Influence of GSTM1, T1 genes polymorphisms on oxidative stress and liver enzymes in rural and urban pesticides-exposed workers.

Several studies discussed the relationship between the toxicity of organophosphates (OPs) and carbamates pesticides and oxidative stress which affects human health. This study aimed to evaluate the effects of pesticides on the induction of oxidative stress and hepatotoxicity. It was also focused on glutathione-S-transferase gene polymorphism in the modulation of these effects. In addition, the role of the educational level of exposed workers was studied. Acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), liver enzymes, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione S transferase (GST) were estimated at 100 pesticide-exposed workers (50 urban researchers (UE) and 50 rural sprayers (RE)), and 100 matched controls (50 urban controls (UC)and 50 rural controls (RC)). AChE and BuChE were decreased in RE and UE compared to RC. Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activity were elevated in UE and UC compared to the RE and RC. Alanine aminotransferase (ALT) was elevated in UE compared to RE. MDA in RE and UE showed elevation compared to RC. There was a significant reduction in the levels of GSH, GST, and GPx in UE compared to RE and RC. The most sensitive pesticide-induced hepatotoxicity group were exposed workers with the GSTT1 genotype. Within these workers, ALT and ALP were significantly correlated with MDA and inversely correlated with AChE and BuChE, while AST was inversely correlated with AChE and BuChE only in UE. Conclusion: GST gene polymorphisms appeared to have a significant role in workers' susceptibility to hepatotoxic effects due to occupational exposure to pesticides; GSTT1 was the most sensitive genotype.

Alteration in antioxidant status in slow and fast alleles of EPHX1 gene polymorphisms among wood workers.

Occupational wood dust exposure may be associated with various health effects, especially in wood industry. These effects may be due to inducing oxidative stress which is related to inflammations. Biochemical assessment of antioxidant enzyme activities illustrated role of oxidative stress (OS) on its depletion. Super oxide dismutase, glutathione peroxidase (GPx) and catalase (CAT) were analyzed in 50 exposed workers and 50 control subjects. Also, macrophage inflammatory protein-2 was assessed among these workers as it was produced upon dust exposure. Microsomal epoxide hydrolase (EPHX1) enzyme shared in the protective mechanism against wood dust oxidative stress. It plays a dual role in the metabolism of environmental pollutants, detoxification, and bioactivation. Gene polymorphisms of EPHX1 may be associated with variations in enzyme activity. Polymorphisms in exons 3 and 4 have resulted in either decreased (slow conjugating allele) or increased (fast conjugating allele) activity in vitro. We aimed to evaluate the associations between EPHX1 polymorphisms and change in antioxidant status (SOD, CAT, and GPx) among wood dust exposed workers. EPHX1 genotyping in exon 3 and exon 4 polymorphisms was carried out by PCR-RFLP. Our result shows a significant reduction in enzymatic antioxidants (SOD, CAT, and GPx) levels with significant rise in MIP-2 levels in worker group. Also, there are significant variations in SOD, CAT, and GPx levels as well as in MIP-2 in different genotypes of EPHX polymorphisms in exon 3 or 4 (specially in Hist-Hist genotypes in both exons). We can conclude an alteration in antioxidant status in both slow and fast allele of EPHX gene polymorphisms with release of MIP-2 protein in wood workers.

Association of microsomal epoxide hydrolase gene (fast genotype) with lung functions impairment in wood workers.

OBJECTIVES: Exposure to wood dust may lead to impairment of the lung functions. Microsomal epoxide hydrolase enzyme (EPHX1) was shown to take part in protection against oxidative stress. An alteration in enzyme activity might be associated with its gene polymorphisms. In vitro polymorphisms in exons 3 (His113Tyr) and 4 (Arg139His) lead to reduced activity (slow allele) and increased activity (fast allele). Macrophage inflammatory protein 2 (MIP-2) is produced in rat lung epithelial cells after exposure to fine particles. We aimed to investigate the associations between mEPHX1 polymorphisms (in exon 3 and 4) and lung function in furniture workers and assessment of MIP-2 effect. METHODS: Our study was performed on 70 wood dust exposed male workers and 70 matched normal controls subjects. Ventilatory function tests were measured by spirometer, MIP-2 was performed by ELISA methods and EPHX gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods for each participant. RESULTS: Significant reduction in forced vital capacity (FVC%) and forced expiratory volume in the first second (FEV1) levels in Tyr-Tyr and Tyr-Hist genotypes of EPHX (exon 3) was observed. Reduced peak expiratory flow (PEF) levels and significant rise in MIP-2 levels were detected in Tyr-Tyr genotype. While high significant reduction in FVC% and FEV1 levels were shown in different genotypes in exon 4. Significant rise was observed in MIP-2 levels in Hist-Hist genotype of exon 4. An increase in duration of exposure showed positive correlation with fall in ventilatory functions. CONCLUSIONS: It was concluded that in Hist139Arg of EPHX gene, fast genotype (Arg-Arg) was associated with impaired ventilatory functions.

Neurotoxicity of organic solvents with emphasis on the role of iron.

BACKGROUND: Exposure to organic solvents (OS) adversely affects different body systems, the central and peripheral nervous systems being the most susceptible ones. OBJECTIVES: This study investigated the role of iron in association with some neurotransmitters for diagnosis of neurotoxicity of OS. METHODS: The study included 90 workers, 50 occupationally exposed to OS and 40 representing control group. Blood samples were collected from the included subjects for determination of serum iron, total iron binding capacity (TIBC), serotonin and gamma-aminobutyric acid (GABA). RESULTS: Revealed reduction in serotonin level and serum iron. However, the elevation in GABA and TIBC was observed. The duration of exposure was significantly correlated with iron and serotonin while it was positively correlated with GABA and TIBC. CONCLUSIONS: Elevated GABA and TIBC with decreased serotonin and serum iron can be used as early diagnostic measures to detect the neurotoxic effects of OS.

Hepatotoxicity of aflatoxin B1 and its oxidative effects in wood dust Egyptian exposed workers.

The goal of the present study is to estimate the oxidative effects of AFB1 induced hepatotoxicity in furniture wood dust exposed workers. A cross-sectional comparative study was designed for comparing AFB1/albumin (AFB1/alb) levels and liver functions [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)], malondialdehyde (MDA), glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in 88 furniture workers and 78 controls not occupationally exposed to wood dust. The AFB1/Alb, AST, ALT, MDA, and GPx were significantly higher; while, CAT significantly reduced in workers compared with controls. There was a significant correlation between AFB1/Alb and MDA level with the liver enzymes among both groups. CAT was inversely correlated with AFB1/Alb and the liver enzymes, and GPx was inversely correlated with AST in the workers. It was concluded that wood dust exposure is associated with raised serum levels of AFB1 and oxidative stress.

Evaluation of the effect of serum cystatin-C and ACE I/D and ACE G2350A polymorphisms on kidney function among hypertensive sewage workers.

Cadmium (Cd) as nephrotoxicant metal exerts its potent effect mainly on renal tubules disturbing its functions. A cross-sectional study was conducted on 55 sewage workers occupationally exposed to Cd and 50 control subjects. The study aimed to assess the effect of low-level Cd exposure on blood pressure and renal function in terms of serum cystatin-C levels. The associations between genetic polymorphisms of ACEI/D and ACE G2350A and hypertension and tubular injury among workers were studied. We analyzed blood and urine Cd concentration (U-Cd), serum cystatin-C, ACE I/D polymorphisms, and ACE G2350A, and blood pressure was measured. Results recorded a significant rise in serum and U-Cd and cystatin-C levels in sewage workers compared with controls. Significant distribution in genotype frequency of ACE I/D and ACE G2350A gene was detected. An association in DD genotype of ACE I/D with a rise in serum and U-Cd was observed in workers. In wild type genotype GG of ACE G2350A gene, a significant rise in serum cystatin-C levels and diastolic pressure was found while in heterozygote genotype GA significant rise in U-Cd levels was detected. Also, the association of AA genotype of ACE G2350A gene with a significant rise in serum and U-Cd and cystatin-C levels was shown among workers compared with control groups. Our findings indicated an association of ACE DD polymorphism in conjugation with GG genotype of ACE2 with hypertension and tubular injury in sewage workers.

Assessment of YKL-40, lipid profile, antioxidant status, and some trace elements in benign and malignant breast proliferation.

Breast cancer is mainly the common form of cancer in women and is a leading cause of death worldwide associated with cancer. The objective of this study was to assess the possible association of lipid profiles (total cholesterol TC, low-density lipoprotein LDL, very-low-density lipoprotein VLDL, high-density lipoprotein HDL, non-HDL and triglyceride TG), Chitinase-3-Like Protein1 (YKL-40) and changes in the levels of certain trace elements (Cu, Mg, Fe, and Zn), antioxidant status (TAC) and nitric oxide (NO) in benign and breast cancer in Egyptian females population. For 56 females with a benign breast tumor, 58 females with breast cancer, besides 52 healthy controls, Serum lipid profile, YKL-40, TAC, NO, Cu, Fe, Zn, and Mg have been determined. Our results showed a significant difference in lipid profile and a significant increase in, YKL-40, NO, and iron in breast benign tumor and cancer patients compared to control one. Besides, there is a significant reduction in serum magnesium and TAC levels in the patients' group compared to the healthy group. There is also a significant correlation between serum YKL-40 level and TC, LDL-C, VLDL-C, non-HDL-C, and TG in the breast cancer group; although only YKL-40 and VLDL-C showed a significant positive correlation in benign tumor patients. It is recommended that non-HDL-cholesterol, TAC, and Mg be used as biomarkers for breast cancer and its progression.

Audiometric notch for the prediction of early occupational hearing loss and its association with the interleukin-1beta genotype.

OBJECTIVES: Noise-induced hearing loss (NIHL) is a frequent and irreversible industrial-health problem, the early diagnosis of which can prevent hearing deterioration, especially of speech frequencies. This study aimed to assess hearing impairment in workers occupationally exposed to noise. Audiometric notches and IL-1ß gene polymorphisms were evaluated. METHODS: The study included 98 workers employed in a textile factory. Pure-tone audiometric testing was conducted for all workers, using a manual pure-tone diagnostic audiometer, and the noise level was measured at four different work sites in a spinning section. IL-1ß gene polymorphism was determined using PCR-RFLP methods. RESULTS: Workers were exposed to a mean noise level of 105.5 dB. As many as 27.6% of them complained of tinnitus and the majority suffered from some degree of hearing loss in either ear, but none of them exceeded 60 dB. Audiometric notches were detected in either one or both ears. Only 28.6% of workers showed the absence of notches. The TT genotype of IL-1ß polymorphisms was dominant in 49% of the workers, whereas TC was predominant in 39.8% and CC in 11.2%. The CC genotype was associated with smoking (54.5%) and audiometric notches (100%). The IL-1ß genotype distribution showed no significant difference with or without tinnitus. CONCLUSION: This study showed an association between the CC genotype and smoking as well as audiometric notches in workers occupationally exposed to noise. Workers showing audiometric notches should be followed up regularly. Further studies are required to confirm the interrelationship amongst tinnitus, audiometric notches, and IL-1ß genotypes.

Early prediction of liver carcinogenicity due to occupational exposure to pesticides.

Several studies linked between pesticides exposure and development of liver cancer, through several mechanisms inform of genotoxicity, cytotoxicity, tumor promotion, immunotoxicity and hormonal actions. This study aimed to estimate novel biomarkers for early prediction of liver malignancy due to occupational exposure to pesticides in two groups of workers with different socioeconomic standard (highly educated urban researchers and low educated rural pesticides sprayers). This study included 50 urban researchers and 50 rural pesticides sprayers occupationally exposed to pesticides. They were compared with 50 non-exposed urban researchers and 50 non-exposed rural subjects. Several tumor biomarkers were estimated; P53 protein, Alfa fetoprotein (AFP), and Alpha-L-fucosidase (AFU). Additionally, telomerase enzyme activity, Relative telomere length (RTL), and DNA damage using comet assay were measured. Furthermore, the glutathione-S-Transferase (GST) gene polymorphisms were identified for both exposed groups. Statistical analysis revealed elevated level of tumor biomarkers among exposed subjects relative to control groups in spite of being within the normal range. Increase in the DNA damage was detected, with shortening of telomere length and decrease in telomerase enzyme activity in pesticides-exposed subjects compared to their controls. Most of these changes were related to the levels of butyrylcholinesterase. Subjects with GSTT1 genotype were suggested to be more susceptible to hepatic carcinogenicity. Telomere relative length and comets assay together with GST genes polymorphisms could be used as early predictors for liver cancer susceptibility among pesticides exposed workers.

Impact of occupational cadmium exposure on bone in sewage workers.

Cadmium (Cd) is one of the environmental risk factors for bone loss. The present study included 40 sewage workers occupationally exposed to Cd. Forty nonexposed men were included as a control group. Current smokers represented 65% and 47.5% of the exposed and control groups, respectively. The study aimed to investigate the hazard of occupational Cd exposure on bone health. This was achieved through measuring serum and urinary Cd, and calcium (Ca), in addition to serum osteoprotegerin (OPG) and estrogen receptor-α gene. Results showed significant elevation in serum Cd, OPG, and urinary Ca levels in the exposed compared to the controls. Bony aches and joint pain were more prevalent among the exposed workers. Serum and urinary Cd increased in exposed smokers relative to control smokers. Also, serum OPG levels showed significant rise among exposed smoker and nonsmoker compared to control smoker and nonsmoker groups. Serum Cd level increased significantly in PP and pp genotypes in exposed workers compared to controls, while elevated levels of serum OPG was observed in PP and Pp genotypes in exposed workers relative to controls. Urinary Cd exhibited significant rise in both PP and pp genotypes in exposed workers, while Ca excretion was elevated in pp genotype only. The study reflected an association of genetic predisposition and Cd exposure in progression of osteoporosis. Further research is needed to explain the mechanisms of Cd impact on bone. The role of smoking is important and hence smoking cessation programs are essential for sewage workers.

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.

Comparative Hepatotoxicity of Aflatoxin B1 among Workers Exposed to Different Organic Dust with Emphasis on Polymorphism Role of Glutathione S-Transferase Gene.

AIM: The study aimed to investigate effects of organic dust exposure from different sources on aflatoxin B1-albumin adducts (AFB1/Alb), and role of glutathione S-transferase (GST) gene polymorphism in hepatotoxicity of (AFB1) among exposed workers. MATERIAL AND METHODS: Liver enzymes, AFB1/Alb, and GST polymorphism were estimated in 132 wheat flour dust and 87 woods sawmill workers, and 156 controls. RESULTS: Results revealed that AFB1/Alb and liver enzymes were significantly elevated in exposed workers compared to controls, and were significantly higher in sawmill workers compared to flour workers. AFB1/Alb in flour and sawmill workers with GSTT1 and GSTM1&GSTT1 null genotypes were significantly higher than controls, and in sawmill workers with GSTM1&GSTT1 null than flour workers. Liver enzymes (ALT and AST) in sawmill workers were significantly higher than flour workers and controls in all GST polymorphism; except in GSTT1 polymorphism, where these enzymes were significantly higher in the two exposed groups than controls. CONCLUSIONS: In conclusion, organic dust exposure may cause elevation in AFB1/Alb and liver enzymes of exposed workers, and GST gene polymorphism plays an important role in susceptibility to hepatic parenchymal cell injury; except in workers with GSTT1&GSTM1 null genotype, gene susceptibility seemed to have little role and the main role was for environmental exposures.

Carcinogenic effects of aflatoxin B1 among wheat handlers.

BACKGROUND: Epidemiological studies have demonstrated that serum aflatoxin B1 (AFB1) is a hepatocarcinogenic mycotoxin and contributor to the high rate of hepatocellular carcinoma (HCC). The prevalence of liver cancer in Egypt is particularly worrisome. In a registry-based analysis of occupational risk for HCC, significant excesses were observed especially for grain mill workers. OBJECTIVE: The aim of this study was to assess the hepatic carcinogenicity of AFB1 in wheat handlers. METHODS: Serum AFB1/albumin (AFB1/Alb), alpha-fetoprotein (AFP), alpha-l-fucosidase (AFU), and arginase were estimated in exposed wheat handlers including millers and bakers. The control group was composed of non-occupationally exposed workers. RESULTS: AFB1/Alb and AFU were significantly higher among workers employed as bakers compared to mill workers and controls. Mill workers had higher levels of AFB1/Alb than the controls. AFB1/Alb, AFP, and AFU were all significantly higher and arginase was significantly lower among HCC cases compared to the other groups. There was a significant correlation between AFU and AFB1/Alb in bakers and between AFP and AFB1/Alb in HCC cases. Arginase was inversely correlated with AFB1/Alb in HCC cases. AFB1/Alb was significantly correlated with the duration of exposure in bakers. CONCLUSION: Wheat handlers exposed to Aspergillus flavus have a high risk of elevated serum AFB1/Alb levels and AFU.

Gastritis induced by Helicobacter pylori infection in experimental rats.

BACKGROUND: Gastritis, an inflammation of gastric mucosa, may be due to many pathological factors and infection, such as with Helicobacter pylori. The use of experimental models of gastritis is important to evaluate the biochemical changes and study chemotherapeutic intervention. In a previous study we demonstrated an acute gastritis model induced by iodoacetamide. AIMS: Our objective in this study was to evaluate a new gastritis model induced by H. pylori infection in experimental rats in terms of certain biomarkers in serum and mucosal tissues in addition to histopathological examination. METHODS: Gastritis was induced in 20 albino Wistar rats by H. pylori isolated from antral biopsy taken from a 49-year-old male patient endoscopically diagnosed as having H. pylori infection. Another ten rats were used as controls. Serum gastrin, pepsinogen I activity, interleukin-6 (IL-6) and gastric mucosal myeloperoxidase (MPO) activity and prostaglandin E(2) (PGE(2)) were measured. Immunostaining for inducible nitric oxide synthase (iNOS), nitrotyrosine and DNA fragmentation were used to further evaluate H. pylori-induced gastritis. RESULTS: Serum gastrin, IL-6, mucosal MPO activity, and PGE(2) demonstrated significant increases joined with a decreased serum pepsinogen I activity (P < 0.001). Immunohistochemistry demonstrated positive reaction for iNOS, nitrotyrosine and DNA fragmentation. CONCLUSIONS: Helicobacter pylori-induced gastritis models demonstrated massive oxidative stress and pronounced injury in mucosal tissue. Since our model in rats reflected the clinical picture of H. pylori infection, it can be considered as a consistent model to study chemotherapeutic intervention for this type of gastritis.