Influence of chitotriosidase gene polymorphisms on oxidative stress and susceptibility to Aspergillus infection among exposed workers.

Chitotriosidase (CHIT1) is involved in the innate defense against chitin-containing pathogens. In the present study, we sought to investigate the role of CHIT1 gene polymorphisms on susceptibility to Aspergillus infection in addition to oxidative stress caused by infection. CHIT1 gene polymorphisms were identified in 60 Aspergillus-positive workers by REFLP. We also measured concentrations of the CHIT1 enzyme, total antioxidant capacity (TAC), and malondialdehyde (MDA). The majority of workers were wild-type (AA) (66.5%), followed by heterozygous (AB) (28.5%), and homozygous mutants (BB) (5%). The mean concentrations of specific IgE for all Aspergillus species were affected by change in CHIT1 genotypes. Our findings indicate that decreased CHIT1 activity in homozygous mutant CHIT1 allele is associated with a subsequent decrease in TAC levels, resulting in an increased risk of fungal infection and accumulation of oxidant MDA. Thus, CHIT1 enzyme activity plays a critical role in the susceptibility of WWTP workers to fungal infections.

Nephrotoxic effect of heavy metals and the role of DNA repair gene among secondary aluminum smelter workers.

This study aims to estimate the association between some heavy metals in suspended particulate matter (SPM) and kidney damage among workers at different departments in a secondary aluminum production plant. It also investigates the association between Xeroderma Pigmentosum complementation group D (XPD) gene polymorphisms and worker's susceptibility to kidney dysfunction. It was conducted on 30 workers from the administrative departments and 147 workers from different departments in the production line. Estimation of some heavy metals (Al, Co, Ni, Cu, Pb, and Cd) in suspended particulate matter (SPM) is done. Also, urinary levels of those metals were measured for all workers. Kidney injury molecule 1 (KIM-1), clusterin levels, and XPD protein level were estimated. Genotyping of XPD gene polymorphisms was performed. The measured annual average concentrations of the estimated heavy metals were lower than the permissible limits. Gravity area had the maximum concentration of metals with a higher Al average daily dose and hazardous index > 1. Kidney injury biomarkers (clusterin and KIM-1) were increased significantly (p < 0.05) while XPD protein showed the lowest levels among workers at the gravity and cold rolling areas. XPD Asn/Asp genotype was more dominant among those workers (85.7%). Conclusion: aluminum workers are at risk of kidney disorders due to heavy metal exposure. The individual's susceptibility to the diseases is related to the DNA repair efficiency mechanisms. The defect in XPD protein represents a good indicator of susceptibility to the disease. KIM-1 and clusterin estimation is a predictor biomarker for early-staged kidney diseases.

Lung cancer risk in workers occupationally exposed to polycyclic aromatic hydrocarbons with emphasis on the role of DNA repair gene.

OBJECTIVE: Workers in secondary aluminum production plants are occupationally exposed to polycyclic aromatic hydrocarbons (PAHs). We aimed to monitor the concentrations of PAHs in air and in serum of workers at two secondary aluminum production plants. We also investigated the potential risk of lung cancer development among PAHs exposed workers with emphasis on the role of A1AT mutation and APEX1 gene polymorphisms. METHODS: This study included 177 workers from administrative departments and production lines. Blood samples were obtained for estimation of benzo(a)pyrene diol epoxide albumin adduct (BPDE-Alb adduct), anti-Cyclin-B1 marker (CCNB1) and squamous cell carcinoma antigen (SCCAg). Genes' polymorphism for human apurinic/apyrimidinic endonuclease (APEX1) and alpha-1-anti-trypsin (A1AT) gene mutation were detected. RESULTS: There was a significant increase in the level of BPDE-Alb adduct among exposed workers in comparison to non-exposed group. Moreover, 41.67% of exposed workers in El Tebbin had BPDE-Alb adduct level ≥ 15 ng/ml versus 29.6% of workers in Helwan factory. There was a significant increase in tumor markers (SCCAg and CCNB1) among workers whose BPDE-Alb adduct ≥ 15 ng/ml. There was a significant increase in the level of BPDE-Alb adducts in exposed workers carrying homozygous APEX1 genotype Glu/Glu. Furthermore, exposed workers with the Glu/Glu genotype had high tumor markers levels. There was a significant increase in levels of BPDE-Alb adducts in workers carrying A1AT mutant allele. Moreover, workers with mutant A1AT genotype had significantly high tumor markers (SCCAg and CCNB1) levels. CONCLUSION: Therefore, we conclude that aluminum workers may be at a potential risk of lung cancer development due to PAHs exposure. Although PAHs concentrations in air were within the permissible limits, yet evidence of DNA damage was present as expressed by high BPDE-albumin adduct level in exposed workers. Also, elevation of tumor markers (SCCAg and CCNB1) in exposed workers points to the importance of periodic biological monitoring of such workers to protect them from cancer risk.

Impact of mannose-binding lectin gene polymorphism on lung functions among workers exposed to airborne Aspergillus in a wastewater treatment plant in Egypt.

In this study, the risk of Aspergillus (Asp.) positivity and its respiratory health impacts on wastewater treatment plant (WWTP) workers were studied. In addition, it identified the geno-susceptibility role of mannose-binding lectin 2 (MBL2) gene polymorphisms and the mannose-binding lectin (MBL) serum levels on the pulmonary functions of the Asp.-positive workers. Pulmonary function tests (PFTs) were performed for 89 workers from a selected WWTP, after exclusion of the smokers. Molecular identification of Asp. blood positivity was done by 18S rRNA sequencing. Determination of MBL2 gene polymorphism and estimation of MBL serum levels were done. PFTs revealed abnormalities in 49.2% of the workers. Asp. was positive in 42.5% of the workers with different species. Among the Asp.-positive workers, 6.5% of the workers were with obstructive PFTs, 12.9% with restriction, and 22.6% with combined PFT abnormalities. MBL2 genotyping showed that wild genotype AA was common (68.5%) among Asp.-positive workers compared to the other genotypes. This allele, whether homozygous or heterozygous, was significantly associated with decline in PFTs of the exposed workers. MBL serum levels were significantly lower in workers with obstructive, restrictive, and combined PFT abnormalities compared to those with normal PFTs, and in the workers with Asp.-positive species than the Asp.-negative workers. Moreover, it was significantly lower in workers with Asp. fumigatus compared to that in the workers with other Asp. species, and in the Asp.-positive workers with homozygous or heterozygous A allele compared to that in the Asp.-positive workers with homozygous B allele. Working in a WWTP can be associated with impaired PFTs due to exposure to airborne fungi. MBL2 genotyping showed that Asp.-positive workers with homozygous or heterozygous A allele were at risk to develop decline in their PFTs.

18S rRNA gene sequencing for environmental aflatoxigenic fungi and risk of hepatic carcinoma among exposed workers.

Aspergillus exposure causes an increase in aflatoxin (AF) levels among exposed workers thereby increasing their risk of developing hepatocellular carcinoma (HCC). This study attempted to determine the presence of airborne aflatoxigenic fungi in environment of waste water treatment plant (WWTP); and study the hepatic cancer risks among exposed workers, emphasizing the role of glutathione S-transferases (GST) gene polymorphism protecting against the risk of hepatic cancer development due to exposure to AFs. The study isolated and identified different Aspergillus species producing AFs in air samples from WWTP sites using 18S ribosomal ribonucleic acid (18S rRNA) gene sequencing technique. GST gene polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A significant increase in blood AF levels was found among WWTP exposed workers. The occurrence of GSTT1& M1 gene polymorphism in 6% of the workers was accompanied by significant decrease in the levels of AFs and alpha fetoprotein (AFP). In conclusion, Aspergillus-producing AFs were found in air of WWTP. Continuous exposure to AF-producing fungi caused elevated AF-levels in exposed workers. However only workers with heterozygous GSTT1& M1 genotypes can detoxify AFs, thereby decreasing the risk of HCC development among exposed workers.

Role of antioxidant supplementation in oxidant/antioxidant status and hepatotoxic effects due to aflatoxin B1 in wheat miller workers.

Background Aflatoxin B1 (AFB1) is classified as a Group I carcinogen. A Previous study found that oxidative stress from the metabolism of AFB1 induced hepatotoxic effects in wheat miller workers. Zinc and vitamin C may play a significant role in the activation of detoxification and overcoming the oxidative stress of AFB1. Objectives A prospective clinical trial was designed to evaluate the role of zinc and vitamin C oral supplementation on the oxidant-antioxidant status and the hepatotoxic effects of AFB1 in wheat miller workers. Methods Liver enzymes (ALT, AST, ALP, and GGT), P53 protein, malondialdehyde (MDA), glutathione S transferase (GST), Superoxide dismutase (SOD), zinc and vitamin C were estimated in 35 wheat miller workers before and after zinc and vitamin C supplementation for 1 month. Results The results revealed that zinc and vitamin C were significantly increased after the one-month supplementation, while liver enzymes (AST, ALP, and GGT), MDA, and GST of the workers were significantly decreased. SOD and P53 were also decreased but not to a significant level; SOD was decreased in 56% and P53 was decreased in 58% of the total workers. Conclusions Zinc and vitamin C oral supplementation for 1 month had an ameliorative effect on the hepatotoxicity of AFB1 in wheat miller workers, through decreasing MDA, SOD, and GST levels that in turn led to an improvement in their liver enzymes. Further study on a larger scale is needed to confirm these results.

Effect of dietary antioxidant supplementation (Cuminum cyminum) on bacterial susceptibility of diabetes-induced rats.

Diabetic patients are at risk of acquiring infections. Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Diabetes causes generation of reactive oxygen species that increases oxidative stress, which may play a role in the development of complications as immune-deficiency and bacterial infection. The study aimed to investigate the role of a natural antioxidant, cumin, in the improvement of immune functions in diabetes. Diabetes was achieved by interperitoneal injection of streptozotocin (STZ). Bacterial infection was induced by application of Staphylococcus aureus suspension to a wound in the back of rats. The antioxidant was administered for 6 weeks. Results revealed a decrease in blood glucose levels in diabetic rats (p < 0.001), in addition to improving immune functions by decreasing total IgE approaching to the normal control level. Also, inflammatory cytokine (IL-6, IL-1ß and TNF) levels, as well as total blood count decreased in diabetic rats as compared to the control group. Thus, cumin may serve as anti-diabetic treatment and may help in attenuating diabetic complications by improving immune functions. Therefore, a medical dietary antioxidant supplementation is important to improve the immune functions in diabetes.

Effect of occupational exposure to aflatoxins on some liver tumor markers in textile workers.

BACKGROUND: In a study of textile workers, the effects of occupational exposure to cotton dust-with possible exposure to aflatoxin-on levels of some liver tumor biomarkers were explored. METHODS: The study included 58 textile workers and 64 controls. Skin prick tests, urinary Aflatoxin M1 (AFM1) and the tumor biomarkers (alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), insulin-like growth factors (IGF-1) were measured. RESULTS: Positive reactants to Aspergillus niger, Aspergillus flavus, and cotton dust were significantly higher in pre-spinning (14.3%, 28.6%, and 28.6%, respectively) and spinning workers (25.0%, 33.3%, and 25.0%, respectively) compared to controls (4.7%, 7.8%, and 3.1%, respectively). Urinary AFM1 was significantly higher in the pre-spinning, spinning, and weaving groups compared to controls (554.2 ± 346.2 pg/ml, 459.1 ± 781.6 pg/ml, 296.5 ± 336.5 pg/ml and 68.5 ± 136.8 pg/ml, respectively). We found a highly significant increase in levels of serum AFU in textile workers, compared to the control group. CONCLUSION: Exposure to fungi had a significant effect on AFM1 measurements and tumor biomarkers, especially in allergic textile workers (with the exception of the arginase biomarker), though results were generally within normal limits.

Aspergillus hazardous problem in ceramic workers.

Ceramic workers are at a high risk of developing respiratory problems as they are exposed to high levels of respirable dust containing silica and high microbial counts, including high Aspergillus counts. The aim of the study was to study the percentage of ceramic workers with positive Aspergillus (A.) through polymerase chain reaction (PCR) and specific IgE (sIgE) for the different Aspergillus species. PCR and specific IgE (sIgE) for the different Aspergillus species (A. flavus, A. fumigatus and A. niger) were estimated in 40 ceramic workers and 56 control subjects. Results revealed that 32.5% of the workers' sputum was PCR positive for Aspergillus. About 69.2% of them were A. flavus positive, 15.4% A. niger positive, 7.7% A. fumigatus positive and 7.7% A. flavus and A. fumigatus positive. The percentage change in sIgE for A. fumigatus between the workers and their controls was over 100%, while less than 50% for the other two species. The sIgE levels for the three Aspergillus species were not significantly correlated with the duration of exposure. Fungal exposure could be considered potential hazardous problem in ceramic industry. There were no significant correlations between the duration of exposure and the sIgE for the different Aspergillus species.