Serum Clara-Cell Protein and β₂-Microglobulin as Early Markers of Occupational Exposure to Nitric Oxides

Abstract

Biochemical effects of NOx on 60 workers (both genders) of nitric acid production were studied. The control group consisted of 61 nonexposed people employed elsewhere in the plant. Although the actual threshold limit value–time weighted averages (TLV-TWA) were not exceeded in the specific conditions of our study, the subjects were exposed to NO_bm2 and NO during several exposure episodes with peak maximal concentrations of 140 ppm and 515 ppm, respectively. Additional cross-week evaluation of several biochemical biomarkers in 15 NOx-exposed workers from one shift was performed. The objective of the study was to evaluate the value of serum Clara-cell protein (CC16) as a marker of bronchoalveolar epithelium activity. Antioxidant status was assessed by measuring activity of enzymes: glutathione peroxidase (GSH-Px), ceruloplasmin (Cp) in plasma, or superoxide dismutase (SOD), gluthatione S-transferase (GST), and nonenzymatic α-tocopherol in erythrocytes and thiobarbituric acid-reactive substances (TBARS) in plasma. Serum hyaluronic acid (HA) determining the connective tissue matrix status of airways, and β₂-microglobulin in serum (β₂M-S) and urine (β₂M-U) as a marker of renal function in occupational exposure to NOx were also employed. Exposure to NOx initiates peroxidative chain depleting of lipoprotein pool (α-tocopherol) in blood. Serum CC16 levels in NOx-exposed workers were found to be closely connected with α-tocopherol content. In NOx-exposed workers, the β₂M-S level was significantly higher than in the nonexposed ones, with the exception of smokers. Results of the cross-week study confirm cumulative systemic effects of NOx on several examined biomarkers. SOD and GST were found to be depleted. A transient higher level of HA after a 5-d shift significantly inversely correlated with CC16 level. The data imply that NOx-depleted levels of CC16 are detectable already after an 8-h shift. Our results demonstrate that even low NOx human exposure can cause characteristic changes in bronchiolar epithelium cells and renal effects. Serum CC16 level, although a nonspecific marker, was lowest in NOx-exposed subjects. The most sensitive parameters in exposed workers were β₂M-S and α-tocopherol. Spirometric assessment was not useful to describe low occupational exposure to NOx. In studying the effects of NOx on biomarkers, it is essential to carefully select suitable time of sampling. Screening of CC16, β₂M-S, and α-tocopherol can be successfully employed for biological monitoring of exposure to NOx.

Notes

The Strategic Governmental Program on Health Protection and Safety at Work (Chief Coordinator: Central Institute for Labour Protection) supported this study (number SPR 04.10.14). Thanks are due to A. Kubiak for her participation in technical procedures, and M. W. Sobala for the statistical analysis.