• 367 Views
  • 160 Downloads
Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 1, pp. 35-46
doi:10.11131/2017/101363

Evaluation of the Antifibrotic Effect of Serotonin Receptor Antagonists on Bleomycin Induced Pulmonary Fibrosis in Rats

Shimaa Z. Abd-Alla1, Samah M. Elaidy2, and Soha S. Essawy2

1Pharmacist, Suez Canal Teaching Hospitals, Ismailia, Egypt

2Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt


Copyright © 2017 Shimaa Z. Abd-Alla et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Idiopathic pulmonary fibrosis (IPF) is believed to be an epithelial-fibroblast disease. Activated epithelial cells are thought to release potent fibrogenic molecules and cytokines, such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta1 (TGF-β1), which in turn foster the transformation of fibroblasts into myofibroblasts and promote production of extracellular matrix molecules and so collagen deposition. Serotonin (5-hydroxy tryptamine, 5-HT) is an important mediator for lung fibrogenesis, with implication of 5-HT2A/B/C receptors. However, the antifibrotic effects of all 5-HT2 receptor subtypes versus 5-HT2A/C blockade is needing to be explored. So, the present study was conducted to evaluate the antifibrotic effects of mirtazapine (5-HT2A/C receptor blocker) and cyproheptadine (5-HT2A/B/C receptor blocker) on body weight changes, survival rates, the lung hydroxyproline and TGF-β1 levels as well as the histopathological changes of lung fibrosis, in bleomycin-induced rat pulmonary fibrosis. Eighty-eight adult rats were used and subdivided randomly into 11 groups. One normal control, five vehicle control groups and five groups with IPF that induced by intra-tracheal instillation of bleomycin alone (5mg/kg), or bleomycin and treated with either mirtazapine (15 mg/kg/day) or cyproheptadine (5 mg/kg/day) for 7 and 14 days. Oral treatment with either mirtazapine or cyproheptadine, significantly ameliorated losses in body weights, reduction in survival rates, lung hydroxyproline and TGF-β1 levels and the inflammatory effects in lungs induced by bleomycin. The mechanisms underlying these therapeutic effects could be dependent on the reduction of TGF-β1 actions as decreasing lung inflammation and production and deposition of collagen in fibrotic lung tissues.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 1, pp. 35-46
doi:10.11131/2017/101363

Evaluation of the Antifibrotic Effect of Serotonin Receptor Antagonists on Bleomycin Induced Pulmonary Fibrosis in Rats

Shimaa Z. Abd-Alla1, Samah M. Elaidy2, and Soha S. Essawy2

1Pharmacist, Suez Canal Teaching Hospitals, Ismailia, Egypt

2Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt


Copyright © 2017 Shimaa Z. Abd-Alla et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Idiopathic pulmonary fibrosis (IPF) is believed to be an epithelial-fibroblast disease. Activated epithelial cells are thought to release potent fibrogenic molecules and cytokines, such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta1 (TGF-β1), which in turn foster the transformation of fibroblasts into myofibroblasts and promote production of extracellular matrix molecules and so collagen deposition. Serotonin (5-hydroxy tryptamine, 5-HT) is an important mediator for lung fibrogenesis, with implication of 5-HT2A/B/C receptors. However, the antifibrotic effects of all 5-HT2 receptor subtypes versus 5-HT2A/C blockade is needing to be explored. So, the present study was conducted to evaluate the antifibrotic effects of mirtazapine (5-HT2A/C receptor blocker) and cyproheptadine (5-HT2A/B/C receptor blocker) on body weight changes, survival rates, the lung hydroxyproline and TGF-β1 levels as well as the histopathological changes of lung fibrosis, in bleomycin-induced rat pulmonary fibrosis. Eighty-eight adult rats were used and subdivided randomly into 11 groups. One normal control, five vehicle control groups and five groups with IPF that induced by intra-tracheal instillation of bleomycin alone (5mg/kg), or bleomycin and treated with either mirtazapine (15 mg/kg/day) or cyproheptadine (5 mg/kg/day) for 7 and 14 days. Oral treatment with either mirtazapine or cyproheptadine, significantly ameliorated losses in body weights, reduction in survival rates, lung hydroxyproline and TGF-β1 levels and the inflammatory effects in lungs induced by bleomycin. The mechanisms underlying these therapeutic effects could be dependent on the reduction of TGF-β1 actions as decreasing lung inflammation and production and deposition of collagen in fibrotic lung tissues.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 1, pp. 35-46
doi:10.11131/2017/101363

Evaluation of the Antifibrotic Effect of Serotonin Receptor Antagonists on Bleomycin Induced Pulmonary Fibrosis in Rats

Shimaa Z. Abd-Alla1, Samah M. Elaidy2, and Soha S. Essawy2

1Pharmacist, Suez Canal Teaching Hospitals, Ismailia, Egypt

2Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt


Copyright © 2017 Shimaa Z. Abd-Alla et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to Cite this Article

Shimaa Z. Abd-Alla, Samah M. Elaidy, and Soha S. Essawy, “Evaluation of the Antifibrotic Effect of Serotonin Receptor Antagonists on Bleomycin Induced Pulmonary Fibrosis in Rats,” Egyptian Journal of Basic and Clinical Pharmacology, Vol. 7, Issue 1, pp. 35-46, 2017. doi:10.11131/2017/101363