Analysis of the of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. by PBET digestion in vitro/Caco-2 cell model and their cumulative risk assessment / 药学学报

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

Effect of co-exposure of low-level benzene derivatives and noise on hearing loss of workers / 中国职业医学

OBJECTIVE: To explore the effects of combined exposure to low-level benzene derivatives and noise on hearing loss of workers. METHODS: A total of 216 employees from nine wood furniture factories and four printing factories were selected as research subjects by typical sampling method. Those without exposure to occupational hazardous factors were set as the control group, those exposed to noise alone were set as the noise group, and those exposed to benzene derivatives and noise were set as the combined exposure group. The normalization of equivalent continuous A-weighted sound pressure level to a nominal 8 hours working day(L_(EX,8 h)) and the exposure concentration of time weighted average(C_(TWA)) of benzene, toluene, xylene, ethylbenzene in the workplace air of the three groups were detected, and the hearing threshold of 0.5-8.0 kHz in both ears of the research subjects were measured by pure tone audiometry. RESULTS: No benzene was detected in the workplace air of the combined exposure group, and the C_(TWA) of toluene, xylene and ethylbenzene were all lower than the occupational exposure limits. The L_(EX,8 h) of the noise group and combined exposure group were all higher than that of the control group [(85.6±2.5) vs(68.7±4.4) dB(A),(84.3±3.1) vs(68.7±4.4) dB(A), all P<0.05], while the L_(EX,8 h) of the noise group was higher than that of the combined exposure group [(85.6±2.5) vs(84.3±3.1) dB(A), P<0.05]. Compared with the control group, the individual frequency hearing thresholds, average hearing threshold of speech frequency and average hearing threshold of high frequency in both ears in the noise group and the combined exposure group were increased(all P<0.05), and the detection rates of speech frequency hearing loss and high frequency hearing loss were increased(all P<0.02). The hearing thresholds of right ear of 0.5, 1.0 kHz and left ear of 0.5 kHz were increased in the combined exposure group(all P<0.05), and the detection rate of speech frequency hearing loss was increased(16.7% vs 40.8%, P<0.02), when compared with the noise group. Multivariate logistic regression analysis results showed that the risk of speech frequency hearing loss and high frequency hearing loss in the combined exposure group were higher than that in the control group and the noise group(all P<0.05), after excluding the influence of confounding factors such as education level and smoking.CONCLUSION: The combined exposure to low-level benzene derivatives and noise may have a synergistic effect on the hearing loss in workers.

The effects of photoperiodism and exposure to bisphenol A on hepatic lipid metabolism in female mice / 中国职业医学

OBJECTIVE: To analyze the effects and the underlying mechanisms of photoperiodism and exposure to bisphenol A(BPA) on hepatic lipid metabolism in female mice. METHODS: A 2×2 factorial design was used. The photoperiod factor was set to fixed and shifted photoperiod, and the BPA factor was set to BPA exposure(BPA group) and non-exposure(control group). Specific pathogen free female C57 BL/6 J mice were randomly divided into four groups: fixed photoperiod control group, shifted photoperiod control group, fixed photoperiod BPA group, and shifted photoperiod BPA group, with eight rats in each group. The fixed photoperiod mice received a 12 ∶12 hours light-dark cycle, and the shifted photoperiod mice experienced reversed light-dark cycle once a week. Mice in BPA group were administered a dose of BPA 50 μg/kg body weigh by gavage, while mice in control group were given a equal volume of corn oil, once per day, five days per week for 12 weeks. The body weight of mice was measured during the experiment. After 12 weeks, all mice in each group were sacrificed. Plasma was collected and the levels of biochemical parameters were measured. Liver tissues were separated for examination of lipid deposition using oil red O and hematoxylin-eosin staining, and plasma triglyceride levels were measured. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA relative expression of genes of fat metabolism in liver tissues. RESULTS: At the end of the experiment, the body weights of mice were higher than that before the experiment(all P<0.05), but there was no statistically significant difference in body weights among the four groups(all P>0.05). The levels of plasma glucose, triglyceride and activity of alanine aminotransferase were higher in shifted photoperiod mice than that in the fixed photoperiod mice(all P<0.05). The plasma aspartate transaminase level was higher in BAP group than that in control group(P<0.01). The area of lipid staining in hepatic tissue was larger in the shifted photoperiod control group, fixed photoperiod BPA group and shifted photoperiod BPA group(all P<0.05), and hepatic lipid droplets aggregation was increased in these three groups compared with the fixed photoperiod control group. The mRNA relative expression of acetyl-coenzyme A carboxylase alpha(Acaca) was higher in the fixed photoperiod BPA and shifted photoperiod control groups(all P<0.05), compared with the fixed photoperiod control group. The relative expression of Acaca mRNA was lower in the shifted photoperiod BPA group than that in the fixed photoperiod BPA group(P<0.05). The mRNA relative expression of sterol regulatory element binding protein(Srebp) 1 and Srebp2 were significantly higher in the BPA group than that in the control group(all P<0.05). CONCLUSION: Both the single shifted photoperiod or BPA exposure can increase hepatic lipid deposition in female mice. The mechanism may be related to up-regulation of the mRNA expression of Acaca, Srebp1 and Srebp2. The shifted photoperiod in combination of BPA exposure has an antagonistic effect on the expression of Acaca mRNA in liver tissues of female mice.

Correlation between gut microbiota and neurological behavior in mice co-exposed to manganese and high-fat diet / 中国职业医学

OBJECTIVE: To investigate the effects of manganese(Mn) and high fat diet(HFD) co-exposure on the neurological behavior and gut microbiota in mice, and to observe the correlation between them. METHODS: Specific pathogen free adult male C57 BL/6 mice were randomly divided into 4 groups. Mice in control group and Mn exposure group were fed with normal diet, while the HFD group and co-exposure group were fed with HFD. Both the Mn exposure group and the co-exposure group were exposed to 10 mg/(kg·d) manganese chloride by intraperitoneal injection, while the control group and HFD group were treated with 0.9% sodium chloride solution of the same volume, once per day for 60 consecutive days. At the end of exposure, the mice were subjected to experiments of neurological behaviors. Then, the mice were sacrificed and intestinal feces were collected. The relative abundance of gut microbiota(relative abundance>1.000%) was detected by high-throughput sequencing. RESULTS: After exposure, the body weight of the HFD group and the co-exposure group increased significantly(P<0.05), while that of the Mn exposure group decreased(P<0.05), compared with the control group. The latency, time in central, crossing, total distance and open arm time(OT%) of mice in the Mn exposure group were lower than that of the control group(P<0.05), and close arm time(CT%) prolonged(P<0.05). Compared with the control group and the HFD group, the latency, rearing, time in central, crossing, total distance, OT% and open arm entry(OE%) of mice in the co-exposure group decreased(P<0.05), and CT% increased(P<0.05). The total distance of mice in the co-exposure group was lower than that of the Mn exposure group(P<0.05). The relative abundance of Firmicutes increased(P<0.05), those of Bacteroidetes and Actinobacteria decreased in mice in the HFD group at the phylum level(P<0.05) compared with mice in the control group. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria increased(P<0.05), and Bacteroidetes and Actinobacteria decreased(P<0.05) in mice in the Mn exposure group. The relative abundance of Oscillospira, Bacteroides and Prevotella of mice in the HFD group reduced at the genus level(P<0.05) compared with the control group. The relative abundance of Lactobacillus increased in Mn exposure group(P<0.05), and Oscillospira, Bacteroides and Prevotella decreased(P<0.05). The relative abundance of Firmicutes, Cyanobacteria and Lactobacillus of mice in the co-exposure group increased(P<0.05), and those of the remaining 6 bacteria were lower(P<0.05) compared with mice in the other 3 groups. Among the mice of co-exposure group, the latency was positively correlated with Bacteroidetes(P<0.05). The rearing was positively correlated with Firmicutes(P<0.05) and negatively correlated with Actinobacteria(P<0.01). The OE% was negatively correlated with Firmicutes(P<0.05) and positively correlated with Actinobacteria(P<0.05). The crossing was positively correlated with Prevotella(P<0.05). CONCLUSION: Manganese combined with HFD had a synergistic effect on the abnormality of neurological behavior of mice. There are some correlation between the abnormality of neurological behavior and the homeostatic imbalance of intestinal flora in mice.

Risk Factors Associated with Rhabdomyolysis in Acute Carbon Monoxide Poisoning

PURPOSE: The aim of this study was to determine the risk factors for rhabdomyolysis in patients with carbon monoxide (CO) poisoning. METHODS: This was a retrospective study on patients with CO poisoning who visited the emergency department from January 1, 2014 to December 31, 2015. We compared clinical variables between patients with and without rhabdomyolysis. RESULTS: Among 120 patients who were included to this study, 108 patients exhibited normal value of CPK (creatine phosphokinase), and 12 patients were diagnosed as rhabdomyolysis. Sources of CO, duration of CO exposure, initial GCS (Grasgow coma scale), initial systolic and diastolic blood pressure, initial body temperature and AKI (Acute kidney injury) were showed significant difference between patients who developed rhabdomyolysis and patients who did not. In addition, initial white blood cell counts, troponin I level and carboxyhemoglobin (COHb) level were more higher in rhabdomyolysis group. pH and initial bicarbonate level were more lower. Duration of CO exposure (Odds ratio, 1.011; 95% confidence interval, 1.002∼1.020, P=0.021)was found to be only risk factor for rhabdomyolysis by logistic regression analysis. CONCLUSION: Duration of CO exposure is potential risk factor of rhabdomyolysis development in CO poisoning.

Effects of fluoride and ethanol administration on lipid peroxidation systems in rat brain.

Exposure to fluoride and excessive ethanol consumption has been identified as a serious public health problem in many parts of the world, including India. Thus, the effect of co-exposure to fluoride and ethanol for 3-6 weeks was studied on lipid peroxidation (LPO) and oxidative stress related parameters in the rat brain. After 3 weeks, co-treated animals showed 95% increase in LPO levels compared to control. However, the levels of reduced glutathione, total and protein thiols were decreased. These changes were accompanied by a decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase. Rats exposed to fluoride together with ethanol for 6 weeks resulted in 130% increase in LPO and decrease in the reduced glutathione levels. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase were reduced under these conditions. Brain histology revealed excessive lymphocytes, edema and spongeosis in the cortical region after six weeks of fluoride and ethanol treatment. These results suggest that exposure to fluoride together with ethanol enhances lipid peroxidation by affecting antioxidant defence systems in the rat brain.