The effects of treatment with cyclophosphamide and methylprednisolone on expression of endothelin-1 in unilateral instillation of paraquat-induced pulmonary fibrosis in guinea pigs

Ra Lee So Ra Lee, Cheol Jeong Hye Cheol Jeong, Kyu Kim Kyung Kyu Kim, Youb Lee Sang Youb Lee, Hyung Lee Sin Hyung Lee, Youn Cho Jae Youn Cho, Jeong Shim Jae Jeong Shim, Ho In Kwang Ho In, Sang Choi Jong Sang Choi, Hwa Yoo Se Hwa Yoo, Ho Kang Kyung Ho Kang

Research output: Contribution to journalArticle

Abstract

Background: The herbicide paraquat can cause severe lung injury and fibrosis in experimental animals. In this study we have investigated the changes in lung endothelin-1(Et-1) levels and immunohistochemical localization in relation to treatment with cyclophosphamide and methylprednisolone in paraquat induced pulmonary fibrosis in guinea pigs. Material and methods: 29 male Hartley guinea pigs were divided into 4 groups. Group I was normal control. Paraquat was instilled into the lung of guinea pig of group II, III and IV unilaterally. Group II was treated with cyclophosphamide and methylprednisolone. Group III was treated with methylprednisolone. Group IV was not treated. The degree of fibrosis was evaluated by H-E stains and Masson's trichrome stains and cell activity was assessed by Et-1 immunohistochemical stains. Statistical evaluation was performed using the Kruskawallis one-way analysis. Results: Paraquat induced an increase in numbers of fibroblasts and total amount of lung collagen in Group IV compared to the normal controls. There was no significant difference in total numbers of fibroblasts between any of paraquat instilled groups, but there was significant increase in total amount of collagen in Group IV compared to group II and III (p<0.05). The treatment of cyclophosphamide and methylprednisolone suppressed the growths of both fibroblasts and collagen, but this suppression was stastically significant only in the case of collagen. Et-1 immunoreactivities of bronchial epithelium, type II pneumocytes, endothelial cells and fibroblast in group II and III were decreased compared to those in group IV. Conclusion: These results demonstrate that Et-1 is an important contributing factor in the pathogenesis of pulmonary fibrosis. Et-1 is synthesized and released by bronchial epithelium, Type II pneumocyte, endothelial cells, alveolar macrophages and fibroblasts. Especially they are associated with alveolar macrophage and fibroblasts. We conclude that combined therapy of cyclophosphamide and methylprednisolone are more effective in the control of Et-1 expression and collagen deposition.

Original languageEnglish
Pages (from-to)775-785
Number of pages11
JournalTuberculosis and Respiratory Diseases
Volume46
Issue number6
Publication statusPublished - 1999 Jan 1

Keywords

  • Cyclophosphamide
  • Endothelin-1
  • Methylprednisolone
  • Paraquat
  • Pulmonary fibrosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Cite this

So Ra Lee, R. L., Hye Cheol Jeong, C. J., Kyung Kyu Kim, K. K., Sang Youb Lee, Y. L., Sin Hyung Lee, H. L., Jae Youn Cho, Y. C., Jae Jeong Shim, J. S., Kwang Ho In, H. I., Jong Sang Choi, S. C., Se Hwa Yoo, H. Y., & Kyung Ho Kang, H. K. (1999). The effects of treatment with cyclophosphamide and methylprednisolone on expression of endothelin-1 in unilateral instillation of paraquat-induced pulmonary fibrosis in guinea pigs. Tuberculosis and Respiratory Diseases, 46(6), 775-785.