Flavocoxid Improves Bleomycin-Induced Respiratory Dysfunction and Pulmonary Fibrosis; In vitro Study

Marwa Salah Zaghloul; Ramy Ahmed Abdel-Salam; Eman Said; Ghada Mohamed Suddek; Hatem Abdel-Rahman Salem

Authors

Marwa Salah Zaghloul Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt.
Ramy Ahmed Abdel-Salam Department of Pathology, Faculty of Medicine, Mansoura University, 35516, Mansoura, Egypt.
Eman Said Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt.
Ghada Mohamed Suddek Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt.
Hatem Abdel-Rahman Salem Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt.

Keywords:

Bleomycin, flavocoxid, Nrf2, HO-1, TNF-α, TGF-β1

Abstract

Pulmonary fibrosis; a progressive and fatal lung disorder is a common interstitial lung disease affecting millions of individuals worldwide with a mean survival time of about 3 years. It has been reported to be the most serious side effect observed with bleomycin's (BLM) use as a chemotherapeutic agent. Flavocoxid is a potent anti-inflammatory and anti-oxidant agent. In the current study, flavocoxid has been investigated for its ability to ameliorate BLM-induced pulmonary fibrosis, respiratory and vascular dysfunction in rats. BLM (5 mg/kg) was instilled intra-tracheally and flavocoxid was administered (20 mg/kg) orally for 5 weeks; one week pre- and 4 weeks post BLM instillation. Flavocoxid administration significantly decreased lung contents of Nrf2, HO-1, TLR4, TNF-α, TGF-β1. Moreover, flavocoxid successfully restored vascular response to Kcl, PE and carbacol and tracheal response to carbacol. In conclusion; flavocoxid ameliorated BLM-induced pulmonary fibrosis and improved respiratory functions and can be proposed to be a potential effective therapeutic agent for management of pulmonary fibrosis.