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Background As a group of environmental pollutants, polycyclic aromatic hydrocarbons (PAHs) are neurotoxic and may cause mild cognitive impairment (MCI) by inducing inflammation. Whether neutrophil-lymphocyte ratio (NLR), an inflammatory indicator, plays a mediating role in the relationship between PAHs exposure and MCI is unclear yet. Objective To investigate a potential mediating role of NLR in the association between exposure to PAHs and MCI in coke oven plant workers. Methods Eleven urine hydroxylated PAHs (OH-PAHs) of 530 coke oven plant workers were determined by high performance liquid chromatography tandem mass spectrometry. NLR was derived from participants' routine blood examination results using a fully automated haematology analyser. The associations between urinary OH-PAHs and MCI were analyzed by binary logistic regression, the associations between urinary OH-PAHs and NLR were analyzed by multiple linear regression, and the role of NLR in the relationship between urinary OH-PAHs and MCI was evaluated by mediating effect analysis. Results After controlling for confounding factors and other OH-PAHs, the results of binary logistic regression showed that for every e-fold (e is the base of the natural logarithm) increase in the concentration of 2-hydroxynaphthalene (2-OHNap) and 1-hydroxyphenanthrene (1-OHPhe), the OR (95%CI) values of reporting MCI positive were 1.21 (1.02, 1.43) and 1.25 (1.04, 1.51) respectively. For each unit increase of NLR, the OR (95%CI) of reporting MCI positive was 1.56 (1.12, 2.18). The results of multiple linear regression showed that each unit increase in natural log-transformed levels of 1-OHPhe was associated with 0.05 (95%CI: 0.01, 0.10) increase of NLR. The results of mediating effect analysis showed that the association between urinary 1-OHPhe and MCI was partially mediated by peripheral blood NLR, with a mediation ratio of 9.8%. Conclusion Exposure to PAHs in coke oven plant workers may increase the risk of reporting MCI positive partially through increased NLR in peripheral blood.
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Background As a complex organic pollutant, polycyclic aromatic hydrocarbons (PAHs) exposure shares the common exposure characteristics of multiple hydroxyl metabolites. Most studies have analyzed independent effect of each PAHs metabolite and have adjusted for the potential confounding effects induced by other metabolites concomitantly, without considering possible interactions among them. Proper statistical methods are needed to study their toxic effects. Objective To explore the applicability of logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) in evaluating the correlation between mixed exposures to exogenous chemicals and health outcomes, compare the advantages and limitations of the three models, and propose analytical strategies for evaluating the health effects of mixed chemical exposure for application in the analysis of the association between PAHs exposure and cognition. Methods Urine samples were collected of workers from a coke oven plant and a water treatment plant in Shanxi Province, who participated in their routine employee healthexamination. Mono-hydroxylated PAHs were detected by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). A cut-off value of MoCA less than 26 was considered mild cognitive impairment (MCI). According to a predetermined inclusion and exclusion criteria, 1 051 cases were included in the final data analysis. Logistic regression, WQS regression, and BKMR were used to analyze the relationship between PAHs metabolites and MCI. Results The prevalence rate of reporting MCI among the 1 051 workers was 21.7% (228/1 051). The concentration of 2-hydroxynathalene (2-OHNAP) was the highest among the 11 PAHs metabolites with a median concentration of 0.30 μg·L−1, followed by 9-hydroxyphenanthrene (9-OHPHE) (0.26 μg·L−1). There were significant differences between the two groups in 2-OHNAP, 1-hydroxynaphthalene (1-OHNAP), 2-hydroxyfluorene (2-OHFLU), 9-OHPHE, 1-hydroxyphenanthrene (1-OHPHE), and 1-hydroxypyrene (1-OHPYR) (all Ps<0.05). In the logistic regression, 2-OHNAP and 2-OHPHE were associated with MCI, and the OR (95%CI) for reporting MCI was 1.28 (1.01-1.67) and 1.27 (1.00-1.72) for each 10-fold increase in 2-OHNAP and 2-OHPHE concentrations, respectively. In the WQS regression analysis, the WQS index was positively correlated with the prevalence rate of reporting MCI (OR=1.37, 95%CI: 1.10-1.72). In the BKMR analysis, compared with the median exposure levels of all chemicals, the overall effect was statistically significant when all PAHs metabolites concentrations were at or above their 30th percentile; when all exposures were at the 75th percentile, the risk of reporting MCI increased by 6%. Conclusion Based on the results of these three models, 2-OHNAP and 2-OHPHE are the most important factors related to cognitive. It is recommended to use a combination of traditional logistic regression and either WQS or BKMR to study the association between PAHs and MCI.
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OBJECTIVE: To explore the relationship between maternal polycyclic aromatic hydrocarbons( PAHs) exposure during pregnancy and neonatal neurobehavioral development. METHODS: A total of 296 pairs of pregnant women and their newborns in hospital A in Changzhi City and hospital B in Taiyuan City were selected as research subjects by convenience sampling method. The air PAHs levels in these two hospitals were measured using high performance liquid chromatography( HPLC). The pregnant women were investigated by questionnaires. The levels of PAHs metabolites in prenatal 24-hour urine samples were measured as indicators of exposure using HPLC. The pregnant women were divided into PAHs low-,medium-and high-exposure groups based on the 25th and the 75th percentile levels. The neonatal birth weight,head circumference and birth length were measured,and the neonatal neurobehavioral development was measured by neonatal behavioral neurological assessment( NBNA). RESULTS: The median level of total PAHs metabolite in maternal urine was 0. 94 mg/mo L creatinine. The newborn total NBNA scores,behavioral abilities and active muscle tension scores in the PAHs high-exposure group were lower than that of PAHs low-and medium-exposure groups( P < 0. 05). The newborn total NBNA scores and active muscle tension scores in the PAHs medium-exposure group were lower than that of PAHs lowexposure group( P < 0. 05). There was no significant difference in scores of neonatal weight,head circumference,birth length,passive muscular tension,primary reflexes and general reaction among these three groups( P > 0. 05). The multiple stepwise linear regression analysis results showed that the level of PAHs metabolite in maternal urine were negatively correlated with the total NBNA scores,behavioral abilities score,active muscle tension scores and general reaction score( P < 0. 05),and showed no correlation with the neonatal birth weight,head circumference,passive muscular tension score,birth length and primary reflexes scores( P > 0. 05). CONCLUSION: The level of total PAHs metabolites in maternal prenatal urine is associated with neonatal neurobehavioral development. This result indicates that maternal PAHs exposure during pregnancy may have adverse effects on neonatal neurobehavioral development.
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OBJECTIVE: To explore the effects of sub-chronic aluminum exposure on the combination of hippocampus neuroligin 1( NL1) with N-methyl-D-aspartate receptor( NMDAR) and the effects of correlated bonding to long-term potentiation( LTP) in rats. METHODS: Ninety healthy male specific pathogen free SD rats were selected and randomly divided into blank control group,solvent control group and low-,medium-and high-dose groups,with 18 rats in each group. The rats in blank control group received no treatment. Rats in solvent control group were given 0. 9% sodium chloride solution by concentration of 1 m L/kg body weight( bw). The low-,medium-and high-dose group rats were given the mass concentration of 0. 41,0. 81,1. 62 mg/kg bw maltol aluminum solution by intraperitoneal injection every other day for 1,2,and 3 months,respectively. After maltol aluminum exposure,LTP was detected in the CA1 region of rat hippocampus,aluminum levels were detected by the graphite furnace atomic absorption spectrometry,and the protein relative expression of NL1 combined with NMDAR1 and NMDAR2B were detected by immunoprecipitation and immunoblotting. RESULTS: The LTP in the solvent control group and the low-,medium-,high-dose groups were all lower than that in the blank control group( P < 0. 01). The LTP in the high-dose group was lower than those in the solvent control group and the low-and medium-dose groups( P < 0. 05). The aluminum levels in the hippocampus of rats in the low-,medium-and high-dose groups were higher than those of the blank control group and the solvent control group( P <0. 01). The protein relative expression of NMDAR1 and NMDAR2B combined with NL1 in treatment groups was lower than those in the blank control group and solvent control group at the same exposure time points( P < 0. 01). The protein relative expression of NMDAR1 and NMDAR2B combined with NL1 in treatment groups at time point of 2 months was lower than those at time point of 1 month in the same dose group( P < 0. 01). The protein relative expression of NMDAR1 and NMDAR2 B combined with NL1 at time point of 3 months was lower than those at time points of 1 and 2 months in the same dose group( P < 0. 01). CONCLUSION: Maltol aluminum can prevent the normal combination of NL1 with NMDAR1 and NMDAR2B,affecting LTP regulated by NMDAR1 and NMDAR2B,resulting in a LTP decline,as well as learning and memory impairment.
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OBJECTIVE: To study effects and mechanism of sub-chronic aluminum-maltolate complex [Al( mal)3]exposure on mitochondrial damage of hippocampus in rats. METHODS: Sixty specific pathogen free healthy adult male SD rats were randomly divided into 5 groups: a blank group,a control group,a low-,a medium- and a high-dose group,with 12 rats in each group. Blank group was not treated. Low-,medium- and high-dose groups were treated with 0. 41,0. 81,1. 62 mg / kg body weigh of Al( mal)3solution respectively. The control group was treated with an equal volume of saline. Al( mal)3exposure was conducted by intraperitoneal injection every other day for 90 days. The activities of Na+-K+-ATPase and Ca2 +-Mg2 +-ATPase in hippocampus were tested by chemical colorimetric technique. Western blot analysis was used to detect the relative expression of cytochrome oxidase Ⅳ( Cox Ⅳ),dynamin-related protein 1( Drp1),optic Atrophy 1( Opa1),mitofusin( Mfn) 1,and Mfn2 in hippocampus. RESULTS: The activity of Na+-k+-ATPase in high-dose group was significantly lower than those in blank-,control-,and low-dose groups( P < 0. 05). The activity of Ca2 +-Mg2 +-ATPase in medium-dose group was significantly lower than those in blank group( P < 0. 05),and that in high-dose group was significantly lower than those in the other four groups( P < 0. 05). The relative expression levels of CoxⅣ in mediumand high-dose groups were lower than those of the other three groups( P < 0. 05). The relative expression levels of Drp1 and Mfn2 in medium-and high-dose groups were significantly higher than those in blank-,control and low dose group( P <0. 05). The relative expression levels of Opa1 in medium- and high-dose groups were significantly higher than those in blank-,control- and low-dose groups( P < 0. 05). The relative expression levels of Mfn1 in medium- and high-groups were significantly higher than that in blank group( P < 0. 05). CONCLUSION: The mitochondria of rat hippocampus was damaged by the sub-chronic aluminum-maltolate exposure. The damage may be related to the change of mitochondrial dynamics.
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Objective To investigate the changes and mechanism of learning and memory in rats by different doses of benzo (a) pyrene (B(a)P). Methods Forty weaned rats (28 days) were randomly divided into control group (NS), solvent group ( vegetable oil) and three B (a) P dosage groups (the doses were 5,10 and 20 mg / kg body weight respectively ). And all rats were administrated intraperitoneally every other day to one month. The capability of learning and memory in rats were measured by Morris water maze test, and the brain-derived neurotrophic factor ( BDNF) and NMDAR2B content in hippocampus were tested by immunohistochemistry. Results In training of Morris water maze,the average escape latency was extended gradually with increasing dose, and there was a statistically significant difference between high-dose group((62. 78 ±47. 25 )s) and the control group((40.60±38.79)s)(P＜ 0.01). Compared with the control group(11.25 ±2.63), the number of crossplatform of high-dose group(4.33 ±2.08) was statistically reduced (P＜0.05). B(a)P at 10 and 20 mg/kg decreased NMDAR2B and BDNF expression in hippocampus of rats in immunohistochemistry. The level of NMDAR2B was (162.23 ±6.56) in the high-dose group and (150.38 ± 15.34) in the control group(P＜0.05);the expression level of BDNF was (163. 13 ± 8.09) in the high-dose group and (141.83 ± 13.37) in the control group(P＜ 0.05). Conclusion Subacute B(a)P exposure can reduce spatial learning and memory in weaning rats, it may be related to decreased levels of NMDAR2B and BDNF in hippocampus.