Trends on deaths from acute pesticide poisoning in Mexico, 2000-2021.

OBJETIVE: To provide a comprehensive analysis of mortality trends from acute pesticide poisoning in Mexico from 2000 through 2021. METHODS: The governmental records of deaths from acute pesticide poisoning were used. The age-standardized years of life lost and aged-standardized mortality rates were estimated. Significant changes in trends of annual percentage change were identified using Joinpoint regression. RESULTS: Between 2000 and 2021, mortality was primarily observed in individuals aged 15 to 19 years. Males were the most affected. Self-inflicted pesticide poisoning was the primary registered reason for death. The age-standardized mortality rate from acute pesticide poisoning was reduced from 2012 to 2021 (APC: -4.4; p=0.003). CONCLUSION: This report is the first study about the mortality rate from acute pesticide poisoning in Mexico. The results provided evidence to consider in developing laws to prevent acute pesticide poisoning.

Trends on deaths from acute pesticide poisoning in Mexico, 2000-2021 / Tendências das mortes por intoxicação aguda por pesticidas no México, 2000-2021

ABSTRACT Objetive: To provide a comprehensive analysis of mortality trends from acute pesticide poisoning in Mexico from 2000 through 2021. Methods: The governmental records of deaths from acute pesticide poisoning were used. The age-standardized years of life lost and aged-standardized mortality rates were estimated. Significant changes in trends of annual percentage change were identified using Joinpoint regression. Results: Between 2000 and 2021, mortality was primarily observed in individuals aged 15 to 19 years. Males were the most affected. Self-inflicted pesticide poisoning was the primary registered reason for death. The age-standardized mortality rate from acute pesticide poisoning was reduced from 2012 to 2021 (APC: -4.4; p=0.003). Conclusion: This report is the first study about the mortality rate from acute pesticide poisoning in Mexico. The results provided evidence to consider in developing laws to prevent acute pesticide poisoning.

RESUMO Objetivo: Fornecer uma análise abrangente das tendências de mortalidade por envenenamento agudo por pesticidas no México de 2000 a 2021. Métodos: Foram usados os registros governamentais de mortes por envenenamento agudo por pesticidas. Foram estimados os anos de vida perdidos estandardizados por idade e as taxas de mortalidade estandardizados por idade. Modificações significativas nas tendências de variação percentual anual foram identificadas usando a regressão Joinpoint. Resultados: Entre 2000 e 2021, a mortalidade foi observada principalmente em indivíduos na faixa etária de 15 a 19 anos. Os homens foram os mais afetados. O envenenamento por pesticida autoinfligido foi o principal motivo de morte registrado. A taxa de mortalidade estandardizada por idade por intoxicação aguda por pesticidas foi reduzida de 2012 a 2021 (Annual Percent Change — APC: -4,4; p=0,003). Conclusão: Este relatório é o primeiro estudo sobre a taxa de mortalidade por intoxicação aguda por pesticidas no México. Os resultados forneceram evidências a serem consideradas no desenvolvimento de leis para prevenir o envenenamento agudo por pesticidas.

Evaluation of the cytotoxicity and genotoxicity of glufosinate-ammonium at technical and commercial grades in HepG2 cells.

Exposure to genotoxic agents is associated with the development of cancer and related diseases. For this reason, assessing the genotoxicity of chemical compounds is necessary. In this line, information about the genotoxic effect of glufosinate-ammonium (GLA) has been reported only for the technical grade. However, humans are frequently exposed to commercial formulations of pesticides. Commercial formulations are characterized by using inner agents that increase toxicity compared to pesticides in technical grade. This study aimed to determine the cytotoxic and genotoxic effects of GLA on HepG2 cells. MTT and comet assays were performed to evaluate cell viability and DNA damage, respectively. HepG2 cells were exposed for 24 h to different concentrations of GLA (at 0.01 µg/mL; 0.04 µg/mL; 0.1 µg/mL; 0.24 µg/mL; 0.52 µg/mL; 1.25 µg/mL; 2.62 µg/mL and 13.12 µg/mL) in commercial- (Finale Ultra®) or technical-grade (GLAT). The results indicated that only Finale Ultra® induced a reduction in cell viability at 13.12 µg/mL. Furthermore, exposure to Finale Ultra® or GLAT was associated with increased DNA damage at concentrations from 0.52-13.12- µg/mL. This study shows the genotoxic effect of GLA on HepG2 cells.

Effects of exposure to environmental pollutants on mitochondrial DNA copy number: a meta-analysis.

Exposure to environmental pollutants has been associated with alteration on relative levels of mitochondrial DNA copy number (mtDNAcn). However, the results obtained from epidemiological studies are inconsistent. This meta-analysis aimed to evaluate whether environmental pollutant exposure can modify the relative levels of mtDNAcn in humans. We performed a literature search using PubMed, Scopus, and Web of Science databases. We selected and reviewed original articles performed in humans that analyzed the relationship between environmental pollutant exposure and the relative levels of mtDNAcn; the selection of the included studies was based on inclusion and exclusion criteria. Only twenty-two studies fulfilled our inclusion criteria. A total of 6011 study participants were included in this systematic review and meta-analysis. We grouped the included studies into four main categories according to the type of environmental pollutant: (1) heavy metals, (2) polycyclic aromatic hydrocarbons (PAHs), (3) particulate matter (PM), and (4) cigarette smoking. Inconclusive results were observed in all categories; the pooled analysis shows a marginal increase of relative levels of mtDNAcn in response to environmental pollutant exposure. The trial sequential analysis and rate confidence in body evidence showed the need to perform new studies. Therefore, a large-scale cohort and mechanistic studies in this area are required to probe the possible use of relative levels of mtDNAcn as biomarkers linked to environmental pollution exposure.

Influence of Diet and Levels of Zonulin, Lipopolysaccharide and C-Reactive Protein on Cardiometabolic Risk Factors in Young Subjects.

A western diet and increased intestinal permeability may contribute to systemic inflammation and the development of cardio-metabolic alterations. The aim of this study was to assess the relationship between diet, biomarkers of intestinal permeability, and chronic low-grade inflammation on the cardiometabolic profile. A cross-sectional study was carried out in 238 young subjects aged 18-29 years, divided into two groups: with <3 cardiometabolic risk factors (CRF) and ≥3 risk factors. Anthropometric parameters, biochemical profile, and serum levels of zonulin, lipopolysaccharide (LPS), and high-sensitivity C-reactive protein (hs-CRP) were measured, and the macronutrient intake was evaluated. Interaction models showed elevated glucose levels in the presence of high biomarker levels: zonulin ≥51.6 ng/mL plus LPS ≥ 1.35 EU/mL (ß = 1.1, p = 0.006), and LPS ≥1.35 EU/mL plus hs-CRP ≥ 4.3 mg/L (ß = 1.2, p = 0.007). In addition, triglyceride levels increased in the presence of LPS ≥ 1.35 EU/mL and hs-CRP ≥ 4.3 mg/L (ß = 3.9, p = 0.01). Despite having increased biomarker levels, a higher consumption of water (≥2100 mL), polyunsaturated fatty acids (≥6.0 g), or fiber (≥30 g) decreased triglyceride (ß = -9.6, p = 0.03), total cholesterol (ß = -5.1, p = 0.01), and LDL-C levels (ß = -7.7, p = 0.01). These findings suggest that the increased consumption of water, PUFA and fiber may improve lipid profile in subjects with intestinal permeability dysfunction or low-grade systemic inflammation.

Organophosphorus pesticide exposure biomarkers in a Mexican population.

The organophosphate (OP) pesticides are neurotoxic compounds widely used around the world. Evaluation of OP exposure in human studies is important for enabling adequate data analyses and drawing accurate conclusions. The aim of this study was to analyze OP exposure biomarkers and their relationships in a Mexican population with different exposure levels. Dialkylphosphates (DAP) were determined through gas chromatography-mass spectrometry (GC-MSD); acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), arylesterase (AREase), basal paraoxonase 1 (PONase), and ß-glucuronidase activities were detected using spectrophotometric methods. The albumin content was determined in a certified clinical laboratory. The DMTP metabolite was found in the highest concentration, and a negative and significant correlation between DAP and cholinesterase activity was observed. Our results suggested that BuChE is a considerably more sensitive biomarker than AChE. In addition, ß-glucuronidase was positively correlated with albumin, BuChE, and PONase. In conclusion, our data strongly support the use of two or more biomarkers of exposure in human monitoring and the application of a strong and validated questionnaire.

Significant decrease of a master regulator of genes (REST/NRSF) in high-grade squamous intraepithelial lesion and cervical cancer.

BACKGROUND: The repressor element 1-silencing transcription factor (REST) is a regulator of gene expression, and the Ras association domain family member 1 A (RASSF1A) is an important tumor suppressor gene involved in cancer development. Although extensive characterization of the roles of REST and RASSF1A in cancer development have been reported in cellular models, the link between them and their possible role in the development of squamous intraepithelial lesions (SIL) and squamous cell carcinoma (SCC) of the cervix have not been explored. The aim of this study was to evaluate the expression of REST and RASSF1A in cervical cytological and histological samples from patients diagnosed with SIL or SCC and in CC-derived cell lines. METHODS: We analyzed the expression of REST and RASSF1A by immunocyto/histochemistry in cervical samples from patients (n = 271) and in cancer cell lines. Data analyses were performed using the Kruskal-Wallis test and generalized linear models. RESULTS: We identified binding sites for REST in RASSF1A and observed a significant reduction in REST and RASSF1A nuclear expression in samples from patients with high-grade SIL (HSIL) and SCC. For REST, we observed an average decrease of 334 and 423 r.u.d. for HSIL (n = 21) and SCC (n = 18) compared with non-LSIL (n = 72), whereas for RASSF1A, this decrease was 126 and 217 r.u.d., respectively (p < 0.001). CONCLUSION: Our results provide evidence of the altered expression of REST and RASSF1A in SIL and SCC, with a significant decrease in HSIL, SCC, and SCC-derived cell lines; findings that can contribute to the diagnosis, prognosis, and post-treatment follow-up of patients diagnosed with SIL or SCC.

PON-1 haplotype (-108C>T, L55M, and Q192R) modulates the serum levels and activity PONase promoting an atherogenic lipid profile in rheumatoid arthritis patients.

INTRODUCTION/OBJECTIVE: Paraoxonase 1 (PON1) promotes antioxidant and antiatherogenic activity related to the hydrolysis of oxidized lipids of low-density lipoproteins. In rheumatoid arthritis (RA) patients, it has been reported that low PON1 activity is related to an impaired lipid profile, increasing cardiovascular risk (CVR). The goal of this study was to analyze the effect of common PON1 polymorphisms and haplotypes on enzymatic activity, PON1 serum levels (PON1s), and lipid parameters related to atherogenic profile in RA patients. METHODS: A cross-sectional study was carried out on 250 Mexican patients with RA. The lipid profile was determined by colorimetric tests. The PON1 activity (CMPAase) was measured by spectrophotometry. The levels of PON1s were determined by ELISA, and the polymorphisms in the PON-1 gene (-108C>T, L55M, and Q192R) were genotyped by the PCR-RFLP method. The haplotypes were estimated and statistical analysis was performed. RESULTS: The median of the CMPAase activity and PON1 levels was 13.91 U/mL and 24.75 ng/mL, respectively. The CMPAase activity was significantly lower in carriers of -108TT and 192QQ genotypes (ß = - 4.09, P = 0.001 and ß = - 3.73, P = 0.002, respectively); moreover, the PON1 levels were lower in 192Q allele carriers (P < 0.01). The TLQ haplotype was associated with CMPAase activity < 13.91 U/mL (OR = 2.29, P < 0.001), as well as with levels of PON1s < 24.75 ng/mL (OR = 1.65, P = 0.017). In this study, the CMPAase activity (< 13.91 U/mL) showed a positive association with lower levels of high-density lipoprotein cholesterol (HDL-c; < 40/50 mg/dL), and with a triglycerides/HDL-c ratio > 3%, and a total cholesterol/HDL-c ratio > 4.5/5%, all representatives of an atherogenic risk lipid profile. CONCLUSIONS: PON1 polymorphisms modulate the CMPAase activity and PON1 levels in Mexican patients with RA. The CMPAase activity < 13.91 U/mL is associated with an atherogenic lipid profile, independently of inflammation markers and treatment with anti-rheumatic drugs. Key Points •The haplotype TLQ is a marker for low PONase activity in rheumatoid arthritis. •The haplotype TLQ is a marker for low PON1 serum levels in rheumatoid arthritis. •The enzymatic PON1 activity represents the best marker for an atherogenic lipid profile in rheumatoid arthritis, in comparison with PON1 levels. •The haplotype TLQ is a marker of low PON1 activity, levels of PON1s, and atherogenic lipid profile, independent of treatment therapy in rheumatoid arthritis.

Leptin induces cell migration and invasion in a FAK-Src-dependent manner in breast cancer cells.

Breast cancer is the most common invasive neoplasia, and the second leading cause of the cancer deaths in women worldwide. Mammary tumorigenesis is severely linked to obesity, one potential connection is leptin. Leptin is a hormone secreted by adipocytes, which contributes to the progression of breast cancer. Cell migration, metalloproteases secretion, and invasion are cellular processes associated with various stages of metastasis. These processes are regulated by the kinases FAK and Src. In this study, we utilized the breast cancer cell lines MCF7 and MDA-MB-231 to determine the effect of leptin on FAK and Src kinases activation, cell migration, metalloprotease secretion, and invasion. We found that leptin activates FAK and Src and induces the localization of FAK to the focal adhesions. Interestingly, leptin promotes the activation of FAK through a Src- and STAT3-dependent canonical pathway. Specific inhibitors of FAK, Src and STAT3 showed that the effect exerted by leptin in cell migration in breast cancer cells is dependent on these proteins. Moreover, we established that leptin promotes the secretion of the extracellular matrix remodelers, MMP-2 and MMP-9 and invasion in a FAK and Src-dependent manner. Our findings strongly suggest that leptin promotes the development of a more aggressive invasive phenotype in mammary cancer cells.

Biotransformation of benzo[a]pyrene by the thermophilic bacterium Bacillus licheniformis M2-7.

Benzo[a]pyrene (BaP) is recognized as a potentially carcinogenic and mutagenic hydrocarbon, and thus, its removal from the environment is a priority. The use of thermophilic bacteria capable of biodegrading or biotransforming this compound to less toxic forms has been explored in recent decades, since it provides advantages compared to mesophilic organisms. This study assessed the biotransformation of BaP by the thermophilic bacterium Bacillus licheniformis M2-7. Our analysis of the biotransformation process mediated by strain M2-7 on BaP shows that it begins during the first 3 h of culture. The gas chromatogram of the compound produced shows a peak with a retention time of 17.38 min, and the mass spectra shows an approximate molecular ion of m/z 167, which coincides with the molecular weight of the chemical formula C6H4(COOH)2, confirming a chemical structure corresponding to phthalic acid. Catechol 2,3-dioxygenase (C23O) enzyme activity was detected in minimal saline medium supplemented with BaP (0.33 U mg-1 of protein). This finding suggests that B. licheniformis M2-7 uses the meta pathway for biodegrading BaP using the enzyme C23O, thereby generating phthalic acid as an intermediate.

Effects of exposure to malathion on blood glucose concentration: a meta-analysis.

Exposure to malathion (an organophosphate pesticide widely used around the world) has been associated with alterations in blood glucose concentration in animal models. However, the results are inconsistent. The aim of this meta-analysis was to evaluate whether malathion exposure can disturb the concentrations of blood glucose in exposed rats. We performed a literature search of online databases including PubMed, EBSCO, and Google Scholar and reviewed original articles that analyzed the relation between malathion exposure and glucose levels in animal models. The selection of articles was based on inclusion and exclusion criteria. The database search identified thirty-five possible articles, but only eight fulfilled our inclusion criteria, and these studies were included in the meta-analysis. The effect of malathion on blood glucose concentration showed a non-monotonic dose-response curve. In addition, pooled analysis showed that blood glucose concentrations were 3.3-fold higher in exposed rats than in the control group (95% CI, 2-5; Z = 3.9; p < 0.0001) in a random-effect model. This result suggested that alteration of glucose homeostasis is a possible mechanism of toxicity associated with exposure to malathion.

Genotypes of Common Polymorphisms in the PON1 Gene Associated with Paraoxonase Activity as Cardiovascular Risk Factor.

BACKGROUND: Paraoxonase-1(PON1) exhibits hydrolytic activity and prevents the oxidation of high and low-density lipoproteins. Polymorphisms in the PON1 gene have been associated with variations in paraoxonase activity and with the risk of coronary artery disease (CAD). AIM OF THE STUDY: This study analyzed the association between the frequencies of genotypes of the L55 M and Q192 R SNPs in the PON1 gene with the PON1 activity and with CAD risk factors. METHODS: Women, determined by body composition, biochemical markers, and arylesterase (AREase) and paraoxonase (CMPase) activities were studied. Genotyping of L55 M and Q192 R polymorphisms was performed by TaqMan. Seventeen studies were used in the meta-analysis. RESULTS: A significant decrease in PON1 activity in carrying the LM/MM and QQ genotypes is identified, correlations are found between the AREase activity with glucose, cholesterol and atherogenic risk index. Carriers of the LM or MM genotype were related with obesity (OR = 1.6; p = 0.039), and the MQ haplotype has an effect on the decrease in AREase (ß = â€’22.4; p <0.001) and CMPase (ß = â€’3.8; p <0.001). In addition, a lower proportion of Native American admixture was observed in women with LM or MM genotype, while it was higher for the European proportion compared with the LL genotype (p <0.001). CONCLUSIONS: The LL-L55 M and QR-Q192 R genotypes are identified as the most frequently in the different states or cities of the country, and genotypic proportions are different, probably depending on the genetic structure of the populations. The association that is reported more frequently in the different studies is with enzymatic activity.

Source apportionment of lead in the blood of women of reproductive age living near tailings in Taxco, Guerrero, Mexico: An isotopic study.

The concentration and isotopic composition of lead in the blood of forty seven women of reproductive age (15-45y) exposed to multiple sources in two rural communities of the mining region of Taxco, Guerrero in southern Mexico were determined in order to identify specific contributing sources and their apportionment and to trace probable ingestion pathways. Our data indicate that >36% of the studied women have blood lead concentrations above 10µgdL-1 and up to 87% above 5µgdL-1. Tailings contain between 2128 and 5988mgkg-1 of lead and represent the most conspicuous source in the area. Lead contents in indoor dust are largely variable (21.7-987mgkg-1) but only 15% of samples are above the Mexican Regulatory Guideline for urban soils (400mgkg-1). By contrast, 85% of glazed containers (range: 0.026-68.6mgkg-1) used for cooking and food storage are above the maximum 2mgL-1 of soluble lead established in the Mexican Guideline. The isotopic composition indicates that lead in the blood of 95% of the studied women can be modeled in terms of a mixing system between local ores (and derivatives), glazed pottery and Morelos bedrock, end-members, with the two former being largely the most important contributors. Only one sample shows influence of indoor paints. Indoor dust is dominated by ores and derivatives but some samples show evidence of contribution from a less radiogenic source very likely represented by interior paints. This study supports the application of lead isotopic ratios to identify potential sources and their apportionment in humans exposed to multiple sources of lead from both, natural and anthropogenic origin.

Methamidophos induces cytotoxicity and oxidative stress in human peripheral blood mononuclear cells.

Previous studies have shown that organophosphate pesticide (OP) exposure is associated with oxidative stress. Methamidophos (MET) is an OP widely used in agriculture, which is regarded as a highly toxic pesticide and it is a potent inhibitor of acetylcholinesterase. The aim of this study was to evaluate whether MET can induce oxidative stress at low concentrations in primary cultures of human peripheral blood mononuclear cells (PBMCs). PBMCs from healthy individuals were exposed to MET (0-80 mg/L) for 0-72 h. We performed the MTT and neutral-red assays to assess the cytotoxicity. As indicators of oxidative stress, the levels of reactive oxygen species (ROS) were assessed using flow cytometry, and the malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined. MET decreased the viability of PBMCs in a dose-dependent manner. At concentrations of 3, 10, or 20 mg/L for 24 h, MET increased the ROS production significantly compared with the vehicle control. Similarly, MET increased the levels of MDA at the same concentrations that increased ROS (10 and 20 mg/L); however, no changes in GSH levels were observed. These results suggest that MET increased the generation of oxidative stress in PBMCs. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 147-155, 2017.

Elevated Levels of LDL-C are Associated With ApoE4 but Not With the rs688 Polymorphism in the LDLR Gene.

INTRODUCTION: Apolipoprotein E (ApoE) 4 isoform has been associated with elevated levels of cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs), meanwhile several polymorphisms in the LDL receptor (LDLR) gene have been associated with increased levels of total cholesterol and LDL-C. MATERIAL AND METHODS: We studied 400 women from Southwest Mexico. Anthropometric features and biochemical profile were evaluated, and genotyping of single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene and rs688 in the LDLR gene was determined by TaqMan assays. RESULTS: We found significant association between LDL-C (odds ratio [OR] = 3.3, 95% confidence interval [CI]: 1.9-5.7) and marginal association with TG (OR = 1.7, 95% CI: 1.0-2.9) of atherogenic risk in women carriers of the ApoE4 isoform compared to ApoE3. The TT genotype of rs688 in the LDLR gene was not found to be associated with elevated levels of total cholesterol or LDL-C. CONCLUSION: Our results show that carrier women of the ApoE4 isoform are more likely to have elevated levels of LDL-C and therefore increased risk of developing atherosclerosis.

A permethrin/allethrin mixture induces genotoxicity and cytotoxicity in human peripheral blood lymphocytes.

Two pyrethroids, permethrin and allethrin, are often combined for large-scale use in public health programs to control vector-borne diseases. In this study, the genotoxic potential of a commercial formulation of permethrin and allethrin was examined using cultured human peripheral blood lymphocytes (PBL). Genotoxicity was evaluated using the cytokinesis-block micronucleus cytome (CBMN cyt) assay by measuring the frequency of micronuclei (MN), nuclear division index (NDI), formation of nucleoplasmic bridges (NPB) and nuclear buds (NBUD), as well as apoptotic and necrotic cells. Human PBL were treated with different concentrations of a permethrin/allethrin mixture (1/0.01, 5/0.07, and 10/0.14 µg/ml) for 24 or 36 h. The highest concentration (10/0.14 µg/ml) of permethrin/allethrin mixture significantly increased MN frequency and percent apoptotic cells after incubations for 24 or 36 h. The NDI was markedly decreased in response to treatment with 5/0.07 or 10/0.14 µg/ml permethrin/allethrin for both 24 and 36 h. Exposure to the permethrin/allethrin mixture did not significantly alter formation of NBUD, NPB, or percent necrotic cells. The MN frequency was significantly correlated with the number of apoptotic and necrotic cells but inversely correlated with NDI. Data demonstrated that a mixture of permethrin and allethrin induced concentration- and time-dependent cytotoxic and genotoxic damage to human PBL in vitro.

Maternal C677T MTHFR polymorphism and environmental factors are associated with cleft lip and palate in a Mexican population.

INTRODUCTION: Nonsyndromic cleft lip and cleft palate (CL/P) is associated with environmental, nutritional, and genetic factors. Maternal polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene have been associated with CL/P. OBJECTIVES: To determine the relationship between the risk of having a child with CL/P and maternal C677T and A1298C MTHFR polymorphisms, the intake of folate supplements, and exposure to environmental factors during the first trimester of pregnancy, a case-control study of Mexican mothers (88 case mothers and 116 control mothers) was conducted. METHODS: A questionnaire was used to assess exposure to environmental factors. The C677T and A1298C polymorphisms were identified by polymerase chain reaction with restriction fragment length polymorphism. RESULTS: Mothers with the 677CT or 677TT genotype had a higher risk of having a child with CL/P than mothers with the 677CC genotype (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1-5.7). An increased risk of having a child with CL/P was associated with the lack of folate supplementation during the first trimester of pregnancy (OR, 3.8; 95% CI, 1.9-7.6), and this risk was greater in the mothers with the 677TT or 677CT genotype than mothers who reported taking folate supplements and had the 677CC genotype (OR, 11.2; 95% CI, 3.3-37.5). Pesticide exposure was associated with CL/P. There was no significant association between either the A1298C variant or tobacco exposure and the risk of CL/P. CONCLUSION: These results suggest that gene-environment interactions play an important role in the development of CL/P.