Ahmed Mohamed Kabel

Egypt

Repurposing itraconazole for mitigation of bleomycin-induced pulmonary fibrosis: Targeting the inflammatory cascade, oxidative stress, and autophagy

Ahmed M. Kabel 1,2, Abeer Elkhoely 3, Remon S. Estfanous 4, Majed Alrobaian 5, Hany M. Borg 6

1 National Drug Committee, Academy of Scientific Research and Technology, Cairo, Egypt
2 Pharmacology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
3 Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Egypt
4 Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Egypt
5 Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taif University, KSA
6 Physiology Department, Faculty of Medicine, Kafrelsheikh University, Egypt

Abstract

Background

Bleomycin (BLM) is an antitumor medication that had shown efficacy in the treatment of a wide range of malignant conditions. Pulmonary fibrosis which is frequently encountered during the course of bleomycin therapy may significantly decrease the efficacy of bleomycin in cancer therapy. This work investigated whether itraconazole has mitigating effects on BLM-induced pulmonary fibrosis and tried to explore the potential mechanisms that may underlie these effects.

Methods

In a rodent model of pulmonary fibrosis induced by BLM, the effect of different doses of itraconazole was explored at the biochemical, histopathological, and electron microscopic levels.

Results

Itraconazole dose-dependently exhibited significant effects on the pro-oxidant/ antioxidant balance, the inflammatory consequences, high-mobility group box 1/toll-like receptor-4 Axis, autophagy and nuclear factor kappa B/Nod-like receptor protein 3 inflammasome signaling and alleviated the histopathological, immunohistochemical, and electron microscopic perturbations induced by BLM in the pulmonary tissues.

Conclusions

Itraconazole may represent a promising drug that efficiently ameliorates the deleterious effects of BLM on the pulmonary tissues.