Effects of oxidative stress and NF-kappaB levels in peripheral blood mononuclear cells on development of silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the change of indicators of oxidative stress in serum and NF-kappaB in peripheral blood mononuclear cells of patients with silicosis, and explore the mechanism of the development of silicosis.</p><p><b>METHODS</b>The subjects were divided into (1) 200 workers exposed to SiO2 for at least 1 years in a foundry served as the dust-exposure group; (2) 130 cases with silicosis (I phase silicosis 64 cases, II phase 46 cases III phase 20 cases) served as the silicosis group; (3) 32 cases with 0+ phase silicosis in the foundry served as the observed group,(4)100 subjects from a hotel served as the control group. The serum including superoxide dismutase (SOD), nitric oxide (NO), serum glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), nitric oxide synthase (NOS), lipid malondialdehyde (MDA) and NF-kappaB protein levels in peripheral blood mononuclear cells were determined, respectively.</p><p><b>RESULTS</b>Compared with the control group, NO levels in dust-exposed group and silicosis group significantly increased, and SOD decreased significantly (P < 0.05 or P < 0.01). Compared with the control group and dust-exposed group, T-AOC, NOS, MDA levels in silicosis group significantly increased (P < 0.05 or P < 0.01). GSH-Px in dust-exposed group and silicosis group were (231.164 +/- 36.484) and (270.469 +/- 39.228)U/ml, respectively which were significantly than that [(223.360 +/- 46.838) U/ml] in control group (P < 0.05 or P < 0.01), and there was significant difference of GSHPx between the silicosis group and the dust-exposed group significantly (P < 0.01) . GSH-Px level [(290.750 +/- 39.129) U/ml] in III phase silicosis group were significantly higher than those [(256.906 +/- 21.41) and (259.594 +/- 34.79) U/ml] in observation group and I phase silicosis group (P < 0.05). NF-kappaB levels [(72.06 +/- 9.12) and (85.25 +/- 11.64) ng/L] in dust-exposed group and silicosis group were significantly higher than that [(59.71 +/- 9.27) ng/L] in control group (P < 0.01), and there was significant difference of between the silicosis group and the dust-exposed group (P < 0.01). There was a positive correlation between serum GSH-Px level and the silicosis stages (r = 0.507, P < 0.01). Also there was a positive correlation between NF-kappaB level and silicosis stages, age, GSH-Px or NO levels (r = 0.376, 0.243, 0.233, 0.221, P < 0.01).</p><p><b>CONCLUSION</b>The imbalance of oxidative and anti-oxidation system and the activation of NF-kappaB are related with the occurrence and development of silicosis. The monitoring of oxidative stress indicators and NF-kappaB is beneficial to the prediction and prognosis assessment of silicosis.</p>

Associations of Blood Lead Levels, Kidney Function, and Blood Pressure with delta-Aminolevulinic Acid Dehydratase and Vitamin D Receptor Gene Polymorphisms.

The association of lead toxicity with delta -aminolevulinic acid dehydratase (ALAD) and vitamin D receptor gene polymorphisms was examined in 216 workers occupationally exposed to lead. Urinary N-acetyl- beta-glucosaminidase (UNAG) activity and albumin concentration, adjusted by creatinine, were measured as biomarkers of nephrotoxicity. Genotyping was performed using polymerase chain reaction and restricted fragment length polymorphisms. Blood pressure and blood and urinary lead concentrations were measured. No statistically significant difference in blood lead concentrations was observed with the ALAD genotype, although the geometric mean of blood lead concentrations was higher in battery workers with the ALAD-12 genotype (50.95 mug/dL) than in workers with the ALAD-11 genotype (42.95 mug/dL). Battery workers with the vitamin D receptor (VDR)-B allele had higher mean blood lead concentrations (60.54 mug/dL) than did the workers with the VDR-bb genotype (51.65 mug/dL) (p <. 05) . Based on multiple linear regression analysis, the VDR genotype was associated with a blood lead level (p <. 021). The ALAD genotype was associated with a urinary lead level (p <. 009). Workers with the ALAD-12 genotype who also had blood lead concentrations equal to or greater than 40 mug/dL had higher UNAG activity (4.17 U/mmol.Cr) than the workers with the ALAD-11 genotype (1.27 U/mmol.Cr) (p =. 06). Compared with workers with the VDR-bb genotype, workers with the VDR-B allele had higher systolic blood pressure when the blood lead level was equal to or greater than 40 mug/dL (133.06 +/- 19.19 mmHg versus 123.12 +/- 15.69 mmHg, p =. 01). Lead workers with ALAD-12 had larger elevations in UNAG activity and increasing blood lead concentrations compared to lead workers with the ALAD-11 genotype. Lead workers with the VDR-B allele had greater elevations in systolic blood pressure and higher blood lead levels than did workers with the VDR-bb genotype. In summary, the ALAD-2 and VDR-B alleles may modify lead absorption and toxicity.