Low-dose hexavalent chromium induces mitophagy in rat liver via the AMPK-related PINK1/Parkin signaling pathway.

Hexavalent chromium (Cr(VI)) is a hazardous metallic compound commonly used in industrial processes. The liver, responsible for metabolism and detoxification, is the main target organ of Cr(VI). Toxicity experiments were performed to investigate the impacts of low-dose exposure to Cr(VI) on rat livers. It was revealed that exposure of 0.05 mg/kg potassium dichromate (K2Cr2O7) and 0.25 mg/kg K2Cr2O7 notably increased malondialdehyde (MDA) levels and the expressions of P-AMPK, P-ULK, PINK1, P-Parkin, and LC3II/LC3I, and significantly reduced SOD activity and P-mTOR and P62 expression levels in liver. Electron microscopy showed that CR(VI) exposure significantly increased mitophagy and the destruction of mitochondrial structure. This study simulates the respiratory exposure mode of CR(VI) workers through intratracheal instillation of CR(VI) in rats. It confirms that autophagy in hepatocytes is induced by low concentrations of CR(VI) and suggest that the liver damage caused by CR(VI) may be associated with the AMPK-related PINK/Parkin signaling pathway.

Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1α mediated oxidative stress.

Apigenin (API) is a natural flavonoid compound with antioxidant, anti fibrotic, anti-inflammatory and other effects, but there is limited research on the effect of API on liver fibrosis. This study aims to explore the effect and potential mechanism of API on liver fibrosis induced by CCl4 in mice. The results indicate that API reduces oxidative stress levels, inhibits hepatic stellate cell (HSC) activation, and exerts anti liver fibrosis effects by regulating the PKM2-HIF-1α pathway. We observed that API alleviated liver tissue pathological damage and collagen deposition in CCl4 induced mouse liver fibrosis model, promoting the recovery of liver function in mice with liver fibrosis. In addition, the API inhibits the transition of Pyruvate kinase isozyme type M2 (PKM2) from dimer to tetramer formation by regulating the EGFR-MEK1/2-ERK1/2 pathway, thereby preventing dimer from entering the nucleus and blocking PKM2-HIF-1α access. This change leads to a decrease in malondialdehyde (MDA) and Catalase (CAT) levels and an increase in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels, as well as total antioxidant capacity (T-AOC) in the liver of liver fibrosis mice. At the same time, API downregulated the expression of α-smooth muscle actin (α-SMA), Vimentin and Desmin in the liver tissue of mice with liver fibrosis, inhibited the activation of HSC, and reduced collagen deposition. These results indicate that API can inhibit HSC activation and alleviate CCl4 induced liver fibrosis by inhibiting the PKM2-HIF-1α pathway and reducing oxidative stress, laying an important foundation for the development and clinical application of API as a novel drug for treating liver fibrosis.

Immune Regulation Patterns in Response to Environmental Pollutant Chromate Exposure-Related Genetic Damage: A Cross-Sectional Study Applying Machine Learning Methods.

Exposure to hexavalent chromium damages genetic materials like DNA and chromosomes, further elevating cancer risk, yet research rarely focuses on related immunological mechanisms, which play an important role in the occurrence and development of cancer. We investigated the association between blood chromium (Cr) levels and genetic damage biomarkers as well as the immune regulatory mechanism involved, such as costimulatory molecules, in 120 workers exposed to chromates. Higher blood Cr levels were linearly correlated with higher genetic damage, reflected by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and blood micronucleus frequency (MNF). Exploratory factor analysis revealed that both positive and negative immune regulation patterns were positively associated with blood Cr. Specifically, higher levels of programmed cell death protein 1 (PD-1; mediated proportion: 4.12%), programmed cell death ligand 1 (PD-L1; 5.22%), lymphocyte activation gene 3 (LAG-3; 2.11%), and their constitutive positive immune regulation pattern (5.86%) indirectly positively influenced the relationship between blood Cr and urinary 8-OHdG. NOD-like receptor family pyrin domain containing 3 (NLRP3) positively affected the association between blood Cr levels and inflammatory immunity. This study, using machine learning, investigated immune regulation and its potential role in chromate-induced genetic damage, providing insights into complex relationships and emphasizing the need for further research.

Cellular senescence mediates hexavalent chromium-associated lung function decline: Insights from a structural equation Model.

There is sufficient evidence suggesting that exposure to hexavalent chromium [Cr(VI)] can cause a decline in lung function and the onset of lung diseases. However, no studies have yet explored the underlying mechanisms of these effects from various perspectives such as systemic inflammation, oxidative stress, and cellular senescence, simultaneously. This cross-sectional study was conducted among 304 workers engaged in chromate production and processing in China. Urine was used for detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α), while RNA and DNA extraction from peripheral blood cells was used for detection of mRNA, telomere length, and ribosomal DNA copy numbers (rDNA CNs). A 2.7-fold elevation in blood chromate (Cr) corresponded to a 7.86% (95% CI: 2.57%, 13.42%) rise in urinary 8-OHdG and a 4.14% (0.02%, 8.42%) increase in urinary 8-iso-PGF2α, indicating that exposure to chromates can cause oxidative stress. Furthermore, strong correlations emerged between blood Cr concentration and mRNA levels of P16, P21, TP53, and P15 in the cellular senescence pathway. Simultaneously, a 2.7-fold elevation in blood Cr associated with a -5.47% (-8.72%, -2.1%) change in telomere length, while rDNA CNs (5S, 5.8S, 18S, and 28S) changed by -3.91% (-7.99%, 0.34%), -9.4% (-15.73%, -2.6%), -8.06% (-14.01%, -1.69%), and -5.86% (-10.67%, -0.78%), respectively. Structural equation model highlighted that cellular senescence exerted significant indirect effects on Cr(VI)-associated lung function decline, with a mediation proportion of 23.3%. This study provided data supporting for 8-iso-PGF2α, telomere length, and rDNA CNs as novel biomarkers of chromate exposure, emphasizing the significant role of cellular senescence in the mechanism underlying chromate-induced lung function decline.

Variations in the Cadherin 23 Gene Associated With Noise-Induced Hearing Loss.

Background: The relationship between CDH23 gene variants and NIHL is unclear. This study investigates the association between cadherin 23 (CDH23) gene variants and noise-induced hearing loss (NIHL). Methods: This is a case-control study. Workers who were exposed to noise from a steel factory in North China were recruited and divided into two groups: the case group (both ears' high-frequency threshold average [BHFTA] ≥40dB) and the control group (BHFTA ≤25 dB). This study used the generalised multifactor dimensionality reduction method to analyse the association among 18 single-nucleotide polymorphisms (SNPs) in CDH23 and NIHL. Logistic regression was performed to investigate the main effects of SNPs and the interactions between cumulative noise exposure (CNE) and SNPs. Furthermore, CNE was adjusted for age, gender, smoking, drinking, physical exercise and hypertension. Results: This study recruited 1,117 participants. The results showed that for rs11592462, participants who carried the GG genotype showed an association with NIHL greater than that of those who carried the CC genotype. Accordingly, genetic variation in the CDH23 gene could play an essential role in determining individual susceptibility to NIHL. Conclusion: Genetic variations in the CDH23 gene may play an important role in determining individual susceptibility to NIHL. These results provide new insight into the pathogenesis and early prevention of NIHL.

Relationships between blood chromium exposure and liver injury: Exploring the mediating role of systemic inflammation in a chromate-exposed population.

Hexavalent chromium and its compounds are prevalent pollutants, especially in the work environment, pose a significant risk for multisystem toxicity and cancers. While it is known that chromium accumulation in the liver can cause damage, the dose-response relationship between blood chromium (Cr) and liver injury, as well as the possible potential toxic mechanisms involved, remains poorly understood. To address this, we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), and to evaluate the mediating effects of systemic inflammation. Platelet (PLT) and the platelet-to-lymphocyte ratio (PLR) were utilized as biomarkers of systemic inflammation. In the linear mixed-effects analyses, each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82% (0.11%, 1.53%) in TBIL, 1.67% (0.06%, 3.28%) in DBIL, 0.73% (0.04%, 1.43%) in ALT and 2.08% (0.29%, 3.87%) in AST, respectively. Furthermore, PLT mediated 10.04%, 11.35%, and 10.77% increases in TBIL, DBIL, and ALT levels induced by chromate, respectively. In addition, PLR mediated 8.26% and 15.58% of the association between blood Cr and TBIL or ALT. These findings shed light on the mechanisms underlying blood Cr-induced liver injury, which is partly due to worsening systemic inflammation.

Low-Dose Hexavalent Chromium Exposure Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Rat Liver.

This study investigated the toxic effects of low-dose hexavalent chromium (Cr(VI)) on rat liver. Male specific pathogen-free (SPF) Sprague-Dawley (SD) rats (4-5 weeks of age) were randomly divided into groups: saline, 0.05 mg/kg Cr(VI), and 0.25 mg/kg Cr(VI). The rats were subjected to intratracheal instillation of K2Cr2O7 suspensions or saline once weekly, for a total of five times. The results showed that the accumulation of Cr(VI) in the blood of the 0.25 mg/kg K2Cr2O7 group was significantly higher than that in the saline group. Transmission electron microscopy (TEM) showed that exposure to hexavalent chromium caused endoplasmic reticulum (ER) oedema and a disordered arrangement. The levels of endoplasmic reticulum stress (ERS)-related proteins (ATF6, P-PERK, P-IRE1, Grp78, and CHOP) in the 0.25 mg/kg K2Cr2O7 group were significantly higher than those in the saline group. The expression of apoptosis-inhibitory protein Bcl-2 was significantly lower in the 0.25 mg/kg K2Cr2O7 group than that in the saline group, and the expression of apoptosis protein Bax was significantly higher in the 0.25 mg/kg K2Cr2O7 group than that in the saline group, indicating that Cr(VI) increased apoptosis. These findings revealed that Cr(VI) may be involved in rat liver injury by initiating ERS-mediated apoptosis. The expression of ATF6, P-PERK, P-IRE1, and Bax in the 0.05 mg/kg K2Cr2O7 group was not significantly different from that in the saline group, and the different effects produced by the two different dose groups provide a possible experimental basis for further study of occupational exposure limits.

Hexavalent chromium caused DNA damage repair and apoptosis via the PI3K/AKT/FOXO1 pathway triggered by oxidative stress in the lung of rat.

Hexavalent chromium [Cr(VI)] is an occupational carcinogen that accumulates in the lungs and causes lung injury and even lung cancer. 36 SD male rats received inhalable intratracheal instillation of Cr(VI) (0.05, 0.25 mg Cr/kg) or the same volume (3 ml/kg) of normal saline weekly for 28 days (total 5 times). After 28 days of exposure, half of the rats in each group were sacrificed for investigation, and the rest stopped exposure and began to be self-repaired for two weeks. Histopathology analyses revealed that Cr(VI) induced slight dilatation and hemorrhage of perialveolar capillaries, pulmonary bronchodilation, and congestion with peripheral flaky-like necrosis accompanied by inflammatory cell infiltration, especially the 0.25 mg Cr/kg group. Cr(VI) exposure caused the increase of blood Cr, urinary Cr, MDA, urinary 8-hydroxy-2' -deoxyguanosine (8-OHdG), and the decrease of GSH and MDA, while two-week repair only reduced urinary Cr. Exposure to Cr(VI) significantly upregulated FOXO1 and downregulated p-AKT and p-FOXO1 for two weeks. PI3K in the 0.25 mg Cr/kg group was inhibited after two weeks of repair. Cr(VI) exposure mainly promoted GADD45a and CHK2 in the exposure group, promoted Bim, Bax/Bcl-2, and suppressed Bcl-2 and Bcl-xL in the repair group. These results demonstrate that Cr(VI) may induce DNA damage repair and apoptosis in the lung by activating the PI3K/AKT/FOXO1 pathway. Two-week repair may alleviate oxidative stress and DNA damage induced by Cr(VI) exposure but couldn't eliminate its effects. This study provides a new perspective for exploring the Cr(VI) induced lung cancer mechanism.

Dysregulations of metabolites and gut microbes and their associations in rats with noise induced hearing loss.

Background: Noise exposure could lead to hearing loss and disorders of various organs. Recent studies have reported the close relations of environmental noise exposure to the metabolomics dysregulations and gut microbiota disturbance in the exposers. However, the associations between gut microbial homeostasis and the body metabolism during noise-induced hearing loss (NIHL) were unclear. To get a full understanding of their synergy in noise-associated diseases, it is essential to uncover their impacts and associations under exposure conditions. Methods: With ten male rats with background noise exposure (≤ 40 dB) as controls (Ctr group), 20 age- and weight-matched male rats were exposed to 95 dB Sound pressure level (SPL) (LN group, n = 10) or 105 dB SPL noise (HN group, n = 10) for 30 days with 4 h/d. The auditory brainstem response (ABR) of the rats and their serum biochemical parameters were detected to investigate their hearing status and the potential effects of noise exposure on other organs. Metabolomics (UPLC/Q-TOF-MS) and microbiome (16S rDNA gene sequencing) analyses were performed on samples from the rats. Multivariate analyses and functional enrichments were applied to identify the dysregulated metabolites and gut microbes as well as their associated pathways. Pearson correlation analysis was performed to investigate the associations of the dysregulations of microbiota and the metabolites. Results: NIHL rat models were constructed. Many biochemical parameters were altered by noise exposure. The gut microbiota constitution and serum metabolic profiles of the noise-exposed rats were also dysregulated. Through metabolomics analysis, 34 and 36 differential metabolites as well as their associated pathways were identified in LN and HN groups, respectively. Comparing with the control rats, six and 14 florae were shown to be significantly dysregulated in the LN group and HN group, respectively. Further association analysis showed significant correlations between differential metabolites and differential microbiota. Conclusion: There were cochlea injuries and abnormalities of biochemical parameters in the rats with NIHL. Noise exposure could also disrupt the metabolic profiles and the homeostatic balance of gut microbes of the host as well as their correlations. The dysregulated metabolites and microbiota might provide new clues for prevention of noise-related disorders.

Relationship between systemic inflammation and lung injury induced by chromate exposure: A cross-sectional study in workers.

Hexavalent chromium [Cr(VI)] compounds, known as "Group I Human Carcinogen" and "Category I Respiratory Sensitizer", posed great challenges to the respiratory system. A cross-sectional study was undertaken among chromate workers. Serum club cell protein 16 (CC16) and soluble urokinase-type plasminogen activator receptor (suPAR) were measured using ELISA. Thirteen macrophage-related mediators were tested using cytometric bead array. After controlling for sex, age, smoking status, drinking status and BMI, each increase of one-unit of Ln-transformed blood Cr was related to the increase of IL-1beta [Beta (95% CI), 7.22(1.14, 13.29)%, P = 0.021], IL-23 [8.5(1.15, 15.85)%, P = 0.021], IFN-gamma [3.14(0.15, 6.13)%, P = 0.040], and suPAR [9.31(2.5, 16.12) %, P = 0.008], as well as the increase of CC16 by 3.88(0.42, 7.34) % (P = 0.029). Moreover, these inflammatory mediators played an mediation role in the rise of CC16 caused by Cr(VI). The exposure-response curve analysis revealed a substantial nonlinear association of IFN-gamma and suPAR with CC16, thus the mediation effect of INF-gamma and suPAR required cautious interpretation. The positive connection between macrophage-related mediators was stronger in the high exposure group than in the low exposure group, suggesting that high concentration of chromate might promote a complex interplay within the immune system.

Two-week repair alleviates hexavalent chromium-induced hepatotoxicity, hepatic metabolic and gut microbial changes: A dynamic inhalation exposure model in male mice.

Hexavalent chromium [Cr(VI)] has been identified as a "Group I human carcinogen" with multisystem and multiorgan toxicity. A dynamic inhalation exposure model in male mice, coupled with the hepatic metabolome and gut microbiome, was used to explore hepatotoxicity, and hepatic metabolic and gut microbial changes under the exposure scenarios in the workspace and general environment. The present study set up an exposure group (EXP) that inhaled 150 µg Cr/m3 for 13 weeks, a control group (CONT) that inhaled purified air, as well as a two-week repair group (REXP) after 13 weeks of exposure and the corresponding control group (RCONT). Cr(VI) induced elevation of hepatic Cr accumulation, the ratio of ALT and AST, and folate in serum. Inflammatory infiltration in the liver and abnormal mitochondria in hepatocytes were also induced by Cr(VI). Glutathione, ascorbate, folic acid, pantetheine, 3'-dephospho-CoA and citraconic acid were the key metabolites affected by Cr(VI) that were associated with significant pathways such as pantothenate and CoA biosynthesis, hypoxia-inducible factor-1 signaling pathway, antifolate resistance, alpha-linolenic acid metabolism and one carbon pool by folate. g_Allobaculum was identified as a sensitive biomarker of Cr(VI) exposure because g_Allobaculum decreased under Cr(VI) exposure but increased after repair. The gut microbiota might be involved in the compensation of hepatotoxicity by increasing short-chain fatty acid-producing bacteria, including g_Lachnospiraceae_NK4A136_group, g_Blautia, and f_Muribaculaceae. After the two-week repair, the differential metabolites between the exposed and control groups were reduced from 73 to 29, and the KEGG enrichment pathways and differential microbiota also decreased. The mechanism for repair was associated with reversion of lipid peroxidation and energy metabolism, as well as activation of protective metabolic pathways, such as the AMPK signaling pathway, longevity regulating pathway, and oxidative phosphorylation. These findings might have theoretical and practical implications for better health risk assessment and management.

Plasma metabolomics analyses highlight the multifaceted effects of noise exposure and the diagnostic power of dysregulated metabolites for noise-induced hearing loss in steel workers.

Noise exposure can lead to various kinds of disorders. Noise-induced hearing loss (NIHL) is one of the leading disorders confusing the noise-exposed workers. It is essential to identify NIHL markers for its early diagnosis and new therapeutic targets for its treatment. In this study, a total of 90 plasma samples from 60 noise-exposed steel factory male workers (the noise group) with (NIHL group, n = 30) and without NIHL (non-NIHL group, n = 30) and 30 male controls without noise exposure (control group) were collected. Untargeted human plasma metabolomic profiles were determined with HPLC-MS/MS. The levels of the metabolites in the samples were normalized to total peak intensity, and the processed data were subjected to multivariate data analysis. The Wilcoxon test and orthogonal partial least square-discriminant analysis (OPLS-DA) were performed. With the threshold of p < 0.05 and the variable importance of projection (VIP) value >1, 469 differential plasma metabolites associated with noise exposure (DMs-NE) were identified, and their associated 58 KEGG pathways were indicated. In total, 33 differential metabolites associated with NIHL (DMs-NIHL) and their associated 12 KEGG pathways were identified. There were six common pathways associated with both noise exposure and NIHL. Through multiple comparisons, seven metabolites were shown to be dysregulated in the NIHL group compared with the other two groups. Through LASSO regression analysis, two risk models were constructed for NIHL status predication which could discriminate NIHL from non-NIHL workers with the area under the curve (AUC) values of 0.840 and 0.872, respectively, indicating their efficiency in NIHL diagnosis. To validate the results of the metabolomics, cochlear gene expression comparisons between susceptible and resistant mice in the GSE8342 dataset from Gene Expression Omnibus (GEO) were performed. The immune response and cell death-related processes were highlighted for their close relations with noise exposure, indicating their critical roles in noise-induced disorders. We concluded that there was a significant difference between the metabolite's profiles between NIHL cases and non-NIHL individuals. Noise exposure could lead to dysregulations of a variety of biological pathways, especially immune response and cell death-related processes. Our results might provide new clues for noise exposure studies and NIHL diagnosis.

Blood chromium exposure, immune inflammation and genetic damage: Exploring associations and mediation effects in chromate exposed population.

Both genetic damage and inappropriate immune function are relevant to cancer of hexavalent chromium [Cr(VI)]. However, its associations with immune response and genetic damage development are poorly understood. To explore their associations and mediating effects, 1249 participants were included from the Occupational Chromate Exposure Dynamic Cohort, and their blood Cr concentrations were measured as internal exposure. A set of biomarkers including urinary 8-hydroxy-2' - deoxyguanosine (8-OHdG), micronucleus frequency (MNF) and mitochondrial DNA copy number (mtCN) was developed to evaluate the landscape of genetic damage of Cr(VI). Serum C-reactive protein (CRP) and first component of complement q (C1q) were measured to reflect immune inflammation. Multivariate linear regression and mediation analyses were applied to assess the potential associations and mediation effects. It was found that blood Cr level showed significant dose-dependent relationships with increasing of MNF and urinary 8-OHdG, while negative association with CRP and C1q. Furthermore, a 1-unit increase in CRP was associated with decreases of - 0.765 to - 0.254 in MNF, - 0.400 to - 0.051 in urinary 8-OHdG. 4.97% of the association between blood Cr level and the increased MNF was mediated by CRP. 11.58% of the relationship between concentration of blood Cr and urinary 8-OHdG was mediated by C1q. These findings suggested that Cr(VI) exposures might prompt genetic damage, possibly partial via worsening immune inflammation.

Lung function assessment and its association with blood chromium in a chromate exposed population.

Hexavalent chromium [Cr(VI)] and its compounds have been associated with various respiratory diseases, while few studies have attempted to determine its adverse effect on lung function. To explore the potential early indicators of health surveillance for respiratory diseases induced by chromate exposure, a longitudinal cohort study including 515 workers with 918 measurements across 2010-2017 was conducted to investigate the impact of individual internal exposure on lung function. Inductively coupled plasma mass spectrometry (ICP-MS) and spirometry were used to measure whole blood chromium (blood Cr) and lung function respectively. In the linear mixed-effects analysis, each 1- unit increase in Ln- transformed blood Cr was significantly associated with estimated effect percentage decreases of 1.80 (0.35, 3.15) % in FEV1, 0.77 (0.10, 1.43) % in FEV1/FVC, 2.78 (0.55, 4.98) % in PEF, and 2.73 (0.59, 4.71) % in FEF25-75% after adjusting for related covariates. Exposure- response curve depicted the reduction of lung function with blood Cr increase, and the reference value of blood Cr was proposed as 6 µg/L considering the lung function as health outcome. Based on the repeated-measure analysis, compared with the low frequency group, subjects with high frequency of high exposure across 2010-2017 had an additional reduction of 5.65 (0, 11.3) % in FVC. Subjects with medium frequency showed more obvious declines of 9.48 (4.16, 14.87) % in FVC, 8.63 (3.49, 13.97) % in FEV1, 12.94 (3.34, 22.53) % in PEF and 10.97 (3.63, 18.30) % in MVV. These findings suggested that short- term high exposure to Cr associated with obstructive ventilatory impairment, and long- term exposure further led to restrictive ventilatory impairment.

Blood leukocyte count as a systemic inflammatory biomarker associated with a more rapid spirometric decline in a large cohort of iron and steel industry workers.

OBJECTIVE: Iron and steel industry workers are exposed to high levels of inhalable dust particles that contain various elements, including metals, and cause occupational lung diseases. We aim to assess the relationship between occupational dust exposure, systemic inflammation, and spirometric decline in a cohort of Chinese iron and steel workers. METHODS: We studied 7513 workers who participated in a Health Surveillance program at Wugang Institute for Occupational Health between 2008 and 2017. Time-weighted exposure intensity (TWEI) of dust was quantified based on self-reported dust exposure history, the experience of occupational hygienists, and historical data of dust exposure for workers with certain job titles. A linear mixed-effects model was used for association analyses. RESULTS: The average annual change of lung function was - 50.78 ml/year in forced expiratory volume in 1 s (FEV1) and - 34.36 ml/year in forced vital capacity (FVC) in males, and - 39.06 ml/year in FEV1 and - 26.66 ml/year in FVC in females. Higher TWEI prior to baseline was associated with lower longitudinal measurements of FEV1 and FVC but not with their decline rates. Higher WBC and its differential at baseline were associated with lower longitudinal measurements and a more rapid decline of FEV1 and FVC in a dose-dependent monotonically increasing manner. Moreover, the increase of WBC and its differential post-baseline was also associated with a more rapid decline of FEV1 and FVC. CONCLUSIONS: Our findings support the important role of systemic inflammation in affecting the temporal change of lung function in iron and steel industry workers.

Analysis of serum metabolome of workers occupationally exposed to hexavalent chromium: A preliminary study.

Hexavalent chromium (Cr(VI)) compound is considered as a common environmental and occupational pollutant due to widespread application in industry and agriculture. Cr(VI) as a carcinogen poses a serious threat to human health and the underlying mechanisms need further investigation. Previous studies had demonstrated the characteristic expression profiling after Cr(VI) treatment in vitro and in vivo at the levels of gene and protein. The comprehensive metabolic signatures were also conducive to discover potential biomarkers for effects assessment of Cr(VI) toxicity. In the current study, Ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) non-targeted metabolomics was applied to analyze serum metabolic changes in 77 chromate exposure workers and 62 controls. Thirteen metabolites were found significantly decreased and 41 metabolites were increased, which were involved in arginine and proline metabolism, and glycerophospholipid metabolism by bioinformatic analysis. Furthermore, there were significant negative correlations between blood Cr level and Arginine, PC(18:2/24:4) and PC(14:0/16:0), subgroup analyses indicated that these correlations were observed in male-only subgroups, and were not found among chromate workers and controls separately. Diet could be a potential confounder which was not controlled rigorously in this study. These findings provided preliminary clues to investigate the underlying mechanisms of Cr(VI)-induced toxicity and were required to be further verified in future researches.

Chronic exposure to diesel exhaust may cause small airway wall thickening without lumen narrowing: a quantitative computerized tomography study in Chinese diesel engine testers.

BACKGROUND: Diesel exhaust (DE) is a major source of ultrafine particulate matters (PM) in ambient air and contaminates many occupational settings. Airway remodeling assessed using computerized tomography (CT) correlates well with spirometry in patients with obstructive lung diseases. Structural changes of small airways caused by chronic DE exposure is unknown. Wall and lumen areas of 6th and 9th generations of four candidate airways were quantified using end-inhalation CT scans in 78 diesel engine testers (DET) and 76 non-DETs. Carbon content in airway macrophage (CCAM) in sputum was quantified to assess the dose-response relationship. RESULTS: Environmental monitoring and CCAM showed a much higher PM exposure in DETs, which was associated with higher wall area and wall area percent for 6th generation of airways. However, no reduction in lumen area was identified. No study subjects met spirometry diagnosis of airway obstruction. This suggested that small airway wall thickening without lumen narrowing may be an early feature of airway remodeling in DETs. The effect of DE exposure status on wall area percent did not differ by lobes or smoking status. Although the trend test was of borderline significance between categorized CCAM and wall area percent, subjects in the highest CCAM category has a 14% increase in wall area percent for the 6th generation of airways compared to subjects in the lowest category. The impact of DE exposure on FEV1 can be partially explained by the wall area percent with mediation effect size equal to 20%, Pperm = 0.028). CONCLUSIONS: Small airway wall thickening without lumen narrowing may be an early image feature detected by CT and underlie the pathology of lung injury in DETs. The pattern of changes in small airway dimensions, i.e., thicker airway wall without lumen narrowing caused by occupational DE exposure was different to that (i.e., thicker airway wall with lumen narrowing) seen in our previous study of workers exposed to nano-scale carbon black aerosol, suggesting constituents other than carbon cores may contribute to such differences. Our study provides some imaging indications of the understanding of the pulmonary toxicity of combustion derived airborne particulate matters in humans.

Circulating lead modifies hexavalent chromium-induced genetic damage in a chromate-exposed population: An epidemiological study.

Chromium (Cr) can coexist with other heavy metals in the blood of chronically chromate-exposed individuals. However, few studies have explored the health impacts of other hazardous metals after exposure to hexavalent chromium [Cr(VI)]. This study aimed to assess the modification effects of blood lead (Pb) on the genetic damage induced by Cr(VI). During 2010-2019, 1000 blood samples were collected from 455 workers exposed to chromate and 545 workers not exposed to chromate from the same factory with similar labor intensity. The levels of Cr and Pb were measured in whole blood samples. Micronucleus frequency (MNF) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured to reflect different types of genetic damage. Multivariate linear regression analyses were performed to evaluate the associations between hazardous metals and the modification effects of Pb on genetic damage. The geometric mean levels of Cr and Pb in the exposure group were significantly higher than those in the control group [Cr: 6.42 (6.08- 6.79) vs. 1.29 (1.22- 1.36) µg/L; Pb: 38.82 (37.22- 40.50) vs. 34.47 (33.15- 35.85) µg/L]. The geometric means of urinary 8-OHdG and MNF in exposure group were 4.00 (3.64- 4.40) µg/g and 5.40 (4.89- 5.97) ‰, respectively, significantly higher than the 3.20 (2.94- 3.48) µg/g and 4.57 (4.15- 5.03) ‰, respectively, in control group. log2Cr was independently and positively associated with urinary 8-OHdG (ß-adjusted = 0.143, 95% CI: 0.082- 0.204) and MNF (ß-adjusted = 0.303, 95%CI: 0.020- 0.587). With the change in circulating Pb levels, the types of genetic damage induced by Cr(VI) were different. At low levels of circulating Pb (<30.80 µg/L), chromate mainly caused changes in 8-OHdG, while at high circulating Pb levels (≥44.88 µg/L), chromate induced alterations in MNF. The findings suggested that chromate exposure could cause multiple types of genetic damage, and circulating Pb might modify the association between circulating Cr and the form of genetic damage.

[Association between single nucleotides polymorphism of catalase gene and susceptibility to noise-induced hearing loss in occupational population].

OBJECTIVE: To investigate the relationship between single nucleotides polymorphism of catalase(CAT) gene and susceptibility to noise-induced hearing loss(NIHL) in occupational noise exposed population. METHODS: A case-control study of 1∶1 was conducted to select 286 workers with binaural high frequency average hearing threshold ≥40 dB(HL), from 2006 to 2015 in a cohort study of occupational noise exposure workers in Henan Province. According to the type of work, the age difference was not more than 5 years and the length of exposure to noise was not more than 2 years. The polymorphism of 8 single nucleotides in CAT gene was detected by medium SNPscanTM, and the relationship between 8 single nucleotides polymorphism of CAT gene and NIHL susceptibility was analyzed by multivariate conditional logistic regression. RESULTS: Under the dominant model of rs208679 locus of CAT gene [(GA GG)/AA], the risk of NIHL in individuals carrying GA or GG genotype was 1. 431 times higher than that in individuals carrying AA genotype(95%CI 1. 020-2. 009), and P=0. 038. CONCLUSION: G, a mutant at rs208679 site of CAT gene, may be one of the risk factors for NIHL susceptibility.

Small Airway Wall Thickening Assessed by Computerized Tomography Is Associated With Low Lung Function in Chinese Carbon Black Packers.

Nanoscale carbon black as virtually pure elemental carbon can deposit deep in the lungs and cause pulmonary injury. Airway remodeling assessed using computed tomography (CT) correlates well with spirometry in patients with obstructive lung diseases. Structural airway changes caused by carbon black exposure remain unknown. Wall and lumen areas of sixth and ninth generations of airways in 4 lobes were quantified using end-inhalation CT scans in 58 current carbon black packers (CBPs) and 95 non-CBPs. Carbon content in airway macrophage (CCAM) in sputum was quantified to assess the dose-response. Environmental monitoring and CCAM showed a much higher level of elemental carbon exposure in CBPs, which was associated with higher wall area and lower lumen area with no change in total airway area for either airway generation. This suggested small airway wall thickening is a major feature of airway remodeling in CBPs. When compared with wall or lumen areas, wall area percent (WA%) was not affected by subject characteristics or lobar location and had greater measurement reproducibility. The effect of carbon black exposure status on WA% did not differ by lobes. CCAM was associated with WA% in a dose-dependent manner. CBPs had lower FEV1 (forced expiratory volume in 1 s) than non-CBPs and mediation analysis identified that a large portion (41-72%) of the FEV1 reduction associated with carbon black exposure could be explained by WA%. Small airway wall thickening as a major imaging change detected by CT may underlie the pathology of lung function impairment caused by carbon black exposure.