To evaluate the therapeutic effect of various drug combination in experimental pneumoconiosis, a total of 240 Spraque-Dawley was instilled intratracheally by 50 mg free silica or coal dust with 0.8 ml normal saline. In the control group, it was intratracheally instilled only dust at once, while from l1th week experimental groups were administered drug. Experimental groups were divided into 8 groups according to drug combination such as group treated with piperazine and aspirin, piperazine and allopurinol, piperazine and azathioprine, aspirin and allopurinol, aspirin and azathioprine, allopurinol and azathioprine, solumedrol, and solumedrol and cyclophosphamide. The duration of treatment was 10 weeks. All animals were killed at 20th week after dust instillation. We observed body weight at 20th week after dust instillation, the dry lung weight of left lung, total and differential cell count in bronchoalveolaT lavage (BAL) fluid. Leukotriene B4, tumor necrosis factor, and superoxide anion production from alveolar macrophage, amount of hydroxyproline in left lung, and the histopathologic examination in the right lung stained with hematoxylin-eosin and Masson's trichrome. The results were as follows 1. The dry weight of the left lung in groups of treated with piperazine combined with aspirin and piperazine combined with azathloprlne was significantly decreased compared to the control group in silica instilled group. 2. The total number of cells in BAL in all experimental groups of silica instilled group and group of pjperafine/azathioprine and aspirin/allopurinol of coal dust instilled group were significantly decreasea compared to each control group. 3. The silica instilled group, the percentage of macrophage in experimental group tended to be increased in comparison with the control group but neutrophil tended to be decreased. Among experimental group, in the group treated with solumedrol and solumedrol/cyclophosphamide, the percentage and number of Iymphocyte markedly increased compared to each control group 4. The amounts of Hydroxyproline in the group piperazine/allopurinol and piperazine/azathioprine of silica instilled group were markedly lower than in the control group. 5. The preduction of TNF from alveolar macrophage in experimental group tended to be decreased compared to each control group. 6. The pathologic score that quantified the pathologic finding in the right lung, in all exporimental groups except the treated with regimen contained solumedrol of silica instilled group was significantly decreased compared to control group. In coal dust instilled group, the pathologic score of the group treated with piperazine and allopurinol, aspirin and azathioprine, and allopurinol and azathioprine was markedly lower than control group. 7. We analyzed the indices for alveolitis and fibTosis. The most effective drug combination was treated with piperazine combined with azathioprine and piperazine combined with allopurinol.
Allopurinol ; Animals ; Aspirin ; Azathioprine ; Body Weight ; Cell Count ; Coal ; Cyclophosphamide ; Drug Combinations* ; Dust ; Hydroxyproline ; Leukotriene B4 ; Lung ; Macrophages ; Macrophages, Alveolar ; Methylprednisolone Hemisuccinate ; Neutrophils ; Pneumoconiosis* ; Silicon Dioxide ; Superoxides ; Therapeutic Irrigation ; Tumor Necrosis Factor-alpha