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Occupational Health - Public Health Poster Session






Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References




Discussion
Board

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Isocyanates: Influence on Characteristics of Immunity Homeostasis and Oxidation-Reduction Homeostasis.


Contact Person: Alexander V. Shabunin (ipz@sandy.ru)


Introduction

Isocyanates are chemicals that are widely used in manufacturing of polyurethanes (PU). PU are broadly applied in motor-car and aircraft construction, furniture manufacturing, sport equipment and other fields. Isocyanates possess high biological activity, they can evoke various disturbances of health condition and cause negative effect on bronchopulmonary and nervous systems, peripherical blood circulation, liver and kidneys. Bronchial asthma is on the first place among occupational diseases caused by isocyanates exposure. Protective role of oxidation-reduction and immune reactions in supporting human homeostasis is well known. At present time biochemical changes reflected disturbances of detoxification processes are considered as primary link in pathogenesis caused by environmental chemical factor, that lead to immune system disregulation [5]. Many investigators have come to conclusion that indexes of lipid peroxidation (LP), antioxidant protection (AP), immunity status (IS) are adequate criteria for evaluation of protective-adaptive systems status [3, 6]. Taking into consideration high biological activity of isocyanates and various changes induced by isocyanates in workers and experimental animals, it is expedient to study isocyanates influence on lipid peroxidation, antioxidant provision and immune status.

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Materials and Methods

Experimental tests were performed in 97 white rats (weight 180-200 g) by TDI inhalation exposure at concentration: 0.5 0.07 mg/m3 and 0.05 0.03 mg/m3 (10 MAC and MAC). The rats were investigated at 7th, 14th and 30th days at TDI exposure and after 30 days of restoring period. Control group of rats was also investigated, but they were not exposed to TDI. To evaluate immune status indexes we performed determination of mass and cellularity of immune organs (thymus and spleen); IgG level; R-proteins; lysozyme, absorption ability of neutrophils using phagocyte number (PhN). Malon dialdehyde (MDA) in erythrocytes and plasma [9], peroxidal hemolysis of erythrocytes [8], value of induced chemoluminescence (ind.CL)[l], activity of catalase [7], glutathion peroxidase (GP) and ceruloplasmin(CP) [4] were defined to characterise LP and AP. Clinical and immunological examination was performed in 117 workers exposed to TDI at concentration lower than MAC and up to 8 MAC. Blood lymphocytes number of their basic populations - T-lymphocytes (T-L) with calculation of high-avid cells (T-HAL), B-lymphocytes (B-L) were counted, as well as load tests with theophylline and levamisole were performed. Concentration of serum immunoglobulins - IgM, IgG, IgA; number of neutrophils and their absorption ability (PhN), metabolic activity at spontaneous and activated NST test; E-receptor(Er) expression were evaluated. Saliva immunity status was evaluated basing on levels of IgM, IgG, IgA, sIgA, and lysozyme with calculation of balance coefficient (AN). Allergic reactivity was studied by evaluation of basophils and eosinophils number, total serum IgE, intensity of spontaneous basophils degranulation test (BDT). The control group consisted of 60 practically healthy persons non-exposed to chemicals at work and in household. Results of the investigation were treated by using variation and correlation analysis and computer techniques.

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Results

Changes in various indexes of immunity were revealed by experiment (Fig. 1, 2). Increasing of spleen cellularity (at 7th day), IgG level, R-proteins (at 14th day) was shown in initial period at TDI concentration = 0.5 mg/m3 .

Figure 1

Immunological and biochemical indexes in rats exposed to TDI concentration 0.05 mg/m3

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Figure 2

Immunological and biochemical indexes in rats exposed to TDI concentration 0.5 mg/m3

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Decreasing of spleen cellularity was observed at 30th day with increased level of lysozyme and phagocyte absorption ability of neutrophils (PhN). Normalisation of IgG level, lysozyme and phagocyte absorption function of neutrophils was recorded in restoring period, but at same time there were higher R-protein level and higher thymus and spleen cellularity. TDI exposure at concentration of 0.5 mg/m3 led to increasing thymus and spleen cellularity in rats to 14th day and lysozyme activity increasing to 30th day, but in restoring period thymus cellularity increased. Changes in LP and AP processes were also revealed at TDI exposure at both concentrations. Increased indCL levels in erythrocytes and plasma; increased MDA content, especially in plasma, were observed at TDI concentration exposure = 0.5 mg/m3. Further indCL levels increasing, as well as decreasing of MDA level, catalase and GP activity were found at 14 day. Decreasing of indCL, catalase activity normalisation, catalase and GP activity increasing were noted after 30 days of the exposure. There was no normalisation in restoring period, but indCL and MDA levels in plasma were considerable. Increasing of indCL in plasma to 14 day and MDA content to 30 day were found at TDI concentration exposure = 0.05 mg/m3. Normalisation of all studied indexes occurred in restoring period. Changes in basic immunity indexes were established in persons occupationally exposed to TDI (Fig. 3).

Figure 3

Changes in immune status in workers exposed to TDI in comparison to control group (%)

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Cellular immunity functional disorders which consisted in deep (but mainly reversible) modification of T-L cell membrane and decreasing of T-HAL cells (most functionally active T cells) were noted in 50% cases. As to humoral immunity parameters - IgM, IgG decreasing levels with increasing of IgA and B-L was observed. Weakening of phagocytic and metabolic neutrophilic activity and strengthening of Er expression were found. Local immunity changes consisted in IgA, sIgA, lysozyme decreasing and IgG increasing that had led to disbalance of these factors and saliva protective properties. This disbalance consisted in increasing AN in 94% cases. Activation of blood basophil degranulation processes was a sign of worker allergization. It was observed in 17.5% of persons.

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Discussion and Conclusion

Humoral immunity activation against background of R-protein increasing was observed in initial period at TDI concentration exposure at 10 MAC. It was a result of cell autolysis in various organs and tissues due to unfavourable factor. Later on the depression of non-specific protection factors and some indexes of humoral immunity in presence of high R-protein level were seen. Together with decreasing of neutrophil absorption activity, it provided evidence that there was not possibility to eliminate homeostasis disorders by using phagocytosis of catabolic degradation products. Normalisation of the most changed indexes and some activation of cellular and humoral response took place in restoring period, which was a favourable sign. However, R-protein levels kept high, therefore it provided evidence that autolysis had continued. Air concentration of TDI at workplace at MAC level promoted only activation of some cellular and humoral immunity indexes and non-specific protection factors that was a favourable sign. At the same time increasing of plasma indCL and MDA level may be interpreted as prognostically unfavourable signs so far as the changes of protective systems may be a pathogenesis trigger due to chemical exposure. Thus, TDI effect on homeostasis of experimental animals at 1-10 MAC consisted in immune status changes (predominant activation of cellular, humoral immunity and non-specific protection; at 10 MAC level - depression of natural resistance mechanisms with high R-protein content). There also were the changes in LP (increasing CL of erythrocytes and plasma, MDA, peroxide hemolysis) and AP (phase changes of catalase activity, GP). Functional changes in cellular immunity (reverse modification of T-lymphocytes membrane), depression of some humoral immunity indexes - IgM, IgG production with increasing of IgA, B-L; various neutrophils function shifts - decreasing of absorption and metabolic activity with Er expression strengthening; disbalance of local immunity and allergization signs.

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References

1. Babenko GA, Gonskiy IaM., Antonik IM. et al. Biochemiluminiscence- Moscow (1983).-p.164-80.

2. Litovsakia AV, Oskerko EF, Egorova IV et al. Immunology 1997; (4): 53-7.

3. Maimulov VG, Baskovich GA, Dadali VA Metholologic aspects of biochemical research on the adaptational status in the human body Gig Sanit 1993;(10):61-4.

4. Mietgelschtedt AA Zhurn nevropat i psikhiatr 1984;(6):819.

5. Mukhambetova LKh, Petrova IV, Pinigin MA The status of the body protective systems in children in atmospheric pollution by grain dust Gig Sanit 1998;(2):3-5.

6. Tiunov LA Mechanisms of natural detoxification and antioxidant protection Vestn Ross Akad Med Nauk 1995;(3):9-13.

7. Beers RF, Siserl.W Bio. Chem 1952;195 (4):133-40.

8. Catcher GR, Raynor WR, Carrol PM Am J Clin Nutr 1994; 40(15): 1078-89.

9. Ishihara Y J. Clin Chem. 1978; 84.(4-2):l-9.

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Osipova, TV; Litovskaya, AV; Vasilieva, TV; Egorova, IV; Feklina, TIu; (1998). Isocyanates: Influence on Characteristics of Immunity Homeostasis and Oxidation-Reduction Homeostasis.. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/occupational/osipova0743/index.html
© 1998 Author(s) Hold Copyright