Fructose-1,6-Bisphosphate Prevents Bleomycin-Induced Pulmonary Fibrosis in Mice and Inhibits the Proliferation of Lung Fibroblasts

• Published in: Inflammation 2018-10, Vol.41 (5), p.1987-2001
• Main Authors: Jost, Renan Trevisan, Dias, Henrique Bregolin, Krause, Gabriele Catyana, de Souza, Rodrigo Godinho, de Souza, Tássia Rezende, Nuñez, Nailê Karine, dos Santos, Fernanda Greinert, Haute, Gabriela Viegas, da Silva Melo, Denizar Alberto, Pitrez, Paulo Márcio, da Silva, Vinicius Duval, Donadio, Márcio Vinícius Fagundes, de Oliveira, Jarbas Rodrigues
• Format: Article
• Language: English
• Subjects: Alveoli; Animals; Biomedical and Life Sciences; Biomedicine; Bleomycin; Bleomycin - pharmacology; Body weight; Body weight loss; Bronchus; Cancer; Cell culture; Cell Line; Cell Proliferation - drug effects; Cellular Senescence - drug effects; Collagen; Embryo fibroblasts; Embryos; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - pathology; Fibrosis; Fructose; Fructose-1,6-diphosphate; Fructosediphosphates - pharmacology; Fructosediphosphates - therapeutic use; Glycolysis; Humans; Immunology; Immunomodulation; Inflammation; Interferon; Internal Medicine; Lung - pathology; Lung diseases; Mice; Mice, Inbred C57BL; Original Article; Pathology; Pharmacology/Toxicology; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - prevention & control; Respiratory function; Rheumatology; Senescence; Survival Rate; Tumors; Weight Loss - drug effects
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-018-0842-3

Pulmonary fibrosis is a specific form of interstitial pneumonia. In addition to the idiopathic cause, it may be caused by drugs such as bleomycin (BLM)—used in the treatment of tumors. Fructose-1,6-bisphosphate (FBP) is a high-energy endogenous glycolytic compound that has antifibrotic, anti-inflammatory, and immunomodulatory effects. The aim of this study was to investigate the effects of FBP on both BLM-induced pulmonary fibrosis in mice and in a human embryonic lung fibroblast (MRC-5) culture system. C57BL/6 mice were divided into four groups: control, FBP, BLM, and BLM plus FBP. A single dose of bleomycin (7.5 U/kg) was administered intratracheally, and survival, body weight, Ashcroft score, and histological analysis were evaluated. Pulmonary function and bronchoalveolar lavage fluid (BALF) were also evaluated after a single dose of bleomycin (1.2 U/kg—intratracheally). Treatment with FBP (500 mg/kg) was given on day 0 intraperitoneally. Fibroblasts (MRC-5 cells) were used to access the effect of FBP in vitro . In vivo , FBP increased the survival rate and reduced body weight loss (BLM vs. BLM plus FBP— p