Chunhong Wang

Selection of Nutrients for Prevention or Amelioration of Lead-Induced Learning and Memory Impairment in Rats

BACKGROUNDnWe carried out animal experiments based on the orthogonal design L(8)(2(7)) setting seven factors with two different levels of each and 10 groups of rats. The nutrients tested were tyrosine, glycine, methionine, taurine, ascorbic acid, thiamine and zinc.nnnOBJECTIVESnThe objective of this study was to explore the optimal combinations of nutrients for prevention or amelioration of lead-induced learning and memory impairment.nnnMETHODSnRats were supplemented with nutrients by gavage once a day in two experiments: one was simultaneous nutrient supplementation with lead acetate administration (800 mg l(-1)) for 8 weeks (prophylactic supplementation) and the other was nutrient supplementation for 4 weeks after the cessation of 4 weeks of lead administration (remedial supplementation). Morris water maze was initiated at ninth week. Rats were terminated for assays of levels of Pb in blood, activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in hippocampus, levels of nitric oxide (NO) in hippocampus and expressions of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) response element-binding protein messenger RNA in hippocampus.nnnRESULTSnResults showed that in prophylactic supplementation, methionine, taurine, zinc, ascorbic acid and glycine were the effective preventive factors for decreasing prolonged escape latency, increasing SOD and NOS activities and NO levels in the hippocampus, respectively. On the other hand, in remedial supplementation, taurine was the effective factor for reversing Pb-induced decrease in activities of SOD, NOS and levels of NO.nnnCONCLUSIONSnIn conclusion, the optimum combinations of nutrients appear to be methionine, taurine, zinc, ascorbic acid and glycine for the prevention of learning and memory impairment, while taurine and thiamine appear to be the effective factors for reversing Pb neurotoxicity.

Blood lead levels of both mothers and their newborn infants in the middle part of China

A cross-sectional investigation on maternal and umbilical blood lead levels in an urban area, an industrial town and a rural area of middle China is reported. Blood samples from 89 mothers during delivery, from the umbilical cords and from 105 non-pregnant women were collected. Self-administered questionnaires including the medical history and the pregnancy-related complaints were performed. After acid digestion, the whole blood lead levels were determined by a 180-80 flame atomic absorption spectrometer. The geometric mean for lead levels in blood of non-pregnant women was 66.9 microg/l (range: 25.0-201.0 microg/l) in the urban, 66.9 microg/l (range: 30.5-198.8 microg/l) in the industrial town, and 53.3 microg/l (range: 16.0-170.5 microg/l) in the rural area. The geometric mean of lead levels in blood of pregnant women at delivery both in the rural area (74.4 microg/l, range: 35.2-245.6 microg/l) and industrial town (65.9 micro/l, range: 20.0-172.0 microg/l) were higher than in the urban region (54.3 microg/l, range: 27.9-187.0 microg/l; p < 0.05). Compared with non-pregnant women at the same area, the blood lead levels of pregnant women was lower in urban (p < 0.05), but higher in rural areas (p < 0.05). The geometric mean for lead level in umbilical cord blood was significantly higher in rural (84.1 microg/l, range: 28.0-185.0 microg/l) than in the other areas (53.5 microg/l, range: 23.5-156.7 microg/l in the urban; 60.1 microg/l, range: 12.5-168.3 microg/l in the industrial town). The total geometric mean for lead level in cord blood was 69.0 microg/l (range: 12.5-185.0 microg/l), and 17.8% samples were above the blood lead threshold of health concern (> or =100 microg/l) for children (CDC, 1991), but the body weight and length of newborn babies have not been affected. The correlation between maternal and cord blood was 0.6805 (p < 0.01). Most of the pregnant women did not take the calcium supplements recommended during pregnancy. In conclusion, there were some lead burdens on both the mothers and their newborn babies in these areas. All possible measures should be taken to reduce the environmental lead exposure. It is also crucial that maternal nutrient intake, particularly calcium, should be sufficient.

Methionine choline reverses lead-induced cognitive and N-methyl-d-aspartate receptor subunit 1 deficits.

The principal effects of Pb(2+) exposure in children are attention, memory and learning deficits that persist into adulthood. The application of the conventional chelators in children is somewhat prohibited by adverse health effects and is not effective in reversing learning deficits once they have occurred. In this study, we applied the nutrients, methionine and choline, to prevent Pb(2+)-induced cognitive impairment. Male weanling Sprague-Dawley rats were divided into five groups. Three groups of rats were exposed to Pb(2+) in drinking water containing 400mg/L Pb(2+) acetate, of which two groups were concurrently administered by oral gavage once a day, 6 days per week, with low or high doses of methionine and choline for 60 days. The normal control group received distilled water alone, and the reagent control received methionine choline chloride alone. Methionine choline treatment reversed long-term deficits in spatial learning and memory caused by Pb(2+) exposure in rats. Enhanced learning performance of Pb(2+)-exposed rats was associated with recovery of deficits in N-methyl-d-aspartate receptor (NMDAR) subunit 1 (NR1) mRNA and protein expression in the hippocampus. The effect of methionine choline on NR1 gene and protein expression was somewhat specific to Pb(2+)-exposed rats and did not affect the NR2A and NR2B subunits of the NMDAR measured in the same animals. Moreover, methionine choline treatment did not lower brain Pb(2+) content in Pb(2+)-exposed rats, although it reduced blood and bone Pb(2+) content. Methionine and choline reversed cognitive and NR1 deficits induced by Pb(2+) exposure, a beneficial effect that has significant clinical implications for the treatment of childhood Pb(2+) intoxication.

The vitamin D receptor Fok1 polymorphism and bone mineral density in Chinese children

BACKGROUNDnTo evaluate the relationship between vitamin D receptor (VDR) gene polymorphism and bone mineral density (BMD) in 213 healthy children aged 6-10 year in China.nnnMETHODSnA questionnaire survey of dietary pattern, outdoor activity was conducted among 213 children (boys 126, girls 86) randomly selected in Xishui county of Hubei province. The BMD was determined by dual energy X-ray absorptiometry at the distal forearm, calcium, phosphorus, and alkaline phosphatase in serum were immediately analyzed. The FokI polymorphism was detected by using PCR-RFLP.nnnRESULTSnBMD was significantly higher in boys than in girls in 8/9 year group. (2) the frequencies of FF, Ff, and ff genotype were 25.8%, 62.0% and 12.2%, respectively; no difference was found between boys and girls. (3) BMD of children carrying FF genotype was higher (0.256+/-0.03) than those of carrying Ff genotype (0.241+/-0.03), P<0.01; the Ff genotype was associated with lowest forearm BMD in both boys and girls. Outdoor activity also positively affected peak bone mass.nnnCONCLUSIONnThe Fok1 polymorphism of the VDR receptor seems to directly affect bone mineral mass in Chinese children.

Lead-induced ER calcium release and inhibitory effects of methionine choline in cultured rat hippocampal neurons

Lead, a ubiquitous neurotoxicant, can result in learning and memory dysfunction. Long term potentiation in the hippocampus, a potential neural substrate for learning and memory, is thought to be linked to calcium-triggered intracellular events. In this study, laser scanning confocal microscopy was used to examine the effects of Pb(2+) on intracellular and endoplasmic reticulum free calcium concentration ([Ca(2+)](i) and [Ca(2+)](ER)) in cultured neonatal rat hippocampal neurons and their possible antagonism by methionine choline; understanding these effects would help explain the lead-induced cognitive and learning dysfunction and explore efficient safety and relief strategies. The results showed that Pb(2+) increased [Ca(2+)](i) and decreased [Ca(2+)](ER) linearly in a time- and concentration-dependant manner, and Pb(2+) addition after the applying of a ryanodine receptor (RyR) antagonist and an inositol-1,4,5-triphosphate receptor (IP(3)R) antagonist did not increase [Ca(2+)](i). The addition of 10, 20, or 40 mmol/L methionine choline simultaneously with addition of 10 μmol/L Pb(2+) decreased [Ca(2+)](i) in Ca(2+)-free culture medium by 39.0%, 66.0%, and 61.6%, respectively, in a concentration-dependant manner in a certain dose range. Our results suggest that Pb(2+) induces ER calcium release to increase the resting [Ca(2+)](i); and methionine choline inhibit this increase in [Ca(2+)](i).

Cross-sectional study of cardiovascular effects of carbon disulfide among Chinese workers of a viscose factory

OBJECTIVEnThis cross-sectional study investigates the cardiovascular effects among Chinese workers who were occupationally exposed to carbon disulfide (CS2), and evaluates the protective value of the current Chinese Maximum Allowable Concentration (MAC) of CS2 against cardiovascular effects.nnnMETHODSnThe measurements of exposure were performed by personal sampling and gas chromatography. The biological monitoring was performed by HPLC. Three hundred and sixty-seven exposed workers and 125 reference workers (never exposed to CS2,) were included in this study. The exposed workers were divided into 2 sub-groups according to their cumulative exposure indices, the cut-off point being at 100 which means 10 years exposure to the Chinese Maximum Allowable Concentration in the workplace (10 mg/m3). All subjects were examined using a self-administered questionnaire including medical and job history, clinical complaints in the previous three months, and underwent a clinical check-up and a 12 lead electrocardiography (ECG) at rest, coded according to the Minnesota code. Blood pressure (BP) was recorded and blood samples were collected for lipid measurements.nnnRESULTSnThe personal monitoring showed that the exposures levels (15.47 +/- 2.34 mg/m3) were below the Threshold Limit Value (TLV, 31 mg/m3), and most of the samples analyzed still showed higher values than the Chinese MAC (10 mg/m3). Clinical complaints and abnormal electrocardiograms were not significantly increased in exposed workers. No significant effect of CS2 on blood pressure, cholesterol, HDL and LDL cholesterol or triglycerides was found. Further studies are recommended to elucidate the mechanism of cardiac intoxication after CS2 exposure.nnnCONCLUSIONnThis study showed that Chinese workers exposed to CS2 did not have more clinical complaints, nor more ECG abnormalities than controls and no adverse effects were found in their lipids at an exposure level below the current TLV. The present results indicate that differences of health effects reported worldwide are possibly due to different exposure levels. They also indicate that the current Chinese MAC (10 mg/m3) sufficiently protects workers against negative cardiovascular effects.

Carbon disulfide at a Chinese viscose factory external and internal exposure assessment.

This article presents the results of carbon disulfide exposure measurements in a Chinese viscose rayon factory. The objectives of the study were to identify the external exposure levels at a large factory and to investigate the 2-thiothiazolidine-4-carboxylic acid (TTCA) concentrations in the urine of the subjects who were exposed to carbon disulfide in the working place atmosphere. The metabolism of carbon disulfide in the exposed subjects was also studied in order to demonstrate the best points in time for the internal exposure sampling. The measurement of the amount of personal exposure to carbon disulfide in the air of the workplace was performed by GC-FPD; the presence of TTCA in the workers urine was analyzed by use of a modified HPLC method. The kinetics of TTCA excretion was studied by analyses at different time-points both during and after exposure to carbon disulfide in the subjects. A total of 155 personal samples were obtained. The carbon disulfide concentration in the staple viscose hall was 13.72 +/- 1.12 mg m-3 in terms of the geometric mean +/- geometric standard deviation, and was 20.05 +/- 1.33 mg m-3 in the filament spinning hall. The TTCA values in the subjects who worked in the staple spinning hall were 1.18 +/- 0.43 mg g-1 creatinine and 1.07 +/- 0.38 mg g-1 creatinine for subjects working in the filament spinning hall. The best time for TTCA sampling is at the end of the working shift, the TTCA excretion was stable for a period of 4-12 h after exposure of the subjects to the carbon disulfide. It might be that the Chinese have different anthropometric characteristics; a sampling bias may therefore appear among different races.

The role of PGC-1α and MRP1 in lead-induced mitochondrial toxicity in testicular Sertoli cells.

The lead-induced toxic effect on mitochondria in Sertoli cells is not well studied and the underlying mechanism is poorly understood. Here we reported the potential role of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and multidrug resistance protein 1 (MRP1) in lead acetate-induced mitochondrial toxicity in mouse testicular Sertoli cells TM4 line. We found that lead acetate treatment significantly reduced the expression level of PGC-1α, but increased the level of MRP1 in mitochondria of TM4 cells. To determine the role of PGC-1α and MRP1 in lead acetate-induced mitochondrial toxicity, we then generated PGC-1α stable overexpression and MRP1 stable knockdown TM4 cells, respectively. The lead acetate treatment caused TM4 cell mitochondrial ultrastructure damages, a decrease in ATP synthesis, an increase in ROS levels, and apoptotic cell death. In contrast, stably overexpressing PGC-1α significantly ameliorated the lead acetate treatment-caused mitochondrial toxicity and apoptosis. Moreover, it was also found that stably knocking down the level of MRP1 increased the TM4 cell mitochondrial lead-accumulation by 4-6 folds. Together, the findings from this study suggest that PGC-1α and MRP1 plays important roles in protecting TM4 cells against lead-induced mitochondrial toxicity, providing a better understanding of lead-induced mitochondrial toxicity.

Cross-sectional study of the ophthalmological effects of carbon disulfide in Chinese viscose workers

This article presents cross-sectional investigation results of ophthalmological effects for the occupational exposure to carbon disulfide of workers at a large viscose fibre factory in the middle part of China. The total of 271 exposed subjects (191 males, 80 females) and 133 workers (93 males, 40 females) not exposed to any toxic agent in the working environment underwent ophthalmological examination. The self-administered questionnaire collected data on the medical history and ophthalmological complaints during the past three months. The ophthalmologic examination included routine examination for retinal capillary anomalies and and color vision with the FM 100-Hue test method. Nearly all subjects did not use respirators, smocks or aprons, gloves or other personal protective devices during work time. The average personal CS2 exposure level in the present study was 13.7-20.05 mg/m3. The FM 100-Hue test results showed that the total error scores of the exposed group, whether male or female, were higher than that of the control, the discrimination of the green and blue zones was also impaired significantly. A fundus examination showed no retinal capillary anomalies or other serious ophthalmological symptoms that may be related to effects of CS2. In conclusion, color vision was disturbed in workers exposed to CS2, at levels below the present threshold value. Reduced color discrimination may be attributed to long-term carbon disulfide exposure and suggests that health surveillance of workers exposed to carbon disulfide should include the FM 100-Hue Test as a sensitive and easy method.

Heavy Metal Level in Human Semen with Different Fertility: a Meta-Analysis

There are conflicting reports on the heavy metal levels in human semen with different fertilities. The purpose of this analysis is to merge and analyze the differences of heavy metal lead (Pb), cadmium (Cd), zinc (Zn), and copper (Cu) levels in male semen with normal and low fertilities. All documents in both Chinese and English were collected from the PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) database from inception date to February 19, 2016. We have used RevMan software (version 5.2) for the meta-analysis and Stata software (version 12.0) for the meta-regression and sensitivity analyses. A total of 20 literatures were included in the study. The results of the meta-analysis indicate a significant difference between fertility with three metal ions (Pb, Cd, Zn) while no significant difference with copper, detailed as follows: (i) 10 studies on the lead concentrations with a standardized mean difference (SMD)xa0=xa02.07, 95 %CI (0.97, 3.17), Pxa0<xa00.01; (ii) 13 studies on the cadmium concentrations with an SMDxa0=xa00.75, 95 %CI (0.44, 1.07), Pxa0<xa00.01; (iii) 8 studies on the concentrations of zinc with an SMDxa0=xa0−0.61, 95 %CI (−1.08, −0.14), Pxa0<xa00.01; and (iv) 9 studies on the copper concentrations with an SMDxa0=xa00.42, 95 %CI (−0.29, 1.13), Pxa0=xa00.247. The results indicate that the men with low fertility have higher semen Pb and Cd levels and lower semen Zn levels; more studies are needed to indicate the association of the semen copper level with fertility.