Jiaohua Luo

Effects of arsenic exposure from drinking water on spatial memory, ultra-structures and NMDAR gene expression of hippocampus in rats

Epidemiological investigations indicate that chronic arsenic exposure can damage neurobehavioral function in children. The present study was aimed to study the effects of arsenic exposure from drinking water on the spatial memory, and hippocampal ultra-structures and N-methyl-d-aspartate receptor (NMDAR) gene expression in rats. Sprague-Dawley rats were assigned to four groups: rats in control group drank regular water, rats in other groups drank water with final arsenic concentration of 2.72 mg/L (group A), 13.6 mg/L (group B) and 68 mg/L (group C), respectively, for 3 months. The levels of arsenic in blood serum and hippocampus were monitored. Rats were tested in Morris water maze (MWM) for memory status. Samples of hippocampus were collected from two rats in each group for transmission electron microscopic study and the detection of NMDAR expression by RT-PCR. The rats in group C showed a significant delay in hidden platform acquisition. Neurons and endothelial cells presented pathological changes and the expression of NR2A was down-regulated in hippocampus in arsenic exposed rats. Our data indicated that arsenic exposure of 68 mg/L caused spatial memory damage, of which the morphological and biochemical bases could be the ultra-structure changes and reduced NR2A expression in hippocampus.

Phthalate Levels in Cord Blood Are Associated with Preterm Delivery and Fetal Growth Parameters in Chinese Women

Data concerning the effects of phthalate exposure on preterm delivery and fetal growth are limited in humans. In this paper, we assessed the relationship between 15 phthalate levels in cord blood and preterm delivery and fetal growth parameters in 207 Chinese women going into labor. Exposure to phthalates except DCHP was associated with gestational age reduction and preterm delivery (p<0.05). There were associations between phthalates and fetal growth parameters, many of which disappeared when analyses were adjusted for gestational age, especially in male infants (Only DEEP was associated with birth weight; DEP, DNHP, BBP, DNP with abdominal circumference; DEP, DBP, DCHP, DEHP with femur length in female infants. And DPP, DBEP was associated with birth length in male infants. p<0.05). This study indicates that prenatal exposure to phthalates is associated with younger gestational age and preterm delivery. Also, phthalate exposure may adversely affect fetal growth parameters via gestational age reduction and preterm delivery with a significant gender effect.

Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague-Dawley rats following combined oral exposure to benzo[a]pyrene and di-(2-ethylhexyl) phthalate

The aim of the present study was to determine the ovotoxicity of female Sprague-Dawley (SD) rats exposed to benzo[a]pyrene (B[a]P) and di-(2-ethylhexyl) phthalate (DEHP), either alone or in combination; the molecular mechanism and the combined effects were also evaluated. Female rats were given intragastric administration of control (corn oil), B[a]P (5 and 10mg/kg), DEHP (300 and 600 mg/kg) and B[a]P+DEHP (at 5mg/kg and 300 mg/kg respectively, or at 10mg/kg and 600 mg/kg respectively) on alternate days for 60 days. Relative ovary weight, estrous cycle, 17β-estradiol blood level, ovarian follicle populations, granulosa cell apoptosis, and gene and protein expression of P450Arom and PPAR were investigated. Our study demonstrated that the combination of B[a]P and DEHP exerts ovotoxicity in female rats and suppression of sex hormone secretion and homeostasis, which is associated with prolonged estrous cycles, decreases in ovarian follicle populations and granulosa cell apoptosis involving a PPAR-mediated signaling pathway of action of the two chemicals. In addition, based on qualitative assessment of the combined toxicity, no interaction effects were observed following combined B[a]P and DEHP administration.

Arsenite exposure altered the expression of NMDA receptor and postsynaptic signaling proteins in rat hippocampus.

Chronic arsenic exposure has an adverse effect on neurobehavioral function. Our previous study demonstrated an elevated arsenic level, ultra-structure changes and reduced NR2A gene expression in hippocampus, and impaired spatial learning in arsenite-exposed rats. The NMDA receptor and the postsynaptic signaling proteins CaMKII, postsynaptic density protein 95 (PSD-95), synaptic Ras GTPase-activating protein (SynGAP) and nuclear activated extracellular-signal regulated kinase (ERK1/2) play important roles in synaptic plasticity, learning and memory. We hypothesized that the above molecular expression changes may contribute to arsenic neurotoxicity. In present study, the expression of NMDA receptor and postsynaptic signaling proteins in hippocampus were evaluated in rats exposed to 0, 2.72, 13.6 and 68 mg/L sodium arsenite for 3 months. Decreased protein expression of NR2A, PSD-95 and p-CaMKII α in the hippocampus of arsenite-exposed rats was observed, while the expression of SynGAP, a negative regulator of Ras-MAPK activity, was increased when compared with the controls. Additionally, decreased p-ERK1/2 activity was found in the hippocampus of arsenite-exposed rats. These data suggest that altered expression of NMDA receptor complex and postsynaptic signaling proteins may explain arsenic-induced neurotoxicity.

Occurrence and potential health risk of Cryptosporidium and Giardia in the Three Gorges Reservoir, China.

The Three Gorges Reservoir (TGR) is the biggest lake in the world and a major water source in China. There is no information about occurrence and impact of Cryptosporidium and Giardia on the aquatic ecosystem. 61 surface water samples from 23 monitoring sites and 5 treated effluent samples were collected and analyzed. Cryptosporidium oocysts and Giardia cysts were found, respectively, in 86.4% and 65.2% of a total of 66 water samples, with high concentrations in treated effluent. The mean percent recovery was 29.14% for oocysts and 34.86% for cysts. A seasonal pattern was observed, with positive samples for Cryptosporidium more frequent in flood period and positive samples for Giardia more frequent in impounding period. Counts of enterococci, fecal coliforms and total coliforms, and turbidity were significantly associated with Cryptosporidium concentration in backwater (water in a main river which is backed up by the Three Gorges Dam) areas of tributaries but not Giardia. High associations were also found between oocyst and cyst in backwater areas of tributaries and cities. The risks of infection and illness due to water consumption in four different exposure routes were estimated. The results showed that swimming in the TGR has the highest infection risk with 1.39 × 10(-3) per time (95% confidence interval (CI): 0.05-600.3 × 10(-5)) for Cryptosporidium and 2.08 × 10(-4) per time (95% CI: 0.05-878.87 × 10(-6)) for Giardia, while directly drinking unboiled tap water treated with the conventional process has the highest morbidity with 524.98 per 100,000 population per year (95% CI: 10.35-2040.26) for Cryptosporidium and 5.89 per 100,000 population per year (95% CI: 0.08-22.67) for Giardia. This study provides new useful information for drinking water plants, health care workers and managers to improve the safety of tap water and deduce the risk of surface water contamination in China.

Determination of Environmental Exposure to Microcystin and Aflatoxin as a Risk for Renal Function Based on 5493 Rural People in Southwest China.

Although the nephrotoxicity of microcystin and aflatoxin has been observed in animal and clinical cases, few population data are available. We conducted a cross-sectional study in Southwest China to investigate the association of renal function indicators (RFIs, including BUN, SCr, and eGFR) with exposure to microcystin and aflatoxin in 5493 members of the general population. Microcystin-LR levels in water and aquatic products and aflatoxin B1 levels in daily foods were measured by ELISA, and individual estimated daily intake (EDI) was assessed on the basis of the measurement and questionnaire. We found that participants with abnormal RFIs had a much higher mean level of microcystin-LR EDI than those with normal RFIs and that there was a significant increasing trend for abnormal rates and odds ratios of RFIs with increasing microcystin-LR EDI quartiles (p for trend = 0.000). Compared with the lowest quartile of microcystin-LR exposure, those in the highest quartile had significantly higher risks of abnormal BUN (OR = 1.80, 95% CI = 1.34-2.42), SCr (OR = 4.58, 95% CI = 2.92-7.21), and eGFR (OR = 4.41, 95% CI = 2.55-7.63), respectively, but no higher risk was found in subjects with higher AFB1 exposure. After adjustment for confounding factors, risk associations with microcystin-LR persisted. Consequently, our results suggest that microcystin, rather than aflatoxin, might be one important risk of renal-function impairment.

Maternal and early life arsenite exposure impairs neurodevelopment and increases the expression of PSA-NCAM in hippocampus of rat offspring

Although epidemiological investigations indicate that chronic arsenic exposure can induce developmental neurotoxicity in children, the molecular mechanisms are still poorly understood. Neural cell adhesion molecules (NCAMs) play critical roles during the development of nervous system. Polysialylation of NCAM (PSA-NCAM) is a critical functional feature of NCAM-mediated cell interactions and functions. The present study aimed at investigating the effects of maternal and early life arsenite exposure on NCAM and PSA-NCAM in rat offspring. To this end, mother rats were divided into three groups and exposed to 0, 2.72 and 13.6mg/L sodium arsenite, respectively, during gestation and lactation. After weaning, rat offspring drank the same solution as their mothers. Neural reflex parameters, arsenic level of hippocampus, ultra-structural changes of hippocampus, the expression of NCAM, PSA-NCAM and two polysialyltransferases (STX and PST) in rat offspring were assessed. Arsenite exposure significantly prolonged the time of completing reflex response of surface righting, negative geotaxis and cliff avoidance of rat offspring in 13.6mg/L As-exposed group. Neurons and capillaries presented pathological changes and the expression of NCAM, PSA-NCAM, STX and PST were up-regulated in hippocampus of rat offspring exposed to arsenite. These results indicated that maternal arsenite exposure increases the expression of PSA-NCAM, NCAM and polysialyltransferases in hippocampus of rat offspring on postnatal day (PND) 21 and PND120, which might contribute to the impaired neurodevelopment following arsenite exposure.

The XRCC1 Arg194Trp polymorphism is not a risk factor for glioma: A meta-analysis involving 1,440 cases and 2,562 controls.

Previous reports have indicated that the X-ray repair cross-complementing gene 1 (XRCC1) Arg194Trp polymorphism may be a risk factor for several types of cancer. Published studies on the association of XRCC1 Arg194Trp polymorphisms with glioma risk have yeilded conflicting results. The present study aimed to obtain a more precise estimation of this association. Meta-analyses assessing the association of the XRCC1 Arg194Trp variation with glioma were conducted and subgroup analyses based on ethnicity and source of controls were also performed. Eligible studies were identified during the period before May 2012. A total of four case-control studies comprising 1,440 cases and 2,562 controls were finally selected for analysis. The overall data failed to indicate a significant association of the XRCC1 Arg194Trp polymorphism with glioma risk [Trp vs. Arg: odds ratio (OR) = 1.01, 95% confidence interval (95% CI) = 0.77–1.33; Trp/Trp vs. Arg/Arg: OR = 1.56, 95% CI = 0.96–2.54; dominant model: OR = 0.98, 95% CI = 0.74–1.31; recessive model: OR = 1.48, 95% CI = 0.92–2.38]. Similarly, in the subgroup analysis based on ethnicity and source of controls, no associations were observed. In conclusion, the results of the present study failed to suggest an association between the XRCC1 Arg194Trp polymorphism and glioma risk. Further large and well-designed studies are required to confirm this conclusion.

Serum microcystin levels positively linked with risk of hepatocellular carcinoma: A case‐control study in southwest China

Microcystins have been reported to be carcinogenic by animal and cell experimentation, but there are no data on the linkage between serum microcystins and hepatocellular carcinoma (HCC) risk in humans. We conducted a clinical case‐control study to investigate the association between serum microcystins and HCC risk after controlling several known risk factors, such as hepatitis B virus, alcohol, and aflatoxin. From December 2013 to May 2016, 214 patients newly diagnosed with HCC along with 214 controls (frequency‐matched by age and sex) were recruited from three hospitals in Chongqing, southwest China. Basic information on lifestyle and history of disease was obtained by questionnaire. Blood samples were collected and analyzed for serum microcystin‐LR (MC‐LR) and aflatoxin‐albumin adduct by enzyme‐linked immunosorbent assay and for hepatitis B surface antigen status by chemiluminescence assay. Binary logistic regression analyses were performed to assess the independent effects of MC‐LR and its joint effects with other factors on HCC risk. The adjusted odds ratio for HCC risk by serum MC‐LR was 2.9 (95% confidence interval [CI], 1.5‐5.5) in all patients. Notably, a clear relationship between increased MC‐LR level (Q2, Q3, and Q4) and HCC risk was observed with elevated adjusted odds ratios (1.3, 2.6, and 4.0, respectively). Positive interactions with the additive model were investigated between MC‐LR and hepatitis B virus infection (synergism index = 3.0; 95% CI, 2.0‐4.5) and between MC‐LR and alcohol (synergism index = 4.0; 95% CI, 1.7‐9.5), while a negative interaction was found between MC‐LR and aflatoxin (synergism index = 0.4; 95% CI, 0.3‐0.7). Additionally, serum MC‐LR was significantly associated with tumor differentiation (r = –0.228, P < 0.001). Conclusion: We provide evidence that serum MC‐LR was an independent risk factor for HCC in humans, with an obvious positive interaction with hepatitis B virus and alcohol but a negative interaction with aflatoxin. (Hepatology 2017;66:1519–1528)

The consumption of low-mineral bottled water increases the risk of cardiovascular disease: An experimental study of rabbits and young men

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