Oral Administration of Bosentan Attenuates the Bleomycin Induced Pulmonary Fibrosis in Mice - Volume 3, No.2, April, 2014 - IJLBPR
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Oral Administration of Bosentan Attenuates the Bleomycin Induced Pulmonary Fibrosis in Mice

Shanmuga Reddy Chilakapati1,2, Mamatha Serasanambati1, Jagadeeswara Reddy Kanala1, Pavan Kumar Manikonda1, and Damodar Reddy Chilakapati1
1. SugenLife Sciences Pvt Ltd, Tirupati, Andhra Pradesh, India, 517 505
2. Sri Venkateswara University, Deparment of Biochemistry, Tirupati, Andhra Pradesh, India, 517 502
Abstract—Idiopathic Pulmonary Fibrosis (IPF) is characterized by alveolitis with epithelial, endothelial damage leading to fibrosis. As signaling of endothelin-1 was involved in IPF, the effect of bosentan a non-specific endothelin receptor antagonist was determined in a mouse model of bleomycin induced pulmonary fibrosis. In the present study, mice were instilled with intra-tracheal instillation of bleomycin (0.05U) and were administered with bosentan at 100 mg/kg body weight. The treatment with bosentan significantly (p≤0.05) prevented bleomycin induced mortality and loss of body weight. On day 7, bosentan significantly (p≤0.05) attenuated bleomycin induced increase of total and differential inflammatory cell counts, total proteins, edema, MPO activity and inflammatory cell infiltration in lung tissue. The activities of superoxide dismutase and catalase were restored by bosentan treatment which lowered in bleomycin administered mice. Bosentan treatment significantly attenuated bleomycin induced increase in fibrosis score, collagen deposition and hydroxyproline levels. On day 21, treatment with bosentan significantly attenuated α-smooth muscle actin and collagen-I gene expression levels and matrix metalloproteinases 2 and 9 activities. The results revealed that bosentan exerted enhanced protection against bleomycin induced inflammation and fibrosis. 

Index Terms—pulmonary fibrosis, endothelin-1, bosentan, collagen

Cite: Shanmuga Reddy Chilakapati, Mamatha Serasanambati, Jagadeeswara Reddy Kanala, Pavan Kumar Manikonda, and Damodar Reddy Chilakapati, "Oral Administration of Bosentan Attenuates the Bleomycin Induced Pulmonary Fibrosis in Mice," International Journal of Life Sciences Biotechnology and Pharma Research, Vol. 3, No. 2, pp. 57-73, April 2014.
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