Roles of oxidative stress, apoptosis, and heme oxygenase-1 in ethylbenzene-induced renal toxicity in NRK-52E cells.

Ethylbenzene is an important industrial chemical, but its potential toxicity is a recent concern. Our previous study investigated the renal toxicity of ethylbenzene in vivo Rat renal epithelial cells (NRK-52E cells) were incubated with 0, 30, 60, and 90 µmol/L of ethylbenzene for 24 h in vitro to investigate ethylbenzene-induced oxidative stress, apoptosis, and the expression of heme oxygenase 1 (HO-1) and nuclear factor (erythroid 2)-related factor 2 (Nrf2). The cell survival rate in the ethylbenzene-treated groups was significantly lower than the control group. Ethylbenzene significantly increased intracellular reactive oxygen species and apoptosis. Malondialdehyde levels were significantly elevated compared with the control group, while glutathione levels and glutathione peroxidase activities were decreased in ethylbenzene-treated groups. The activities of catalase and superoxide dismutase were also markedly reduced. A significant dose-dependent increase in HO-1 and Nrf2 messenger RNA expression levels was observed in ethylbenzene-treated groups compared with the control group. Similarly, ethylbenzene treatment enhanced protein expression of HO-1 and Nrf2 in a dose-dependent manner. Our results indicated that ethylbenzene induced oxidative stress, apoptosis, and upregulation of HO-1 and Nrf2 in NRK-52E cells, which contributes to ethylbenzene-induced renal toxicity.

Blocking the Wnt/ß-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting ß-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice.

Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. While the pathogenesis of silicosis is not clearly understood, the Wnt/ß-catenin signaling pathway is thought to play a major role in lung fibrosis. To explore the role of Wnt/ß-catenin pathway in silicosis, we blocked Wnt/ß-catenin pathway both in silica-treated MLE-12 cells (a mouse pulmonary epithelial cell line) and in a mouse silicosis model by using a lentiviral vector expressing a short hairpin RNA silencing ß-catenin (Lv-shß-catenin). In vitro, Lv-shß-catenin significantly decreased the expression of ß-catenin, MMP2 and MMP9, and secretion of TGF-ß1. In vivo, intratracheal treatment with Lv-shß-catenin significantly reduced expression of ß-catenin in the lung and levels of TGF-ß1 in bronchoalveolar lavage fluid, and notably attenuated pulmonary fibrosis as evidenced by hydroxyproline content and collagen I\III synthesis in silica-administered mice. These results indicate that blockade of the Wnt/ß-catenin pathway can prevent the development of silica-induced lung fibrosis. Thus Wnt/ß-catenin pathway may be a target in prevention and treatment of silicosis.

[Evaluation of measurement uncertainty of welding fume in welding workplace of a shipyard].

OBJECTIVE: To evaluate the measurement uncertainty of welding fume in the air of the welding workplace of a shipyard, and to provide quality assurance for measurement. METHODS: According to GBZ/T 192.1-2007 "Determination of dust in the air of workplace-Part 1: Total dust concentration" and JJF 1059-1999 "Evaluation and expression of measurement uncertainty", the uncertainty for determination of welding fume was evaluated and the measurement results were completely described. RESULTS: The concentration of welding fume was 3.3 mg/m(3), and the expanded uncertainty was 0.24 mg/m(3). The repeatability for determination of dust concentration introduced an uncertainty of 1.9%, the measurement using electronic balance introduced a standard uncertainty of 0.3%, and the measurement of sample quality introduced a standard uncertainty of 3.2%. CONCLUSION: During the determination of welding fume, the standard uncertainty introduced by the measurement of sample quality is the dominant uncertainty. In the process of sampling and measurement, quality control should be focused on the collection efficiency of dust, air humidity, sample volume, and measuring instruments.

Roles of oxidative damage and mitochondria-mediated apoptosis in ethylbenzene-induced hepatotoxic effects in rat.

The mechanisms underlying hepatoxic effects of ethylbenzene still remain unknown. We investigated the toxic effects of ethylbenzene on liver and explored the mechanism of mitochondria-mediated apoptosis pathway. Forty male Sprague-Dawley rats were used as an in vivo model with ethylbenzene inhalation of 0, 433.5 mg/m(3), 4335 mg/m(3) and 6500 mg/m(3) for 13 weeks. Levels of malondialdehyde, glutathione, glutathione peroxidase and superoxide dismutase were assayed. Meanwhile, the ultrastructure of hepatic tissues was observed and cell apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Furthermore, we investigated the expression levels of mRNA and protein of bax, bcl-2, cytochrome c, caspase-9 and caspase-3 in rat liver tissues. Compared with control group, the malondialdehyde levels were significantly elevated while glutathione levels and activities of glutathione peroxidase and superoxide dismutase were decreased, respectively. The mitochondria of liver appeared swollen with vacuolar structure and loss of cristae in 6500 mg/m(3) ethylbenzene-treated group, and ethylbenzene induced a significant increase in the percentage of apoptotic cells as compared to the control group. In addition, enhanced mRNA and protein expression levels of all measured genes were observed in ethylbenzene-treated groups except the decreased bcl-2 expression levels. Our results indicated that ethylbenzene may induce oxidative damage and apoptosis in rat liver. Mitochondrial-mediated pathway was involved in the apoptosis process.

[Effect of smoking on the microRNAs expression in pneumoconiosis patients].

OBJECTIVE: To investigate the effect of smoking on the microRNAs (miRNAs) expression in pneumoconiosis patients. METHODS: Real-time qPCR was used to measure the expression levels of miR-21, miR-200c, miR-16, miR-204, miR-206, miR-155, let-7g, miR-30b, and miR-192 in 36 non-smoking patients with pneumoconiosis and 38 smoking patients with pneumoconiosis, and the differences in expression levels between the two groups were evaluated by two-independent samples t-test. RESULTS: The expression of miR-192 in serum showed a significant difference between non-smoking and smoking pneumoconiosis patients (P < 0.05), and it decreased gradually in smoking patients with stage I and II pneumoconiosis. In the serum of all pneumoconiosis patients, the expression level of miR-16 was the highest, while the expression level of miR-204 was the lowest. CONCLUSION: Pneumoconiosis patients have differential expression of miRNAs in serum, and smoking has an effect on the miRNAs expression in pneumoconiosis patients.

Gynecologic pain related to occupational stress among female factory workers in Tianjin, China.

BACKGROUND: Dysmenorrhea, dyspareunia, and non-cyclic pelvic pain are health concerns for factory workers in China and may be increased by occupational stress. OBJECTIVES: To estimate the prevalence and demographic and occupational factors associated with three types of gynecologic pain among female factory workers in Tianjin. METHODS: The study included 651 female workers from three factories in Tianjin, China. Logistic regression models were estimated to determine associations between occupational stress and gynecologic pain. RESULTS: Occupational stress including high job strain, exhaustion, and stress related to working conditions was a risk factor for gynecologic pain. High job strain and poor job security were associated with an increased risk for dysmenorrhea. Compulsory overtime and exhaustion were associated with increased non-cyclic pelvic pain. Working overtime and exhaustion were associated with increased dyspareunia. CONCLUSIONS: As China's population of female factory workers grows, research on the reproductive health of this population is essential.

[Effect of toluene diisocyanate on lung function of workers].

OBJECTIVE: To investigate the effect of long-term exposure to toluene diisocyanate (TDI) on the lung function of TDI-exposed workers. METHODS: A factory was selected for this occupational epidemiological investigation. The workers who were exposed to TDI and had complete physical examination records in recent 3 years were the exposed group (n = 45), while the company's administrative staff, logistics staff, and other non-TDI-exposed workers who had complete physical examination records in recent 3 years were the control group (n = 47). The two groups were compared in terms of lung function indices. RESULTS: Compared with the control group, the 2009 exposure group had significantly lower forced expiratory volume in one second (FEV1.0), FEV1.0/forced vital capacity (FVC), and maximal expiratory flow at 25% of FVC (MEF25) (P < 0.05), the 2010 exposure group had significantly lower FEV1.0, FEV1.0/FVC,maximum voluntary ventilation (MVV), and maximal expiratory flow at 50% of FVC (MEF50) (P < 0.05), and the 2011 exposure group had significantly lower FEV1.0, FEV1.0/FVC, peak expiratory flow (PEF), MEF25, and MEF50 (P < 0.05). CONCLUSION: Long-term exposure to TDI can lead to certain impairment of lung function in workers, which may be reflected by decreased lung function indices such as vital capacity, FVC, FEV1.0, FEV1.0/FVC, PEF, and MVV.

[The inhibitory effect of latent transforming growth factor ß1 activation and silicosis by CD36 targeted RNA interference in silicosis model of rat].

OBJECTIVE: To investigate the inhibitory effects of CD36-targeting RNA interference on the latent transforming growth factor ß1 (L-TGF-ß1) activation and silicotic fibrosis in rat silicosis model. METHODS: Wistar rats were divided into four groups: saline control group (n=24), SiO2 model group (10 mg SiO2 per rat) (n=24), SiO2+Lv-shCD36 group (lentiviral vector expressing specific shRNA against CD36) (n=24), and SiO2+Lv-shCD36-NC group (non-silence control lentivirus) (n=24). At 7, 21, and 28 d after instillation, the rats were sacrificed. The activity of TGF-ß1 in bronchoalveolar lavage fluid (BALF) was measured by evaluating its inhibitory effect on the proliferation of mink lung epithelial cells. The pathological changes of lung tissue were observed by HE staining and van Gieson staining. The hydroxyproline content in the lungs was determined by alkaline lysis method. RESULTS: At 7 d after instillation, the expression of CD36 mRNA in alveolar macrophages was significantly lower in the SiO2+Lv-shCD36 group than in the saline control group, SiO2 model group, and SiO2+Lv-shCD36-NC group (P < 0.05); the quantity and percentage of active TGF-ß1 in BALF were significantly lower in the SiO2+Lv-shCD36 group than in the SiO2 model group and SiO2+Lv-shCD36-NC group (P < 0.05). At 28 d after instillation, there were cellular silicotic nodules in the lungs of rats in SiO2+Lv-shCD36 group and fibrotic cellular silicotic nodules in the lungs of rats in SiO2 model group and SiO2+Lv-shCD36-NC group. At 21 and 28 d after instillation, the hydroxyproline content was significantly lower in the SiO2+Lv-shCD36 group than in the SiO2 model group and SiO2+Lv-sh CD36-NC group (P < 0.05). CONCLUSION: CD36-targeting RNA interference has inhibitory effects on the L-TGF-ß1 activation and silicotic fibrosis in rat silicosis model.

[Pathological changes of major organs after rats inhaled methyl ethyl ketone peroxide aerosol].

OBJECTIVE: To investigate the pathological changes of major organs in rats that have inhaled methyl ethyl ketone peroxide (MEKP) aerosol and to provide clues to the oxidative damage mechanism of MEKP. METHODS: A total of 100 Sprague-Dawley rats (male-to-female ratio = 1:1) were randomly and equally divided into blank control group, solvent control group, and 50, 500, and 1000 mg/m(3) MEKP exposure groups to inhale clean air, solvent aerosol, or MEKP for 6 h per day, 5 d per week, for 13 weeks. A rat model of subchronic MEKP exposure was established. The clinical manifestations during exposure were recorded. The organ coefficients of the kidney, thymus, and testis were calculated. The histopathological changes of the lung, liver, and testis were observed by HE staining. RESULTS: The male rats in 1000 mg/m(3) MEKP exposure group had significantly lower organ coefficients of the kidney and testis than those in blank control group, solvent control group, and 50 and 500 mg/m(3) MEKP exposure groups (P < 0.05). The rats in 1000 mg/m(3) MEKP exposure group had a significantly lower organ coefficient of the thymus than those in blank control group and solvent control group (P < 0.05). Some rats in 500 and 1000 mg/m3 MEKP exposure groups had significant damage to the lung, liver, and testis, which demonstrated a worsening trend as the dose increased. Pulmonary hyperinflation, hyperemia, bleeding, interstitial pneumonia, and even lung abscess were seen in the damaged lung. Nuclear enrichment, hepatocyte steatosis, and mild cellular edema in the portal area were seen in the damaged liver. Variable degeneration, necrosis, and dysplasia of spermatogenic cells and significant decrease in sperms in spermatogenic cells were seen in the damaged testis. The female rats in blank control group, solvent control group, and 50, 500, and 1000 mg/m(3) MEKP exposure groups showed no pathological changes in the ovary. CONCLUSION: Inhalation of MEKP aerosol can cause oxidative damage to the liver, lung, kidney, thymus, and testis in rats, particularly to the testis in male rats.