKR1C3*2 polymorphisms, on AKR1A1 and AKR1C1-AKR1C3 messenger RNA (mRNA) levels in PBLs from smokers. In the smoker group, there is a statistically significant positive association between AKR1A1, AKR1C1, and AKR1C3 mRNA induction and urine cotinine levels in individuals with a body mass index (BMI) less than 25. However, AKR1A1*2 and AKR1C3*2 alleles did not influence AKR1A1 and AKR1C1-AKR1C3 mRNA levels. These results suggest that AKRs induction by PAHs in smokers' PBLs is associated with BMI; therefore, the role of adipose tissue accumulation in PAHs' effects needs further investigation.

Organophosphate pesticides increase the expression of alpha glutathione S-transferase in HepG2 cells.

Chlorpyrifos and methyl parathion are among the most widely used insecticides in the world. Human populations are constantly exposed to low doses of both due to their extensive use and presence in food and drinking water. Glutathione S-transferase (GST) catalyzes the conjugation of glutathione on electrophilic substrates and is an important line of defense in the protection of cellular components from reactive species. GST alpha1 (GSTA1) is the predominant isoform of GST expressed in the human liver; thus, determining the effect of insecticides on GSTA1 transcription is very important. In the present study, we analyzed the effects of methyl parathion and chlorpyrifos on GSTA1 gene expression in HepG2 cells using real time PCR, and activity and immunoreactive protein assays. The results demonstrated that exposure to methyl parathion and chlorpyrifos increased the level of GSTA1 mRNA, GSTA1 immunoreactive protein and GST activity relative to a control. These results demonstrated that these insecticides can increase the expression of GSTA1. In conclusion, HepG2 cell cultures treated with methyl parathion and chlorpyrifos could be a useful model for studying the function of GSTA1 and its role in the metabolism of xenobiotics in the liver.

Phytoremediatory effect and growth of two species of Ocimum in endosulfan polluted soil.

Endosulfan is a hazardous organochlorine pesticide banned or restricted in several countries. However, it has been found in the environment and in animal samples. To study a potential way to bioremediate soils contaminated with this pesticide, two plant species of the genus Ocimum were studied: Ocimum basilicum L. and Ocimum minimum L., since they are economically feasible and well adapted to the climatic conditions of the Nayarit zone (Mexican pacific coast). Young plants were transplanted into soil experimentally polluted with endosulfan. Growth of both species was not affected by endosulfan, the plants grew, flourished, and produced seeds; 30 days later, endosulfan concentration was lower in the soil with O. basilicum than in the soil without plants. On day 90, no differences in endosulfan concentrations were found between soil with or without O. minimum. At day 1, plants in the polluted soil showed lipoperoxidation, as measured by thiobarbituric acid-reactive species (TBARS). Interestingly, a higher TBARS value was observed at day 3 in transplanted plants as compared to non-transplanted plants. In conclusion, both species can endure endosulfan pollution (as high as 1 g kg(-1)) in soils. O. basilicum seems to be an adequate candidate for bioremediation of soils polluted with endosulfan.

Análisis del deseo sexual en una muestra de drogodependientes en periodo de abstinencia / Analysis of sexual desire in a sample of drug addicts in abstinence period

Objetivos. El propósito de esta investigación fue analizar qué variables influían en el deseo sexual en drogodependientes en periodo de abstinencia. Los objetivos planteados son: a) comparar los niveles de deseo sexual entre sujetos drogodependientes en periodo de abstinencia y sujetos sin historia de consumo de drogas; b) determinar, en sujetos drogodependientes en periodo de abstinencia la relación entre la edad y tener pareja con el deseo sexual; c) examinar, en sujetos drogodependientes en periodo de abstinencia, la relación entre estados emocionales y deseo sexual; y d) determinar, en sujetos drogodependientes en periodo de abstinencia, qué variables tienen mayor capacidad de predicción del deseo sexual. Métodos. La muestra estuvo formada por 100 hombres cuya edad osciló entre 19 y 72 años, pertenecientes a distintos programas de tratamientos en drogadicción. Además, se utilizó una muestra de 46 varones sin historia de consumo de drogas con edades entre 18 y 81 años. Resultados. Los análisis no ofrecieron diferencias entre los diferentes grupos (alcohol, cocaína, heroína más cocaína y sujetos sin historia de consumo de drogas), ni en deseo sexual diádico (F3,125 = 0,71, p = 0,543), ni en deseo sexual solitario (F3,125 = 0,73, p = 0,535). Las variables ansiedad estado y edad mostraron capacidad predictiva (F2,70 = 6,56; p < 0,01), presentando ambas una relación negativa con el deseo sexual diádico, en sujetos drogodependientes en periodo de abstinencia. Conclusiones. No parecen existir diferencias entre población sin historia de consumo de drogas y drogodependientes en periodo de abstinencia en deseo sexual. En estos últimos, existe relación entre una alta ansiedad estado y un nivel de deseo sexual diádico bajo, así como una relación negativa de la edad conjuntamente con la ansiedad estado, con respecto al deseo sexual diádico (AU)

Objective. The purpose of this work was to analyse which variables influence sexual desire in a drug abusers sample during periods of abstinence. The objectives were: a) to compare levels of sexual desire among subjects with a history of drug abuse and subjects without a history of drug abuse; b) to determine the relation between age and having sexual partner or not in subjects with a history of drug abuse; c) to examine the relation among anxiety and depression and sexual desire in subjects with a history of drug abuse; d) to determine which variables predict sexual desire in subjects with a history of drug abuse. Methods. Research was with a sample of 100 men (aged 19 to 72) who belong to drug addiction treatment programs. Furthermore, there was another sample of 46 men (aged 18 to 81) without a history of drug abuse. Results. The analysis did not show differences among the groups (alcohol, cocaine, heroin plus cocaine and subjects without a history of drug abuse) in dyadic sexual desire (F3,125 =0.71, p =0.543) and solitary sexual desire (F3,125 =0.73, p =0.535). However, the variables of anxiety state and age showed predictive capacity for dyadic sexual desire in subjects with a history of drug abuse. Conclusions. In sexual desire there is no difference between subjects without a history of drug abuse and drug addicts during periods of abstinence. In subjects with a history of drug abuse there is a negative relationship between anxiety state and down levels of dyadic sexual desire, and a negative relation between age in conjunction with anxiety state (AU)

Acetylcholinesterase and metallothionein in oysters (Crassostrea corteziensis) from a subtropical Mexican Pacific estuary.

Substantial efforts have been devoted to developing and applying biomarkers for ecological risk assessment. Bivalve mollusks, such as mussels and oysters, are commonly used in environmental monitoring programs because of their wide geographical distribution, great sensitivity to environmental pollutants, and ability to accumulate anthropogenically derived chemicals at a high rate. Acetylcholinesterase (AChE) activity and metallothionein (MT's) content are representative specific biomarkers that indicate the presence of anticholinesterasic compounds (like organophosphorus and carbamate pesticides) and metals, respectively. The aim of this study was to evaluate AChE activity and MT's content in Crassostrea corteziensis from Boca de Camichín estuary. The results obtained here showed that AChE activity was 65% lower in oysters from Boca de Camichín than in control organisms. In contrast, MT's content in collected organisms was not statistically different from that in control organisms. AChE activity and MT's content in oysters could be used as early biomarkers of effects and exposure to pesticides and heavy metals, respectively, in aquatic environments.

Immunologic parameters evaluations in Nile tilapia (Oreochromis niloticus) exposed to sublethal concentrations of diazinon.

Fish resistance to microorganisms depends basically on the immune response. Although there are several studies on the diazinon mammalian immunotoxicity, in the case of fish there are only few. The aim of present study was to evaluate the effect of diazinon on immunological parameters (relative spleen weight, splenocytes count, lysozyme activity, respiratory burst and IgM concentration) in Nile tilapia. Diazinon at sublethal concentrations (0.39 and 0.78 mg/L) did not alter RSW, splenocytes count or lysozyme activity. However, at the highest concentration tested (1.96 mg/L) diazinon significantly increased respiratory burst and IgM concentration. In summary, diazinon (and perhaps other pesticides) could alter immunological response and induce oxidative stress.

Genetic damage caused by methyl-parathion in mouse spermatozoa is related to oxidative stress.

Organophosphorous (OP) pesticides are considered genotoxic mainly to somatic cells, but results are not conclusive. Few studies have reported OP alterations on sperm chromatin and DNA, and oxidative stress has been related to their toxicity. Sperm cells are very sensitive to oxidative damage which has been associated with reproductive dysfunctions. We evaluated the effects of methyl-parathion (Me-Pa; a widely used OP) on sperm DNA, exploring the sensitive stage(s) of spermatogenesis and the relationship with oxidative stress. Male mice (10-12-weeks old) were administered Me-Pa (3-20 mg/kg bw/i.p.) and euthanized at 7- or 28-days post-treatment. Mature spermatozoa were obtained and evaluated for chromatin structure through SCSA (Sperm Chromatin Structure Assay; DNA Fragmentation Index parameters: Mean DFI and DFI%) and chromomycin-A(3) (CMA(3))-staining, for DNA damage through in situ-nick translation (NT-positive) and for oxidative stress through lipid peroxidation (LPO; malondialdehyde production). At 7-days post-treatment (mature spermatozoa when Me-Pa exposure), dose-dependent alterations in chromatin structure (Mean DFI and CMA(3)-staining) were observed, as well as increased DNA damage, from 2-5-fold in DFI% and NT-positive cells. Chromatin alterations and DNA damage were also observed at 28-days post-treatment (cells at meiosis at the time of exposure); suggesting that the damage induced in spermatocytes was not repaired. Positive correlations were observed between LPO and sperm DNA-related parameters. These data suggest that oxidative stress is related to Me-Pa alterations on sperm DNA integrity and cells at meiosis (28-days post-treatment) and epididymal maturation (7-days post-treatment) are Me-Pa targets. These findings suggest a potential risk of Me-Pa to the offspring after transmission.

Genetic polymorphisms and activity of PON1 in a Mexican population.

Human paraoxonase (PON1) plays a role in detoxification of organophosphorus (OP) compounds by hydrolyzing the bioactive oxons, and in reducing oxidative low-density lipoproteins, which may protect against atherosclerosis. Some PON1 polymorphisms have been found to be responsible for variations in catalytic activity and expression and have been associated with susceptibility to OP poisoning and vascular diseases. Both situations are of public health relevance in Mexico. Therefore, the aim of this study was to evaluate PON1 phenotype and the frequencies of polymorphisms PON1 -162, -108, 55, and 192 in a Mexican population. The studied population consisted of unrelated individuals (n = 214) of either gender, 18-52 years old. Serum PON1 activity was assayed using phenylacetate and paraoxon as substrates. PON1 variants, -162, 55, and 192, were determined by real-time PCR using the TaqMan System, and PON1 -108 genotype by PCR-RFLP. We found a wide interindividual variability of PON1 activity with a unimodal distribution; the range of enzymatic activity toward phenylacetate was 84.72 to 422.0 U/mL, and 88.37 to 1645.6 U/L toward paraoxon. All four PON1 polymorphisms showed strong linkage disequilibrium (D% >90). PON1 polymorphisms -108, 55, and 192 were independently associated with arylesterase activity; whereas the activity toward paraoxon was related only with PON1 192 polymorphism, suggesting that this polymorphism is determinant to infer PON1 activity. A better understanding of the phenotype and genotypes of PON1 in Mexican populations will facilitate further epidemiological studies involving PON1 variability in OP poisoning and in the development of atherosclerosis.