Melatonin therapy reverses lead exposure-induced testicular damage in rats despite the lack of effect on serum testosterone levels.

Lead (Pb) exposure induces testicular damage and infertility. The aim of this study was to analyze and compare the therapeutic effects of antioxidants or vitamin D and calcium, which have previously been shown to reduce the toxic effects of Pb co-exposure, in rats. Rats were exposed to Pb for 28 days and subsequently treated with antioxidant (melatonin, silymarin), vitamin D and calcium (VitDCa) or a combination (melatonin or silymarin with VitDCa) for 28 days. Control groups included untreated rats (no Pb exposure or therapy), rats exposed only to melatonin or silymarin and rats exposed to Pb without post exposure therapy. Pb exposure induced testicular damage, increased blood lead level (BLL) and reduced serum testosterone level (STL). Rats exposed to Pb and left untreated for 28 days showed persistent pathological testicular alterations. The two treatments that were most effective in reversing pathological testis damage and restoring spermatogenesis were melatonin and silymarin. However, silymarin and melatonin treatment resulted in significantly different serum testosterone levels in rats. Whereas melatonin therapy reduced serum testosterone to levels lower than those in control rats, silymarin increased serum testosterone to levels higher than those in controls. Our pathological analysis of testes revealed that melatonin promoted spermatogenesis and regression of Pb exposure-induced degenerative changes, despite the associated reduction in serum testosterone levels. This result suggests that circulating testosterone may not have an important role in spermatogenesis. Collectively, our results suggest that melatonin and silymarin are effective therapies against the toxic effects Pb exposure in the male reproductive system.

Association of Dietary Advanced Glycation End Products with Metabolic Syndrome in Young Mexican Adults.

Background: Consumption of dietary advanced glycation end products is linked to metabolic syndrome. The objective was to describe the association between dietary advanced glycation end products intake and metabolic syndrome in young Mexican adults. Methods: The present was a cross-sectional study in 126 Mexican adults 18⁻35 years old evaluating metabolic syndrome through the harmonized criteria. Macronutrients and dietary advanced glycation end products intake were estimated through three 24-hour dietary recalls and food composition tables. Association between metabolic syndrome and high advanced glycation end products intake (≥10,000 kU/day) was evaluated through three logistic regression models adjusted by sex, age, family history of cardiometabolic diseases and energy intake. Results: Subjects with a higher advanced glycation end products intake were more likely to have impaired fasting glucose (OR: 4.91, 95% CI 1.29⁻18.60, p < 0.05) and metabolic syndrome (OR: 2.67, 95% CI 0.96⁻7.44, p = 0.059) than those participants with low consumption of these products after adjustment of sex, age, family history of cardiovascular disease and energy intake. Conclusions: High intake of dietary advanced glycation end products was significantly associated with impaired fasting glucose and marginally with metabolic syndrome in young Mexican adults regardless of sex, age, family history of cardiovascular disease and energy intake.

Environmental Epigenetic Changes, as Risk Factors for the Development of Diseases in Children: A Systematic Review.

BACKGROUND: Children are susceptible to environmental contaminants and are at risk of developing diseases, more so if the exposure begins at an early age. Epidemiological studies have postulated the hypothesis of the fetal origin of disease, which is mediated by epigenetic changes. Epigenetic marks are inheritable; they modulate the gene expression and can affect human health due to the presence of environmental factors. OBJECTIVE: This review focuses on DNA-methylation and its association with environmental-related diseases in children. METHODS: A search for studies related to DNA-methylation in children by pre- or post-natal environmental exposures was conducted, and those studies with appropriate designs and statistical analyses and evaluations of the exposure were selected. FINDINGS: Prenatal and early life environmental factors, from diet to exposure to pollutants, have been associated with epigenetic changes, specifically DNA-methylation. Thus, maternal nutrition and smoking and exposure to air particulate matter, polycyclic aromatic hydrocarbons, arsenic, heavy metals, persistent organic pollutants, and some endocrine disrupters during pregnancy have been associated with genomic and gene-specific newborns' DNA-methylation changes that have shown in some cases sex-specific patterns. In addition, these maternal factors may deregulate the placental DNA-methylation balance and could induce a fetal reprogramming and later-in-life diseases. CONCLUSIONS: Exposure to environmental pollutants during prenatal and early life can trigger epigenetic imbalances and eventually the development of diseases in children. The integration of epigenetic data should be considered in future risk assessments.

Preliminary human health risk assessment of arsenic and fluoride in tap water from Zacatecas, México.

Zacatecas state is located in the central area of Mexico, where the underground water contains elevated quantities of natural arsenic and fluoride. In order to estimate health risk associated with human exposure to these pollutants, tap water samples from the southern-central region of the state were analyzed. Ninety percent of the samples exceeded the levels of arsenic established by the World Health Organization (WHO) of 0.01 mg/L and 43 % exceeded the limit established by the NOM-127-SSA1(1) of 0.025 mg/L. Forty-three percent of the samples had fluoride levels above the Mexican regulation limit of 1.5 mg/L (NOM-127-SSA1). We used WHO and EPA's health risk assessment method, we estimated 80 % of the inhabitants of sites studied could be exposed to arsenic levels higher than those recommended by EPA and the WHO, 22 % could be exposed to fluoride levels higher than those recommended by EPA, and 16 % of the local population may be in risk of suffering dental fluorosis.

Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis PotosÍ and León, México.

This research was designed to analyze the possible associations of Arg389Gly ADRB1 and Trp64Arg ADRB3 polymorphisms in children with obesity. A cross-sectional study included 1,046 school-age Mexican participants (6-12 years old) from the cities of San Luis PotosÍ and León. Children were classified as non-obese or obese according to their body mass index (BMI) percentile; obese children had a BMI≥95th percentile for sex and age. Biochemical data were collected. Polymorphisms were detected using TaqMan qPCR assay. A logistic regression analysis was used to calculate the risk of obesity based on genotypes. Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, LDL-cholesterol, triglycerides, and lower HDL-cholesterol compared with the normal weight group (P<0.05). The distribution of allele frequency in the population was Arg= 87.4 and Gly= 12.6 (Hardy Weinberg equilibrium c2 = 3.16 , P = 0.07 ); Trp= 81.5 and Arg= 18.5 (Hardy Weinberg equilibrium c2 = 2.2, P = 0.14 ) for ADRB1 and ADRB3, respectively. Even though no different frequencies of Arg389Gly polymorphism between groups were found (P = 0.08), children carriers of one Gly389 ADRB1 allele had a risk for obesity of OR=1.40 (95%CI, 1.03-1.90, P = 0.03) after adjustment for age and gender. No other association was found for Trp64Arg ADRB3 polymorphism. Only the Arg389Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

Mechanisms of p,p'-DDE-induced apoptosis in human peripheral blood mononuclear cells.

p,p'-Dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of organochlorine insecticide p,p'-dichlorodiphenyltrichloroethane (DDT), has been detected in human populations living in malaria-endemic areas of México where this insecticide was used. DDE induces apoptosis in peripheral blood mononuclear cells (PMBC); however, the molecular mechanism of cell death induced by this compound is poorly understood. In the present study, PBMC isolated from healthy individuals (not exposed to DDE) were incubated in the presence of increasing concentrations of p,p'-DDE (0-80 microg/ml) over time. When PBMC were treated with low p,p'-DDE concentration (10 microg/ml) an antioxidant response and biomarkers of inflammation were induced, indicating a pro-inflammatory state. Moreover, when PBMC were treated with high p,p'-DDE concentration (80 microg/ml) several apoptotic biochemical events were triggered, such as activation of caspase-8, Bid, caspase-9 and caspase-3, as well as degradation of PARP and ubiquitination. The results described in this study show a possible inflammatory condition and the involvement of both extrinsic and intrinsic pathways in the induction of apoptosis in DDE-treated PBMC.

Indoor air pollution in a Mexican indigenous community: evaluation of risk reduction program using biomarkers of exposure and effect.

Indoor air pollution can be an important risk factor for human health, considering that people spend more than 60% of their time indoors. Fifty percent of the world population and approximately 90% of the rural population in developing countries are using biomass as energy source. Latin America represents 12% of the global consumption of biomass; in Mexico, 27 million people use wood as an energy source. Therefore, in this study we evaluated a 3-stage risk reduction program. The stages were: 1) removal of indoor soot adhered to roofs and internal walls; 2) paving the dirt floors; and 3) introduction of a new wood stove with a metal chimney that expels smoke outdoors. The complete intervention program was applied. In 20 healthy subject residents from an indigenous community in San Luis Potosí, Mexico, we measured blood carboxyhemoglobin (% COHb), DNA damage (comet assay) in nucleated blood cells, and urinary 1-OHP levels before and after the program. Before intervention individuals had a geometric mean COHb level of 4.93% and 53% of the population presented levels above 2.5% considered a safe level. However, in all the studied individuals the levels of COHb were reduced to below 2.5% (mean level 1.0%) one month after the intervention. Moreover, when compared, DNA damage in people exposed before the intervention was higher (5.8+/-1.3 of Tail Moment) than when the program was introduced (2.8+/-0.9 of Tail Moment) (P>0.05) and a same trend was observed with urinary 1-OHP levels; 6.71+/-3.58 micromol/mol creatinine was the concentration before intervention; whereas, 4.80+/-3.29 micromol/mol creatinine was the one after the program. The results suggest that the intervention program offers an acceptable risk reduction to those families that use biomass for food cooking.